Influenza vaccine

{{See also|Timeline of vaccines}}

Vaccines are used in both humans and non-humans. The human vaccine is meant unless specifically identified as a veterinary, poultry, or livestock vaccine.

During the worldwide Spanish flu pandemic of 1918, "Pharmacists tried everything they knew, everything they had ever heard of, from the ancient art of bleeding patients, to administering oxygen, to developing new vaccines and serums (chiefly against what we call Hemophilus influenzae{{snd}}a name derived from the fact that it was originally considered the etiological agent{{snd}}and several types of pneumococci). Only one therapeutic measure, transfusing blood from recovered patients to new victims, showed any hint of success."{{cite book |author=Institute of Medicine | veditors=Knobler SL, Mack A, Mahmoud A, Lemon SM |title=The Threat of Pandemic Influenza: Are We Ready? Workshop Summary |publisher=The National Academies Press|page=62 |year=2005 |pmid=20669448 |doi=10.17226/11150 |isbn=978-0-309-09504-4 }}

In 1931, viral growth in embryonated hens' eggs was reported by Ernest William Goodpasture and colleagues at Vanderbilt University. The work was extended to the growth of influenza virus by several workers, including Thomas Francis, Jonas Salk, Wilson Smith, and Macfarlane Burnet, leading to the first experimental influenza vaccines.Plotkin, S.L. and Plotkin, S.A. "A short history of vaccination". In: Vaccines, Stanley A. Plotkin, Walter A. Orenstein, Paul A. Offit, eds. Elsevier Health Sciences, 2008, pp. 6–7. In the 1940s, the US military developed the first approved inactivated vaccines for influenza, which were used during World War II.Artenstein, A. W. "Influenza" In: Vaccines: A Biography, Andrew W. Artenstein, ed. pp. 191–205. Hens' eggs continued to be used to produce virus used in influenza vaccines, but manufacturers made improvements in the purity of the virus by developing improved processes to remove egg proteins and to reduce systemic reactivity of the vaccine.{{cite journal | vauthors = Hampson AW | title = Vaccines for pandemic influenza. The history of our current vaccines, their limitations and the requirements to deal with a pandemic threat | journal = Annals of the Academy of Medicine, Singapore | volume = 37 | issue = 6 | pages = 510–17 | date = June 2008 | doi = 10.47102/annals-acadmedsg.V37N6p510 | pmid = 18618064 | s2cid = 17102174 | doi-access = free }} In 2012, the US Food and Drug Administration (FDA) approved influenza vaccines made by growing virus in cell cultures,{{cite journal |vauthors=Milián E, Kamen AA |title=Current and emerging cell culture manufacturing technologies for influenza vaccines |journal=Biomed Res Int |volume=2015 |page=504831 |date=2015 |pmid=25815321 |pmc=4359798 |doi=10.1155/2015/504831 | doi-access = free | title-link = doi }}{{cite web | url=https://www.cdc.gov/flu/prevent/cell-based.htm | title=Cell-Based Flu Vaccines | publisher=U.S. Centers for Disease Control and Prevention (CDC) | date=October 11, 2019 | archive-url=https://web.archive.org/web/20191202213512/https://www.cdc.gov/flu/prevent/cell-based.htm | archive-date=December 2, 2019 | url-status=live | access-date=December 2, 2019}} {{PD-notice}} and influenza vaccines made from recombinant proteins were approved in 2013.{{cite press release | url = https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm335891.htm | title=FDA approves new seasonal influenza vaccine made using novel technology | date = January 16, 2013 | archive-url=https://web.archive.org/web/20130518014553/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm335891.htm | archive-date=May 18, 2013 | publisher=U.S. Food and Drug Administration (FDA)}} {{PD-notice}}

The egg-based technology for producing influenza vaccine was created in the 1950s.{{cite journal | vauthors = Osterholm MT | title = Preparing for the next pandemic | journal = The New England Journal of Medicine | volume = 352 | issue = 18 | pages = 1839–42 | date = May 2005 | pmid = 15872196 | doi = 10.1056/NEJMp058068 | citeseerx = 10.1.1.608.6200 | s2cid = 45893174 }} In the US swine flu scare of 1976, President Gerald Ford was confronted with a potential swine flu pandemic. The vaccination program was rushed, yet plagued by delays and public relations problems. Meanwhile, maximum military containment efforts succeeded unexpectedly in confining the new strain to the single army base where it had originated. On that base, several soldiers fell severely ill, but only one died. The program was canceled after about 24% of the population had received vaccinations. An excess in deaths of 25 over normal annual levels as well as 400 excess hospitalizations, both from Guillain–Barré syndrome, were estimated to have occurred from the vaccination program itself, demonstrating that the vaccine itself is not free of risks.{{cite web|url=http://www.haverford.edu/biology/edwards/disease/viral_essays/warnervirus.htm|archive-url=https://web.archive.org/web/19991009112042/http://www.haverford.edu/biology/edwards/disease/viral_essays/warnervirus.htm|archive-date=October 9, 1999|title=Swine Flu Epidemics|date=October 9, 1999}} In the end, however, even the maligned 1976 vaccine may have saved lives. A 2010 study found a significantly enhanced immune response against the 2009 pandemic H1N1 in study participants who had received vaccination against the swine flu in 1976.{{cite journal | vauthors = McCullers JA, Van De Velde LA, Allison KJ, Branum KC, Webby RJ, Flynn PM | title = Recipients of vaccine against the 1976 "swine flu" have enhanced neutralization responses to the 2009 novel H1N1 influenza virus | journal = Clinical Infectious Diseases | volume = 50 | issue = 11 | pages = 1487–92 | date = June 2010 | pmid = 20415539 | pmc = 2946351 | doi = 10.1086/652441 }} The 2009 H1N1 "swine flu" outbreak resulted in the rapid approval of pandemic influenza vaccines.{{Cite journal | vauthors = Doshi P |date=September 20, 2018 |title=Pandemrix vaccine: why was the public not told of early warning signs? |journal=BMJ |volume=362 |pages=k3948 |doi=10.1136/bmj.k3948 |issn=0959-8138 |pmid=|s2cid=52308748 }} Pandemrix was quickly modified to target the circulating strain and by late 2010, 70 million people had received a dose.{{cite journal | vauthors = Doshi P | title = Pandemrix vaccine: why was the public not told of early warning signs? | journal = BMJ | volume = 362 | pages = Infographic | date = September 20, 2018 | doi = 10.1136/bmj.k3948 | s2cid = 52308748 }} Eight years later, the BMJ gained access to early vaccine pharmacovigilance reports compiled by GSK (GlaxoSmithKline) during the pandemic, which the BMJ reported indicated death was 5.39 fold more likely with Pandemrix vs the other pandemic vaccines. However, more thorough and robust later analyses did not establish any increase of fatalities or most other serious adverse effects, with a possible rare exception for narcolepsy.{{cite journal | vauthors = Cohet C, van der Most R, Bauchau V, Bekkat-Berkani R, Doherty TM, Schuind A, Tavares Da Silva F, Rappuoli R, Garçon N, Innis BL | title = Safety of AS03-adjuvanted influenza vaccines: A review of the evidence | journal = Vaccine | volume = 37 | issue = 23 | pages = 3006–3021 | date = May 2019 | pmid = 31031030 | doi = 10.1016/j.vaccine.2019.04.048 | doi-access = free }}

File:Flu vaccination USS Gerald R. Ford.jpg in 2019]]

A quadrivalent flu vaccine administered by nasal mist was approved by the FDA in March 2012.{{cite web|url=http://www.medicalnewstoday.com/articles/242385.php|title=First Quadrivalent Vaccine Against Seasonal Flu Wins FDA Approval|date=March 2, 2012|url-status=live|archive-url=https://web.archive.org/web/20120304163117/http://www.medicalnewstoday.com/articles/242385.php|archive-date=March 4, 2012}}{{cite press release|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm294057.htm|title=FDA approves first quadrivalent vaccine to prevent seasonal influenza|publisher=U.S. Food and Drug Administration (FDA)|archive-url=https://web.archive.org/web/20121221123250/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm294057.htm|archive-date=December 21, 2012}} {{PD-notice}} Fluarix Quadrivalent was approved by the FDA in December 2012.{{cite web|url=https://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm332484.htm|title=December 14, 2012 Approval Letter – Fluarix Quadrivalent|publisher=U.S. Food and Drug Administration (FDA)|archive-url=https://web.archive.org/web/20130102191627/https://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm332484.htm|archive-date=January 2, 2013}} {{PD-notice}}

In 2014, the Canadian National Advisory Committee on Immunization (NACI) published a review of quadrivalent influenza vaccines.{{cite book | url=http://publications.gc.ca/collections/collection_2014/aspc-phac/HP40-117-2014-eng.pdf | title=Literature review on quadrivalent influenza vaccines | author = National Advisory Committee on Immunization (NACI) | date=July 2014 | publisher = Public Health Agency of Canada | id=Cat.: HP40-117/2014E-PDF Pub.: 140118 | isbn=978-1-100-24682-6 | access-date=January 11, 2020 | location=Ottawa | archive-date=August 1, 2020 | archive-url=https://web.archive.org/web/20200801233131/http://publications.gc.ca/collections/collection_2014/aspc-phac/HP40-117-2014-eng.pdf | url-status=live }}

Starting with the 2018–2019 influenza season most of the regular-dose egg-based flu shots and all the recombinant and cell-grown flu vaccines in the United States are quadrivalent.{{cite web | title=What You Should Know for the 2018-2019 Influenza Season | website=Centers for Disease Control and Prevention (CDC) | date=January 10, 2019 | url=https://www.cdc.gov/flu/about/season/flu-season-2018-2019.htm | access-date=February 5, 2020 | archive-date=August 6, 2020 | archive-url=https://web.archive.org/web/20200806183316/https://www.cdc.gov/flu/about/season/flu-season-2018-2019.htm | url-status=live }} {{PD-notice}} In the 2019–2020 influenza season all regular-dose flu shots and all recombinant influenza vaccine in the United States are quadrivalent.

In November 2019, the FDA approved Fluzone High-Dose Quadrivalent for use in the United States starting with the 2020–2021 influenza season.{{cite web | title=Fluzone High-Dose Quadrivalent | publisher=U.S. Food and Drug Administration (FDA) | date=November 4, 2019 | url=http://www.fda.gov/vaccines-blood-biologics/vaccines/fluzone-high-dose-quadrivalent | access-date=February 5, 2020 | id=STN: BL 103914 | archive-date=January 12, 2020 | archive-url=https://web.archive.org/web/20200112032546/https://www.fda.gov/vaccines-blood-biologics/vaccines/fluzone-high-dose-quadrivalent | url-status=live }} {{PD-notice}}{{cite press release | title=FDA approves Fluzone High-Dose Quadrivalent (Influenza Vaccine) for adults 65 years of age and older | website=Sanofi | date=November 4, 2019 | url=http://www.news.sanofi.us/2019-11-04-FDA-approves-Fluzone-R-High-Dose-Quadrivalent-Influenza-Vaccine-for-adults-65-years-of-age-and-older | access-date=February 5, 2020 | archive-date=August 1, 2020 | archive-url=https://web.archive.org/web/20200801215513/http://www.news.sanofi.us/2019-11-04-FDA-approves-Fluzone-R-High-Dose-Quadrivalent-Influenza-Vaccine-for-adults-65-years-of-age-and-older | url-status=live }}

In February 2020, the FDA approved Fluad Quadrivalent for use in the United States.{{cite press release | title=Seqirus Receives FDA Approval for Fluad Quadrivalent for Adults 65 Years and Older | website=Seqirus | date=February 24, 2020 | url=https://www.seqirus.us/news/seqirus-receives-fda-approval-for-fluad-quadrivalent-for-adults-65-years-and-older | access-date=August 25, 2020 | archive-date=August 26, 2020 | archive-url=https://web.archive.org/web/20200826060136/https://www.seqirus.us/news/seqirus-receives-fda-approval-for-fluad-quadrivalent-for-adults-65-years-and-older | url-status=live }} In July 2020, the FDA approved both Fluad and Fluad Quadrivalent for use in the United States for the 2020–2021 influenza season.{{cite press release | title=Seqirus Begins Shipping 2020/21 Influenza Vaccines to U.S. Market | website=Seqirus | date=July 30, 2020 | url=https://www.seqirus.us/news/seqirus-ships-2020-2021-influenza-vaccines-to-us-market | access-date=August 25, 2020 | archive-date=August 26, 2020 | archive-url=https://web.archive.org/web/20200826060135/https://www.seqirus.us/news/seqirus-ships-2020-2021-influenza-vaccines-to-us-market | url-status=live }}

The B/Yamagata lineage of influenza B, one of the four lineages targeted by quadrivalent vaccines, might have become extinct in 2020/2021 due to COVID-19 pandemic measures,{{cite journal | vauthors = Koutsakos M, Wheatley AK, Laurie K, Kent SJ, Rockman S | title = Influenza lineage extinction during the COVID-19 pandemic? | journal = Nature Reviews. Microbiology | volume = 19 | issue = 12 | pages = 741–742 | date = December 2021 | pmid = 34584246 | pmc = 8477979 | doi = 10.1038/s41579-021-00642-4 }} and there have been no naturally occurring cases confirmed since March 2020. In 2023, the World Health Organization concluded that protection against the Yamagata lineage was no longer necessary in the seasonal flu vaccine, so future vaccines are recommended to be trivalent instead of quadrivalent.{{cite web | title=Questions and Answers: Recommended composition of influenza virus vaccines for use in the southern hemisphere 2024 influenza season and development of candidate vaccine viruses for pandemic preparedness | author=World Health Organization | url=https://cdn.who.int/media/docs/default-source/influenza/who-influenza-recommendations/vcm-southern-hemisphere-recommendation-2024/202309_qanda_recommendation.pdf?sfvrsn=7a6906d1_5 | date=September 29, 2023 | access-date=October 26, 2023 | archive-date=October 10, 2023 | archive-url=https://web.archive.org/web/20231010045859/https://cdn.who.int/media/docs/default-source/influenza/who-influenza-recommendations/vcm-southern-hemisphere-recommendation-2024/202309_qanda_recommendation.pdf?sfvrsn=7a6906d1_5 | url-status=live }}{{cite web | title=WHO advisers recommend switch back to trivalent flu vaccines | vauthors = Schnirring L | website=CIDRAP | date=September 29, 2023 | url=https://www.cidrap.umn.edu/influenza-vaccines/who-advisers-recommend-switch-back-trivalent-flu-vaccines | access-date=October 26, 2023 | archive-date=December 18, 2023 | archive-url=https://web.archive.org/web/20231218231207/https://www.cidrap.umn.edu/influenza-vaccines/who-advisers-recommend-switch-back-trivalent-flu-vaccines | url-status=live }} For the 2024–2025 Northern Hemisphere influenza season, the FDA recommends removing B/Yamagata from all influenza vaccines.

The influenza vaccine is indicated for active immunization for the prevention of influenza disease caused by influenza virus subtypes A and type B contained in the vaccine.{{cite web | title=Flucelvax (influenza a virus a/georgia/12/2022 cvr-167 (h1n1) antigen (mdck cell derived, propiolactone inactivated), influenza a virus a/sydney/1304/2022 (h3n2) antigen (mdck cell derived, propiolactone inactivated), influenza b virus b/singapore/wuh4618/2021 antigen- mdck cell derived, propiolactone inactivated injection, suspension; Flucelvax (influenza a virus a/georgia/12/2022 crv-167 (h1n1) antigen (mdck cell derived, propiolactone inactivated), influenza a virus a/sydney/1304/2022 (h3n2) antigen (mdck cell derived, propiolactone inactivated), influenza b virus b/singapore/wuh4618/2021 antigen- mdck cell derived, propiolactone inactivated injection, suspension | website=DailyMed | date=July 1, 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3513dfb0-4d62-4ad1-bb15-75c7555896ff | access-date=August 31, 2024}}{{cite web | title=Fluad (influenza a virus a/victoria/4897/2022 ivr-238 (h1n1) antigen (formaldehyde inactivated), influenza a virus a/thailand/8/2022 ivr-237 (h3n2) antigen (formaldehyde inactivated), influenza b virus b/austria/1359417/2021 bvr-26 antigen- formaldehyde inactivated injection, suspension | website=DailyMed | date=July 1, 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9dbbf304-7be3-4417-8285-a8f5fd20f977 | access-date=August 31, 2024}}{{cite web | title=Fluzone High-Dose Quadrivalent Northern Hemisphere (influenza a virus a/victoria/4897/2022 ivr-238 (h1n1) antigen (formaldehyde inactivated), influenza a virus a/california/122/2022 san-022 (h3n2) antigen (formaldehyde inactivated), influenza b virus b/phuket/3073/2013 antigen (formaldehyde inactivated), and influenza b virus b/michigan/01/2021 antigen- formaldehyde inactivated injection, suspension | website=DailyMed | date=July 30, 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=03f2c9fc-534b-49ec-9113-81938b1eadb9 | access-date=August 31, 2024}}

The US Centers for Disease Control and Prevention (CDC) recommends the flu vaccine as the best way to protect people against the flu and prevent its spread. The flu vaccine can also reduce the severity of the flu if a person contracts a strain that the vaccine did not contain.{{cite web|title=Key Facts About Seasonal Flu Vaccine|url=https://www.cdc.gov/flu/prevent/keyfacts.htm|access-date=December 2, 2019|publisher=U.S. Centers for Disease Control and Prevention (CDC)|archive-url=https://web.archive.org/web/20191202203516/https://www.cdc.gov/flu/prevent/keyfacts.htm|archive-date=December 2, 2019|url-status=live|date=December 2, 2019}} {{PD-notice}} It takes about two weeks following vaccination for protective antibodies to form.

A 2012 meta-analysis found that flu vaccination was effective 67{{spaces}}percent of the time; the populations that benefited the most were HIV-positive adults aged 18 to 55 (76{{spaces}}percent), healthy adults aged 18 to 46 (approximately 70{{spaces}}percent), and healthy children aged six months to 24 months (66{{spaces}}percent).{{cite journal | vauthors = Osterholm MT, Kelley NS, Sommer A, Belongia EA | title = Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis | journal = The Lancet. Infectious Diseases | volume = 12 | issue = 1 | pages = 36–44 | date = January 2012 | pmid = 22032844 | doi = 10.1016/s1473-3099(11)70295-x }} The influenza vaccine also appears to protect against myocardial infarction with a benefit of 15–45%.{{cite journal | vauthors = MacIntyre CR, Mahimbo A, Moa AM, Barnes M | title = Influenza vaccine as a coronary intervention for prevention of myocardial infarction | journal = Heart | volume = 102 | issue = 24 | pages = 1953–1956 | date = December 2016 | pmid = 27686519 | pmc = 5256393 | doi = 10.1136/heartjnl-2016-309983 }}

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|x=1998-01-28, 1999-02-10, 1999-12-22, 2001-01-24, 2002-02-20, 2003-02-05, 2003-11-26, 2005-02-02, 2006-03-08, 2007-02-07, 2008-02-13, 2009-02-04, 2009-10-14, 2011-02-02, 2012-03-14, 2012-12-26, 2013-12-25, 2014-12-24, 2016-03-09, 2017-02-15, 2018-01-24, 2019-02-20, 2020-02-05, 2020-12-16, 2022-04-13

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|caption=US vaccine effectiveness (%) against symptomatic disease.{{cite web | title=Past Seasons Vaccine Effectiveness Estimates | website=U.S. Centers for Disease Control and Prevention (CDC) | date=January 29, 2020 | url=https://www.cdc.gov/flu/vaccines-work/past-seasons-estimates.html | archive-url=https://web.archive.org/web/20200212115345/https://www.cdc.gov/flu/vaccines-work/past-seasons-estimates.html | archive-date=February 12, 2020 | url-status=live | access-date=March 4, 2019}} {{PD-notice}}{{Cite journal |publisher=Centers for Disease Control and Prevention |date=August 13, 2004 |title=Assessment of the effectiveness of the 2003-04 influenza vaccine among children and adults--Colorado, 2003 |url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5331a1.htm |journal=MMWR. Morbidity and Mortality Weekly Report |volume=53 |issue=31 |pages=707–710 |issn=1545-861X |pmid=15306754 |author1=Centers for Disease Control Prevention (CDC) |access-date=April 27, 2022 |archive-date=April 27, 2022 |archive-url=https://web.archive.org/web/20220427184713/https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5331a1.htm |url-status=live }} At table.{{Cite journal |publisher=Centers for Disease Control and Prevention |date=January 16, 2004 |title=Preliminary assessment of the effectiveness of the 2003-04 inactivated influenza vaccine--Colorado, December 2003 |url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5301a3.htm |journal=MMWR. Morbidity and Mortality Weekly Report |volume=53 |issue=1 |pages=8–11 |issn=1545-861X |pmid=14724559 |author1=Centers for Disease Control Prevention (CDC) |access-date=April 25, 2022 |archive-date=May 29, 2022 |archive-url=https://web.archive.org/web/20220529044407/https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5301a3.htm |url-status=live }}{{cite web |title=Past Weekly Surveillance Reports |url=https://www.cdc.gov/flu/weekly/pastreports.htm |website=Centers for Disease Control and Prevention |date=April 29, 2022 |access-date=April 25, 2022 |archive-date=April 22, 2022 |archive-url=https://web.archive.org/web/20220422191530/https://www.cdc.gov/flu/weekly/pastreports.htm |url-status=live }}{{Cite journal |vauthors=Chung JR |date=March 11, 2022 |title=Interim Estimates of 2021–22 Seasonal Influenza Vaccine Effectiveness — United States, February 2022 |url=https://www.cdc.gov/mmwr/volumes/71/wr/mm7110a1.htm |journal=MMWR. Morbidity and Mortality Weekly Report |volume=71 |issue=10 |pages=365–370 |doi=10.15585/mmwr.mm7110a1 |pmid=35271561 |pmc=8911998 |issn=0149-2195 |access-date=May 25, 2022 |archive-date=May 16, 2022 |archive-url=https://web.archive.org/web/20220516045141/https://www.cdc.gov/mmwr/volumes/71/wr/mm7110a1.htm |url-status=live }} Notes: inestimable for the 2020–2021 flu season,{{cite web|url=https://www.healio.com/news/infectious-disease/20210603/cdc-unable-to-estimate-flu-vaccine-effectiveness-after-historically-mild-season|title=CDC unable to estimate flu vaccine effectiveness after historically mild season| vauthors = Dreisbach EN |publisher=Healio|date=June 3, 2021|access-date=April 18, 2022|archive-url=https://web.archive.org/web/20211008092935/https://www.healio.com/news/infectious-disease/20210603/cdc-unable-to-estimate-flu-vaccine-effectiveness-after-historically-mild-season|archive-date=October 8, 2021|url-status=live}} data missing for seasons 1999–2000 to 2002–2003.

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}}

A vaccine is assessed by its efficacy – the extent to which it reduces the risk of disease under controlled conditions – and its effectiveness – the observed reduction in risk after the vaccine is put into use.{{cite journal | vauthors = Fedson DS | title = Measuring protection: efficacy versus effectiveness | journal = Developments in Biological Standardization | volume = 95 | pages = 195–201 | year = 1998 | pmid = 9855432 }} In the case of influenza, effectiveness is expected to be lower than the efficacy because it is measured using the rates of influenza-like illness, which is not always caused by influenza.{{cite journal |vauthors=Demicheli V, Jefferson T, Ferroni E, Rivetti A, Di Pietrantonj C |date=February 2018 |title=Vaccines for preventing influenza in healthy adults |journal=Cochrane Database of Systematic Reviews |volume=2020 |issue=2 |page=CD001269 |doi=10.1002/14651858.CD001269.pub6 |pmc=6491184 |pmid=29388196 |doi-access=free |title-link=doi}} Studies on the effectiveness of flu vaccines in the real world are difficult; vaccines may be imperfectly matched, virus prevalence varies widely between years, and influenza is often confused with other influenza-like illnesses.{{cite journal | vauthors = Jefferson T | title = Influenza vaccination: policy versus evidence | journal = BMJ | volume = 333 | issue = 7574 | pages = 912–15 | date = October 2006 | pmid = 17068038 | pmc = 1626345 | doi = 10.1136/bmj.38995.531701.80 }} However, in most years (16 of the 19 years before 2007), the flu vaccine strains have been a good match for the circulating strains,{{cite web |url=https://www.cdc.gov/flu/pastseasons/0708season.htm |publisher=U.S. Centers for Disease Control and Prevention (CDC) |title=2007–2008 Influenza (Flu) Season |date=June 26, 2008 |url-status=live |archive-url=https://web.archive.org/web/20080306061959/http://www.cdc.gov/flu/about/qa/season.htm |archive-date=March 6, 2008 }} {{PD-notice}} and even a mismatched vaccine can often provide cross-protection. The virus rapidly changes due to antigenic drift, a slight mutation in the virus that causes a new strain to arise.{{cite journal | vauthors = Carrat F, Flahault A | title = Influenza vaccine: the challenge of antigenic drift | journal = Vaccine | volume = 25 | issue = 39–40 | pages = 6852–6862 | date = September 2007 | pmid = 17719149 | doi = 10.1016/j.vaccine.2007.07.027 }}

The effectiveness of seasonal flu vaccines varies significantly, with an estimated average efficacy of 50–60% against symptomatic disease,{{cite journal |vauthors=Sautto GA, Kirchenbaum GA, Ross TM |date=January 19, 2018 |title=Towards a universal influenza vaccine: different approaches for one goal |journal=Virology Journal |volume=15 |issue=1 |pages=17 |doi=10.1186/s12985-017-0918-y |pmc=5785881 |pmid=29370862 |doi-access=free }} depending on vaccine strain, age, prior immunity, and immune function, so vaccinated people can still contract influenza.{{cite journal |vauthors=Chow EJ, Doyle JD, Uyeki TM |date=June 12, 2019 |title=Influenza virus-related critical illness: prevention, diagnosis, treatment |journal=Critical Care |volume=23 |issue=1 |pages=214 |doi=10.1186/s13054-019-2491-9 |pmc=6563376 |pmid=31189475 |doi-access=free }} The effectiveness of flu vaccines is considered to be suboptimal, particularly among the elderly,{{cite journal |vauthors=Krammer F, Smith GJ, Fouchier RA, Peiris M, Kedzierska K, Doherty PC, Palese P, Shaw ML, Treanor J, Webster RG, García-Sastre A |date=June 28, 2018 |title=Influenza |journal=Nature Reviews Disease Primers |volume=4 |issue=1 |pages=3 |doi=10.1038/s41572-018-0002-y |pmc=7097467 |pmid=29955068}} but vaccination is still beneficial in reducing the mortality rate and hospitalization rate due to influenza as well as duration of hospitalization.{{cite journal |vauthors=Dabestani NM, Leidner AJ, Seiber EE, Kim H, Graitcer SB, Foppa IM, Bridges CB |date=September 2019 |title=A review of the cost-effectiveness of adult influenza vaccination and other preventive services |journal=Preventive Medicine |volume=126 |pages=105734 |doi=10.1016/j.ypmed.2019.05.022 |pmc=6778688 |pmid=31152830}} Vaccination of school-age children has shown to provide indirect protection for other age groups. LAIVs are recommended for children based on superior efficacy, especially for children under 6, and greater immunity against non-vaccine strains when compared to inactivated vaccines.{{cite journal |vauthors=Ghebrehewet S, MacPherson P, Ho A |date=December 7, 2016 |title=Influenza |journal=The BMJ |volume=355 |pages=i6258 |doi=10.1136/bmj.i6258 |pmc=5141587 |pmid=27927672}}{{cite journal |vauthors=Principi N, Esposito S |date=March 4, 2018 |title=Protection of children against influenza: Emerging problems |journal=Human Vaccines & Immunotherapeutics |volume=14 |issue=3 |pages=750–757 |doi=10.1080/21645515.2017.1279772 |pmc=5861800 |pmid=28129049}}

From 2012 to 2015 in New Zealand, vaccine effectiveness against admission to an intensive care unit was 82%.{{Cite journal |vauthors=Thompson MG, Pierse N, Huang QS, Prasad N, Duque J, Newbern EC, Baker MG, Turner N, McArthur C |date=September 18, 2018 |title=Influenza vaccine effectiveness in preventing influenza-associated intensive care admissions and attenuating severe disease among adults in New Zealand 2012–2015 |url=https://www.sciencedirect.com/science/article/pii/S0264410X18309976 |journal=Vaccine |volume=36 |issue=39 |pages=5916–5925 |doi=10.1016/j.vaccine.2018.07.028 |pmid=30077480 |s2cid=51922011 |issn=0264-410X |access-date=April 23, 2022 |archive-date=May 27, 2022 |archive-url=https://web.archive.org/web/20220527070911/https://www.sciencedirect.com/science/article/pii/S0264410X18309976 |url-status=live }} Effectiveness against hospitalized influenza illness in the 2019–2020 United States flu season was 41% overall and 54% in people aged 65 years or older.{{cite journal |vauthors=Tenforde MW, Talbot HK, Trabue CH, Gaglani M, McNeal TS, Monto AS, Martin ET, Zimmerman RK, Silveira FP, Middleton DB, Olson SM |title=Influenza Vaccine Effectiveness Against Hospitalization in the United States, 2019–2020 |journal=The Journal of Infectious Diseases |date=December 30, 2020 |volume=224 |issue=5 |pages=813–820 |doi=10.1093/infdis/jiaa800 |pmid=33378531 |pmc=8408767 |url=https://academic.oup.com/jid/article/224/5/813/6055595 |issn=0022-1899 |access-date=April 23, 2022 |archive-date=April 23, 2022 |archive-url=https://web.archive.org/web/20220423225806/https://academic.oup.com/jid/article/224/5/813/6055595 |url-status=live }} One review found 31% effectiveness against death among adults.{{Cite journal |vauthors=Ferdinands JM, Thompson MG, Blanton L, Spencer S, Grant L, Fry AM |date=June 23, 2021 |title=Does influenza vaccination attenuate the severity of breakthrough infections? A narrative review and recommendations for further research |url=https://www.sciencedirect.com/science/article/pii/S0264410X21005624 |journal=Vaccine |volume=39 |issue=28 |pages=3678–3695 |doi=10.1016/j.vaccine.2021.05.011 |pmid=34090700 |s2cid=235361401 |issn=0264-410X |access-date=April 23, 2022 |archive-date=April 23, 2022 |archive-url=https://web.archive.org/web/20220423225806/https://www.sciencedirect.com/science/article/pii/S0264410X21005624 |url-status=live }}

Repeated annual influenza vaccination generally offers consistent year-on-year protection against influenza. There is, however, suggestive evidence that repeated vaccinations may cause a reduction in vaccine effectiveness for certain influenza subtypes; this has no relevance to recommendations for yearly vaccinations but might influence future vaccination policy.{{cite journal |vauthors=Ramsay LC, Buchan SA, Stirling RG, Cowling BJ, Feng S, Kwong JC, Warshawsky BF |title=The impact of repeated vaccination on influenza vaccine effectiveness: a systematic review and meta-analysis |journal=BMC Med |volume=17 |issue=1 |page=9 |date=January 2019 |pmid=30626399 |pmc=6327561 |doi=10.1186/s12916-018-1239-8 |doi-access = free }}{{cite journal |vauthors=Belongia EA, Skowronski DM, McLean HQ, Chambers C, Sundaram ME, De Serres G |title=Repeated annual influenza vaccination and vaccine effectiveness: review of evidence |journal=Expert Rev Vaccines |volume=16 |issue=7 |pages=723–36 |date=July 2017 |pmid=28562111 |doi=10.1080/14760584.2017.1334554 | doi-access = free | title-link = doi }} {{As of|2019}}, the CDC recommends a yearly vaccine as most studies demonstrate overall effectiveness of annual influenza vaccination.{{cite web | title=Vaccine Effectiveness: How Well Do the Flu Vaccines Work? | website=U.S. Centers for Disease Control and Prevention (CDC) | date=October 12, 2018 | url=https://www.cdc.gov/flu/vaccines-work/vaccineeffect.htm | archive-url=https://web.archive.org/web/20191025023838/https://www.cdc.gov/flu/vaccines-work/vaccineeffect.htm | archive-date=October 25, 2019 | url-status=live | access-date=October 24, 2019}} {{PD-notice}}

There is not enough evidence to establish significant differences in the effectiveness of different influenza vaccine types,{{Cite journal |vauthors=Gemmill I, Young K |date=June 7, 2018 |title=Summary of the NACI literature review on the comparative effectiveness of subunit and split virus inactivated influenza vaccines in older adults |url=https://www.canada.ca/en/public-health/services/reports-publications/canada-communicable-disease-report-ccdr/monthly-issue/2018-44/issue-6-june-7-2018/article-2-summary-subunit-split-virus-influenza-vaccine.html |journal=Canada Communicable Disease Report |volume=44 |issue=6 |pages=129–133 |doi=10.14745/ccdr.v44i06a02 |issn=1481-8531 |pmc=6449119 |pmid=31015805 |access-date=June 2, 2020 |archive-date=May 17, 2020 |archive-url=https://web.archive.org/web/20200517233323/https://www.canada.ca/en/public-health/services/reports-publications/canada-communicable-disease-report-ccdr/monthly-issue/2018-44/issue-6-june-7-2018/article-2-summary-subunit-split-virus-influenza-vaccine.html |url-status=live }} but there are high-dose or adjuvanted products that induce a stronger immune response in the elderly.{{Cite web |date=August 26, 2021 |title=Flu & People 65 Years and Older |url=https://www.cdc.gov/flu/highrisk/65over.htm |access-date=April 21, 2022 |website=Centers for Disease Control and Prevention |archive-date=April 22, 2022 |archive-url=https://web.archive.org/web/20220422000747/https://www.cdc.gov/flu/highrisk/65over.htm |url-status=live }}

According to a 2016 study by faculty at the University of New South Wales, getting a flu shot was as effective or better at preventing a heart attack than even quitting smoking.{{cite journal | vauthors = MacIntyre CR, Mahimbo A, Moa AM, Barnes M | title = Influenza vaccine as a coronary intervention for prevention of myocardial infarction | journal = Heart | volume = 102 | issue = 24 | pages = 1953–1956 | date = December 2016 | pmid = 27686519 | doi = 10.1136/heartjnl-2016-309983 | pmc = 5256393 }}

A 2024 CDC study found that the 2024 flu vaccine reduced the risk of hospitalization from the flu by 35% in the Southern Hemisphere.{{Cite journal | vauthors = Zeno EE |date=2024 |title=Interim Effectiveness Estimates of 2024 Southern Hemisphere Influenza Vaccines in Preventing Influenza-Associated Hospitalization — REVELAC-i Network, Five South American Countries, March–July 2024 |url=https://www.cdc.gov/mmwr/volumes/73/wr/mm7339a1.htm?s_cid=mm7339a1_w |journal=MMWR. Morbidity and Mortality Weekly Report |language=en-us |volume=73 |issue=39 |pages=861–868 |doi=10.15585/mmwr.mm7339a1 |pmid=39361525 |issn=0149-2195|pmc=11449270 }} The research, conducted across five countries—Argentina, Brazil, Chile, Paraguay, and Uruguay—showed the vaccine was less effective than the one used in the previous season.{{Cite web | vauthors = Benadjaoud Y |title=Flu vaccine lowered risk of hospitalization in Southern Hemisphere by 35%: CDC |url=https://abcnews.go.com/Health/flu-vaccine-lowered-risk-hospitalization-southern-hemisphere-35/story?id=114470697 |access-date=2024-10-04 |website=ABC News |language=en}}

In April 2002, the US Advisory Committee on Immunization Practices (ACIP) encouraged that all children 6 to 23 months of age be vaccinated annually against influenza.{{Cite web|url = https://www.cdc.gov/flu/pandemic-resources/pandemic-timeline-1930-and-beyond.htm|title = Influenza Historic Timeline | Pandemic Influenza (Flu) | CDC|date = March 11, 2020|access-date = January 27, 2022|archive-date = January 30, 2022|archive-url = https://web.archive.org/web/20220130090654/https://www.cdc.gov/flu/pandemic-resources/pandemic-timeline-1930-and-beyond.htm|url-status = live}} In 2010, ACIP again recommended annual influenza vaccination for those 6 months of age and older. The CDC also recommends that everyone except infants under the age of six months should receive seasonal influenza vaccine.

Vaccination campaigns usually focus special attention on people who are at high risk of serious complications if they catch the flu, such as pregnant women, children under 5 years, the elderly, and people with chronic illnesses or weakened immune systems, as well as those to whom they are exposed, such as health care workers.{{cite web | title=Influenza (Seasonal) | website=World Health Organization (WHO) | date=November 6, 2018 | url=https://www.who.int/en/news-room/fact-sheets/detail/influenza-(seasonal) | archive-url=https://web.archive.org/web/20191025024946/https://www.who.int/en/news-room/fact-sheets/detail/influenza-(seasonal) | archive-date=October 25, 2019 | url-status=live | access-date=October 24, 2019}}

As the death rate is high among infants who catch influenza, the CDC and the WHO recommend that household contacts and caregivers of infants be vaccinated to reduce the risk of passing an influenza infection to the infant.{{cite web | title=Study of Flu-Related Deaths in Children Shows Healthy Children at Risk | website=U.S. Centers for Disease Control and Prevention (CDC) | date=February 12, 2018 | url=https://www.cdc.gov/flu/spotlights/2017-2018/flu-death-children.htm | archive-url=https://web.archive.org/web/20191202205242/https://www.cdc.gov/flu/spotlights/2017-2018/flu-death-children.htm | archive-date=December 2, 2019 | url-status=live | access-date=December 2, 2019 }} {{PD-notice}}

Also in healthy children, the vaccine appears to decrease the risk of influenza and possibly influenza-like illness.{{cite journal |vauthors=Jefferson T, Rivetti A, Di Pietrantonj C, Demicheli V |title=Vaccines for preventing influenza in healthy children |journal=Cochrane Database of Systematic Reviews |date=February 2018 |volume=2018 |page=CD004879 |doi=10.1002/14651858.CD004879.pub5 |pmid=29388195 |pmc=6491174 | doi-access = free | title-link = doi |issue=2 }} During the 2017–18 flu season, the CDC indicated that 85 percent of the children who died "likely will not have been vaccinated".{{cite news|title=U.S. CDC director urges flu vaccinations as pediatric deaths mount|url=https://www.reuters.com/article/us-usa-flu-cdc/u-s-cdc-director-urges-flu-vaccinations-as-pediatric-deaths-mount-idUSKBN1FB36O|publisher=Reuters|access-date=January 26, 2018|date=January 22, 2018|vauthors=Steenhuysen J|archive-date=May 6, 2021|archive-url=https://web.archive.org/web/20210506120529/https://www.reuters.com/article/us-usa-flu-cdc/u-s-cdc-director-urges-flu-vaccinations-as-pediatric-deaths-mount-idUSKBN1FB36O|url-status=live}}

In children under the age of two data were limited as of 2018.

In the United States, {{as of|January 2019|lc=yes}}, the CDC recommended that children aged six through 35 months may receive either 0.25{{spaces}}milliliters or 0.5{{spaces}}milliliters per dose of Fluzone Quadrivalent.{{cite web | title=Frequently Asked Influenza (Flu) Questions: 2019–2020 Season | website=U.S. Centers for Disease Control and Prevention (CDC) | date=November 5, 2019 | url=https://www.cdc.gov/flu/season/faq-flu-season-2019-2020.htm | archive-url=https://web.archive.org/web/20191201052345/https://www.cdc.gov/flu/season/faq-flu-season-2019-2020.htm | archive-date=December 1, 2019 | url-status=live | access-date=November 30, 2019}} {{PD-notice}}{{cite web | title=Fluzone High-Dose Quadrivalent | publisher=U.S. Food and Drug Administration (FDA) | date=November 14, 2019 | url=https://www.fda.gov/vaccines-blood-biologics/vaccines/fluzone-quadrivalent | archive-url=https://web.archive.org/web/20191201060617/https://www.fda.gov/vaccines-blood-biologics/vaccines/fluzone-high-dose-quadrivalent | archive-date=December 1, 2019 | url-status=live | access-date=November 30, 2019}} {{PD-notice}} There is no preference for one or the other dose volume of Fluzone Quadrivalent for that age group.

All persons 3 years of age and older should receive 0.5 milliliters per dose of Fluzone Quadrivalent. {{As of|October 2018}}, Afluria Quadrivalent is licensed for children six months of age and older in the United States.{{cite web | title=Afluria Quadrivalent | publisher=U.S. Food and Drug Administration (FDA) | date=November 8, 2019 | url=https://www.fda.gov/vaccines-blood-biologics/vaccines/afluria-quadrivalent | archive-url=https://web.archive.org/web/20191201060305/https://www.fda.gov/vaccines-blood-biologics/vaccines/afluria-quadrivalent | archive-date=December 1, 2019 | url-status=live | access-date=November 30, 2019}} {{PD-notice}} Children six months through 35 months of age should receive 0.25{{spaces}}milliliters for each dose of Afluria Quadrivalent. All persons 36 months of age and older should receive 0.5{{spaces}}milliliters per dose of Afluria Quadrivalent. For those not previously vaccinated or an unknown influenza vaccination history 2 doses are recommended, 4 weeks apart.

{{As of|February 2018}}, in Canada Afluria Tetra was only licensed for adults and children five years of age and older.{{cite web | title=Supplemental Statement – Afluria Tetra – An Advisory Committee Statement (ACS) |author=National Advisory Committee on Immunization (NACI) | website=Public Health Agency of Canada | date=November 2018 | url=https://www.canada.ca/en/public-health/services/publications/healthy-living/supplemental-statement-afluria-tetra.html | id=Cat.: HP37-25E-PDF Pub.: 180566 | access-date=January 11, 2020 | location=Ottawa | archive-date=January 12, 2020 | archive-url=https://web.archive.org/web/20200112032215/https://www.canada.ca/en/public-health/services/publications/healthy-living/supplemental-statement-afluria-tetra.html | url-status=live }}

In 2014, the Canadian National Advisory Committee on Immunization (NACI)had published a review of influenza vaccination in healthy 5–18-year-olds,{{cite report |url=http://publications.gc.ca/collections/collection_2014/aspc-phac/HP40-116-2014-eng.pdf |title=Literature review on influenza vaccination in healthy 5–18-year-olds |publisher=Public Health Agency of Canada |date=July 2014 |id=Cat.: HP40-116/2014E-PDF Pub.: 140116 |isbn=978-1-100-24681-9 |location=Ottawa |access-date=January 12, 2020 |archive-date=August 1, 2020 |archive-url=https://web.archive.org/web/20200801221759/http://publications.gc.ca/collections/collection_2014/aspc-phac/HP40-116-2014-eng.pdf |url-status=live }} and in 2015, published a review of the use of pediatric Fluad in children 6–72 months of age.{{cite report |url=https://www.canada.ca/content/dam/phac-aspc/migration/phac-aspc/naci-ccni/assets/pdf/pediatric-pediatrique-fluad-eng.pdf |title=Literature Review on Pediatric Fluad Influenza Vaccine Use in Children 6–72 Months of Age |year=2015 |publisher=Public Health Agency of Canada |access-date=January 11, 2020 |location=Ottawa |archive-date=May 17, 2020 |archive-url=https://web.archive.org/web/20200517230456/https://www.canada.ca/content/dam/phac-aspc/migration/phac-aspc/naci-ccni/assets/pdf/pediatric-pediatrique-fluad-eng.pdf |url-status=live }} In one study, conducted in a tertiary referral center, the rate of influenza vaccination in children was only 31%. Higher rates were found among immunosuppressed children (46%) and in children with inflammatory bowel disease (50%).{{cite journal | vauthors = Peleg N, Zevit N, Shamir R, Chodick G, Levy I | title = Seasonal influenza vaccination rates and reasons for non-vaccination in children with gastrointestinal disorders | journal = Vaccine | volume = 33 | issue = 1 | pages = 182–186 | date = January 2015 | pmid = 25444802 | doi = 10.1016/j.vaccine.2014.10.086 }}

File:Navy flu shot (50494239776).jpg administers a flu shot aboard the {{USS|Theodore Roosevelt|CVN-71}} in 2020.]]

In unvaccinated adults, 16% get symptoms similar to the flu, while about 10% of vaccinated adults do. Vaccination decreased confirmed cases of influenza from about 2.4% to 1.1%. No effect on hospitalization was found.

In working adults, a review by the Cochrane Collaboration found that vaccination resulted in a modest decrease in both influenza symptoms and working days lost, without affecting transmission or influenza-related complications. In healthy working adults, influenza vaccines can provide moderate protection against virologically confirmed influenza, though such protection is greatly reduced or absent in some seasons.{{cite journal |vauthors=Osterholm MT, Kelley NS, Sommer A, Belongia EA |date=January 2012 |title=Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis |journal=The Lancet. Infectious Diseases |volume=12 |issue=1 |pages=36–44 |doi=10.1016/S1473-3099(11)70295-X |pmid=22032844}}

In health care workers, a 2006 review found a net benefit.{{cite journal | vauthors = Burls A, Jordan R, Barton P, Olowokure B, Wake B, Albon E, Hawker J | title = Vaccinating healthcare workers against influenza to protect the vulnerable – is it a good use of healthcare resources? A systematic review of the evidence and an economic evaluation | journal = Vaccine | volume = 24 | issue = 19 | pages = 4212–21 | date = May 2006 | pmid = 16546308 | doi = 10.1016/j.vaccine.2005.12.043 }} Of the eighteen studies in this review, only two also assessed the relationship of patient mortality relative to staff influenza vaccine uptake; both found that higher rates of healthcare worker vaccination correlated with reduced patient deaths. A 2014 review found benefits to patients when health care workers were immunized, as supported by moderate evidence{{cite journal | vauthors = Ahmed F, Lindley MC, Allred N, Weinbaum CM, Grohskopf L | title = Effect of influenza vaccination of healthcare personnel on morbidity and mortality among patients: systematic review and grading of evidence | journal = Clinical Infectious Diseases | volume = 58 | issue = 1 | pages = 50–57 | date = January 2014 | pmid = 24046301 | doi = 10.1093/cid/cit580 | doi-access = free | title-link = doi }} based in part on the observed reduction in all-cause deaths in patients whose health care workers were given immunization compared with comparison patients where the workers were not offered the vaccine.{{cite journal | vauthors = Griffin MR | title = Influenza vaccination of healthcare workers: making the grade for action | journal = Clinical Infectious Diseases | volume = 58 | issue = 1 | pages = 58–60 | date = January 2014 | pmid = 24046312 | doi = 10.1093/cid/cit590 | doi-access = free | title-link = doi }}

Evidence for an effect in adults over 65 is unclear.{{cite journal | vauthors = Simonsen L, Viboud C, Taylor RJ, Miller MA, Jackson L | title = Influenza vaccination and mortality benefits: new insights, new opportunities | journal = Vaccine | volume = 27 | issue = 45 | pages = 6300–04 | date = October 2009 | pmid = 19840664 | doi = 10.1016/j.vaccine.2009.07.008 }} Systematic reviews examining both randomized controlled and case–control studies found a lack of high-quality evidence.{{cite journal |vauthors=Demicheli V, Jefferson T, Di Pietrantonj C, Ferroni E, Thorning S, Thomas RE, Rivetti A |date=February 2018 |title=Vaccines for preventing influenza in the elderly |journal=Cochrane Database of Systematic Reviews |volume=2 |issue=11 |page=CD004876 |doi=10.1002/14651858.CD004876.pub4 |pmc=6491101 |pmid=29388197 |doi-access=free |title-link=doi}} Reviews of case-control studies found effects against laboratory-confirmed influenza, pneumonia, and death among the community-dwelling elderly.{{cite journal | vauthors = Darvishian M, Bijlsma MJ, Hak E, van den Heuvel ER | title = Effectiveness of seasonal influenza vaccine in community-dwelling elderly people: a meta-analysis of test-negative design case-control studies | journal = The Lancet. Infectious Diseases | volume = 14 | issue = 12 | pages = 1228–39 | date = December 2014 | pmid = 25455990 | doi = 10.1016/S1473-3099(14)70960-0 }}{{cite journal | vauthors = Nichol KL, Nordin JD, Nelson DB, Mullooly JP, Hak E | title = Effectiveness of influenza vaccine in the community-dwelling elderly | journal = The New England Journal of Medicine | volume = 357 | issue = 14 | pages = 1373–81 | date = October 2007 | pmid = 17914038 | doi = 10.1056/NEJMoa070844 | s2cid = 14850833 | doi-access = free }}

The group most vulnerable to non-pandemic flu, the elderly, benefits least from the vaccine. There are multiple reasons behind this steep decline in vaccine efficacy, the most common of which are the declining immunological function and frailty associated with advanced age.{{cite journal | vauthors = Simonsen L, Taylor RJ, Viboud C, Miller MA, Jackson LA | title = Mortality benefits of influenza vaccination in elderly people: an ongoing controversy | journal = The Lancet. Infectious Diseases | volume = 7 | issue = 10 | pages = 658–66 | date = October 2007 | pmid = 17897608 | doi = 10.1016/S1473-3099(07)70236-0 }} In a non-pandemic year, a person in the United States aged 50–64 is nearly ten times more likely to die an influenza-associated death than a younger person, and a person over 65 is more than ten times more likely to die an influenza-associated death than the 50–64 age group.{{cite journal | vauthors = Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ, Fukuda K | title = Mortality associated with influenza and respiratory syncytial virus in the United States | journal = JAMA | volume = 289 | issue = 2 | pages = 179–86 | date = January 2003 | pmid = 12517228 | doi = 10.1001/jama.289.2.179 | s2cid = 5018362 | doi-access = free }}

There is a high-dose flu vaccine specifically formulated to provide a stronger immune response.{{cite web |url=http://www.sciencebasedmedicine.org/index.php/high-dose-flu-vaccine-for-the-elderly/ |title=High Dose Flu Vaccine for the Elderly « Science-Based Medicine |date=October 19, 2010 |publisher=Sciencebasedmedicine.org |access-date=October 17, 2013 |url-status=live |archive-url=https://web.archive.org/web/20130508081643/http://www.sciencebasedmedicine.org/index.php/high-dose-flu-vaccine-for-the-elderly/ |archive-date=May 8, 2013 }} Available evidence indicates that vaccinating the elderly with the high-dose vaccine leads to a stronger immune response against influenza than the regular-dose vaccine.{{cite web |url=https://www.cdc.gov/flu/prevent/qa_fluzone.htm |title=Fluzone High-Dose Seasonal Influenza Vaccine |publisher=U.S. Centers for Disease Control and Prevention (CDC) |date=September 6, 2019 |archive-url=https://web.archive.org/web/20191202211420/https://www.cdc.gov/flu/prevent/qa_fluzone.htm | archive-date=December 2, 2019 | url-status=live | access-date=December 2, 2019}}{{cite journal | vauthors = DiazGranados CA, Dunning AJ, Kimmel M, Kirby D, Treanor J, Collins A, Pollak R, Christoff J, Earl J, Landolfi V, Martin E, Gurunathan S, Nathan R, Greenberg DP, Tornieporth NG, Decker MD, Talbot HK | title = Efficacy of high-dose versus standard-dose influenza vaccine in older adults | journal = The New England Journal of Medicine | volume = 371 | issue = 7 | pages = 635–45 | date = August 2014 | pmid = 25119609 | doi = 10.1056/NEJMoa1315727 | s2cid = 205096393 | doi-access = free }}{{cite journal | title = High Dose Influenza Vaccine for Adults: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines | journal = Rapid Response Report | date = January 8, 2019 | vauthors = Wells C, Grobelna A | issn = 1922-8147 | url = https://cadth.ca/sites/default/files/pdf/htis/2018/RC1059%20High%20Dose%20Flu%20Vaccine%20Final.pdf | publisher = Canadian Agency for Drugs and Technologies in Health (CADTH) | location = Ottawa | pmid = 31141324 | access-date = August 15, 2022 | archive-date = August 1, 2020 | archive-url = https://web.archive.org/web/20200801200034/https://cadth.ca/sites/default/files/pdf/htis/2018/RC1059%20High%20Dose%20Flu%20Vaccine%20Final.pdf | url-status = live }}

A flu vaccine containing an adjuvant was approved by the US Food and Drug Administration (FDA) in November 2015, for use by adults aged 65 years of age and older. The vaccine is marketed as Fluad in the US and was first available in the 2016–2017 flu season. The vaccine contains the MF59C.1 adjuvant{{cite journal | vauthors = Mascagni P, Vicenzi E, Kajaste-Rudnitski A, Pellicciotta G, Monti A, Cervi C, Vitalucci R, Toffoletto F | title = Assessment of efficacy and safety of pandemic A/H1N1/2009 influenza vaccine in a group of health care workers | journal = La Medicina del Lavoro | volume = 103 | issue = 3 | pages = 220–29 | year = 2012 | pmid = 22838300 }} which is an oil-in-water emulsion of squalene oil. It is the first adjuvanted seasonal flu vaccine marketed in the United States.{{cite press release |title=FDA approves first seasonal influenza vaccine containing an adjuvant |url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm474295.htm |date=November 24, 2015 |publisher=U.S. Food and Drug Administration (FDA) |access-date=August 20, 2017 |archive-url=https://web.archive.org/web/20170722061508/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm474295.htm |archive-date=July 22, 2017 }} {{PD-notice}}{{cite web | title=Fluad | publisher=U.S. Food and Drug Administration (FDA) | date=November 8, 2019 | url=https://www.fda.gov/vaccines-blood-biologics/vaccines/fluad | archive-url=https://web.archive.org/web/20191202210615/https://www.fda.gov/vaccines-blood-biologics/vaccines/fluad | archive-date=December 2, 2019 | url-status=live | access-date=December 2, 2019 | id=STN 125510}} {{PD-notice}} It is not clear if there is a significant benefit for the elderly to use a flu vaccine containing the MF59C.1 adjuvant.{{cite journal | title = Influenza vaccine with squalene adjuvant: new preparation. No better than available products | journal = Prescrire International | volume = 13 | issue = 74 | pages = 206–08 | date = December 2004 | pmid = 15599987 }}{{cite journal | vauthors = Camilloni B, Basileo M, Valente S, Nunzi E, Iorio AM | title = Immunogenicity of intramuscular MF59-adjuvanted and intradermal administered influenza enhanced vaccines in subjects aged over 60: A literature review | journal = Human Vaccines & Immunotherapeutics | volume = 11 | issue = 3 | pages = 553–63 | year = 2015 | pmid = 25714138 | pmc = 4514405 | doi = 10.1080/21645515.2015.1011562}}

• {{lay source |template=cite web |date=May 1, 2018 |title=Literature Review Update on the Efficacy and Effectiveness of High-Dose (Fluzone High-Dose) and MF59-Adjuvanted (Fluad) Trivalent Inactivated Influenza Vaccines in Adults 65 Years of Age and Older |website=Public Health Agency of Canada |url=https://www.canada.ca/en/public-health/services/publications/healthy-living/executive-summary-literature-review-update-efficacy-effectiveness-fluzone-high-dose-fluad-trivalent-inactivated-influenza-vaccines-adults-65-older.html }}{{cite journal | vauthors = Van Damme P, Arnou R, Kafeja F, Fiquet A, Richard P, Thomas S, Meghlaoui G, Samson SI, Ledesma E | title = Evaluation of non-inferiority of intradermal versus adjuvanted seasonal influenza vaccine using two serological techniques: a randomised comparative study | journal = BMC Infectious Diseases | volume = 10 | page = 134 | date = May 2010 | pmid = 20504306 | pmc = 2895601 | doi = 10.1186/1471-2334-10-134 | doi-access = free }} Per Advisory Committee on Immunization Practices guidelines, Fluad can be used as an alternative to other influenza vaccines approved for people 65 years and older.{{cite web | title=Flu Vaccine With Adjuvant | website=U.S. Centers for Disease Control and Prevention (CDC) | date=September 4, 2019 | url=https://www.cdc.gov/flu/prevent/adjuvant.htm | archive-url=https://web.archive.org/web/20191202210120/https://www.cdc.gov/flu/prevent/adjuvant.htm | archive-date=December 2, 2019 | url-status=live | access-date=December 2, 2019}} {{PD-notice}}

Vaccinating healthcare workers who work with elderly people is recommended in many countries, with the goal of reducing influenza outbreaks in this vulnerable population.{{cite journal | vauthors = Haverkate M, D'Ancona F, Giambi C, Johansen K, Lopalco PL, Cozza V, Appelgren E |collaboration=VENICE project gatekeepers contact points collective | title = Mandatory and recommended vaccination in the EU, Iceland, and Norway: results of the VENICE 2010 survey on the ways of implementing national vaccination programmes | journal = Euro Surveillance | volume = 17 | issue = 22 | date = May 2012 | pmid = 22687916 | doi = 10.2807/ese.17.22.20183-en | doi-access = free | title-link = doi }}{{cite journal | vauthors = Field RI | title = Mandatory vaccination of health care workers: whose rights should come first? | journal = P & T | volume = 34 | issue = 11 | pages = 615–18 | date = November 2009 | pmid = 20140133 | pmc = 2810172 }}{{cite journal | vauthors = Kassianos G | title = Willingness of European healthcare workers to undergo vaccination against seasonal influenza: current situation and suggestions for improvement | journal = Drugs in Context | volume = 4 | page = 212268 | year = 2015 | pmid = 25657810 | pmc = 4316812 | doi = 10.7573/dic.212268 }} While there is no conclusive evidence from randomized clinical trials that vaccinating health care workers helps protect elderly people from influenza, there is tentative evidence of benefit.{{cite journal | vauthors = Thomas RE, Jefferson T, Lasserson TJ | title = Influenza vaccination for healthcare workers who care for people aged 60 or older living in long-term care institutions | journal = The Cochrane Database of Systematic Reviews | issue = 6 | page = CD005187 | date = June 2016 | volume = 2016 | pmid = 27251461 | doi = 10.1002/14651858.CD005187.pub5 | pmc = 8504984 | doi-access = free | title-link = doi }}

Fluad Quad was approved for use in Australia in September 2019,{{cite web | title=Fluad Quad Australian prescription medicine decision summary | website=Therapeutic Goods Administration (TGA) | date=December 13, 2019 | url=https://www.tga.gov.au/apm-summary/fluad-quad | access-date=August 24, 2020 | archive-date=March 8, 2020 | archive-url=https://web.archive.org/web/20200308183218/https://www.tga.gov.au/apm-summary/fluad-quad | url-status=live }} Fluad Quadrivalent was approved for use in the United States in February 2020,{{cite web | title=Fluad Quadrivalent | publisher=U.S. Food and Drug Administration (FDA) | date=July 2, 2020 | url=https://www.fda.gov/vaccines-blood-biologics/fluad-quadrivalent | access-date=August 25, 2020 | id=STN: 125510 | archive-date=August 11, 2020 | archive-url=https://web.archive.org/web/20200811160311/https://www.fda.gov/vaccines-blood-biologics/fluad-quadrivalent | url-status=live }} {{PD-notice}} and Fluad Tetra was authorized for use in the European Union in May 2020.{{cite web | title=Fluad Tetra EPAR | website=European Medicines Agency (EMA) | date=March 24, 2020 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/fluad-tetra | access-date=May 29, 2020 | archive-date=August 1, 2020 | archive-url=https://web.archive.org/web/20200801205143/https://www.ema.europa.eu/en/medicines/human/EPAR/fluad-tetra | url-status=live }}{{cite web | title=Fluad Tetra Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1433.htm | access-date=March 3, 2023 | archive-date=March 5, 2023 | archive-url=https://web.archive.org/web/20230305070644/https://ec.europa.eu/health/documents/community-register/html/h1433.htm | url-status=live }}

As well as protecting mother and child from the effects of an influenza infection, the immunization of pregnant women tends to increase their chances of experiencing a successful full-term pregnancy.{{cite journal | vauthors = Fell DB, Sprague AE, Liu N, Yasseen AS, Wen SW, Smith G, Walker MC | title = H1N1 influenza vaccination during pregnancy and fetal and neonatal outcomes | journal = American Journal of Public Health | volume = 102 | issue = 6 | pages = e33–40 | date = June 2012 | pmid = 22515877 | pmc = 3483960 | doi = 10.2105/AJPH.2011.300606 | type = Submitted manuscript }}

The trivalent inactivated influenza vaccine is protective in pregnant women infected with HIV.{{cite journal | vauthors = Madhi SA, Cutland CL, Kuwanda L, Weinberg A, Hugo A, Jones S, Adrian PV, van Niekerk N, Treurnicht F, Ortiz JR, Venter M, Violari A, Neuzil KM, Simões EA, Klugman KP, Nunes MC | title = Influenza vaccination of pregnant women and protection of their infants | journal = The New England Journal of Medicine | volume = 371 | issue = 10 | pages = 918–31 | date = September 2014 | pmid = 25184864 | doi = 10.1056/NEJMoa1401480 | hdl = 2263/42412 | hdl-access=free }}

Common side effects of vaccination include local injection-site reactions and cold-like symptoms. Fever, malaise, and myalgia are less common. Flu vaccines are contraindicated for people who have experienced a severe allergic reaction in response to a flu vaccine or to any component of the vaccine. LAIVs are not given to children or adolescents with severe immunodeficiency or to those who are using salicylate treatments because of the risk of developing Reye syndrome. LAIVs are also not recommended for children under the age of 2, pregnant women, and adults with immunosuppression. Inactivated flu vaccines cannot cause influenza and are regarded as safe during pregnancy.

While side effects of the flu vaccine may occur, they are usually minor, including soreness, redness, swelling around the point of injection, headache, fever, nausea, or fatigue.{{cite web |title=Flu shot |url=https://www.cdc.gov/flu/prevent/flushot.htm |website=CDC |access-date=September 24, 2020 |date=2020 |archive-date=December 2, 2019 |archive-url=https://web.archive.org/web/20191202232426/https://www.cdc.gov/flu/prevent/flushot.htm |url-status=live }} Side effects of a nasal spray vaccine may include runny nose, wheezing, sore throat, cough, or vomiting.{{cite web |title=Misconceptions about flu vaccines |url=https://www.cdc.gov/flu/prevent/misconceptions.htm |website=CDC |access-date=September 24, 2020 |date=2020 |archive-date=August 10, 2020 |archive-url=https://web.archive.org/web/20200810162228/https://www.cdc.gov/flu/prevent/misconceptions.htm |url-status=live }}

In some people, a flu vaccine may cause serious side effects, including an allergic reaction, but this is rare. Furthermore, the common side effects and risks are mild and temporary when compared to the risks and severe health effects of the annual influenza epidemic.

Contrary to a common misconception, flu shots cannot cause people to get the flu.{{Cite news | vauthors = McNeil Jr DG |date=October 1, 2018 |title=Over 80,000 Americans Died of Flu Last Winter, Highest Toll in Years |url=https://www.nytimes.com/2018/10/01/health/flu-deaths-vaccine.html |url-status=live |archive-url=https://web.archive.org/web/20181001182236/https://www.nytimes.com/2018/10/01/health/flu-deaths-vaccine.html |archive-date=October 1, 2018 |access-date=June 24, 2024 |work=The New York Times}}{{Cite web |title=5 myths about the flu vaccine |url=https://www.who.int/news-room/spotlight/influenza-are-we-ready/5-myths-about-the-flu-vaccine |url-status=live |archive-url=https://web.archive.org/web/20240214132129/https://www.who.int/news-room/spotlight/influenza-are-we-ready/5-myths-about-the-flu-vaccine |archive-date=February 14, 2024 |access-date=June 24, 2024 |website=World Health Organization}}

Although Guillain–Barré syndrome had been feared as a complication of vaccination, the CDC states that most studies on modern influenza vaccines have seen no link with Guillain–Barré.{{cite journal | vauthors = Haber P, Sejvar J, Mikaeloff Y, DeStefano F | title = Vaccines and Guillain-Barré syndrome | journal = Drug Safety | volume = 32 | issue = 4 | pages = 309–23 | year = 2009 | pmid = 19388722 | doi = 10.2165/00002018-200932040-00005 | s2cid = 33670594 }}{{cite journal | title = Reorganized text | journal = JAMA Otolaryngology–Head & Neck Surgery | volume = 141 | issue = 5 | page = 428 | date = May 2015 | pmid = 25996397 | doi = 10.1001/jamaoto.2015.0540 | s2cid = 26612829 }} Infection with influenza virus itself increases both the risk of death (up to one in ten thousand) and the risk of developing Guillain–Barré syndrome to a far higher level than the highest level of suspected vaccine involvement (approximately ten times higher by 2009 estimates).{{cite journal | vauthors = Stowe J, Andrews N, Wise L, Miller E | title = Investigation of the temporal association of Guillain-Barre syndrome with influenza vaccine and influenza-like illness using the United Kingdom General Practice Research Database | journal = American Journal of Epidemiology | volume = 169 | issue = 3 | pages = 382–88 | date = February 2009 | pmid = 19033158 | doi = 10.1093/aje/kwn310 | doi-access = free | title-link = doi }}{{cite journal | vauthors = Sivadon-Tardy V, Orlikowski D, Porcher R, Sharshar T, Durand MC, Enouf V, Rozenberg F, Caudie C, Annane D, van der Werf S, Lebon P, Raphaël JC, Gaillard JL, Gault E | title = Guillain-Barré syndrome and influenza virus infection | journal = Clinical Infectious Diseases | volume = 48 | issue = 1 | pages = 48–56 | date = January 2009 | pmid = 19025491 | doi = 10.1086/594124 | doi-access = free | title-link = doi }}

Although one review gives an incidence of about one case of Guillain–Barré per million vaccinations,{{cite journal | vauthors = Vellozzi C, Burwen DR, Dobardzic A, Ball R, Walton K, Haber P | title = Safety of trivalent inactivated influenza vaccines in adults: background for pandemic influenza vaccine safety monitoring | journal = Vaccine | volume = 27 | issue = 15 | pages = 2114–20 | date = March 2009 | pmid = 19356614 | doi = 10.1016/j.vaccine.2009.01.125 | url = https://zenodo.org/record/1259425 | access-date = May 21, 2020 | archive-date = August 1, 2020 | archive-url = https://web.archive.org/web/20200801190854/https://zenodo.org/record/1259425 | url-status = live }} a large study in China, covering close to a hundred million doses of vaccine against the 2009 H1N1 "swine" flu found only eleven cases of Guillain–Barré syndrome, (0.1 per million doses) total incidence in persons vaccinated, actually lower than the normal rate of the disease in China, and no other notable side effects.{{cite news| title = Last Year's H1N1 Flu Vaccine Was Safe, Study Finds| date = February 2, 2011| url = http://health.usnews.com/health-news/managing-your-healthcare/research/articles/2011/02/02/last-years-h1n1-flu-vaccine-was-safe-study-finds| vauthors = Reinberg S | work = U.S. News & World Report| url-status = live| archive-url = https://web.archive.org/web/20130425164738/http://health.usnews.com/health-news/managing-your-healthcare/research/articles/2011/02/02/last-years-h1n1-flu-vaccine-was-safe-study-finds| archive-date = April 25, 2013 }}

File:Ampliação e Modernização da Fábrica de Vacina (40225018103).jpg]]

Although most influenza vaccines are produced using egg-based techniques, influenza vaccines are nonetheless still recommended as safe for people with egg allergies, even if severe, as no increased risk of allergic reaction to the egg-based vaccines has been shown for people with egg allergies.{{cite news |date=March 27, 2021 |title=Australia's first cell-based influenza vaccines to roll out this flu season |website=ABC News |url=https://www.abc.net.au/news/health/2021-03-27/flu-new-vaccine-cell-based-australian-first/100023908 |url-status=live |access-date=April 28, 2021 |archive-url=https://web.archive.org/web/20210427180254/https://www.abc.net.au/news/health/2021-03-27/flu-new-vaccine-cell-based-australian-first/100023908 |archive-date=April 27, 2021 |vauthors=Roberts L}} Studies examining the safety of influenza vaccines in people with severe egg allergies found that anaphylaxis was very rare, occurring in 1.3 cases per million doses given.

Monitoring for symptoms from vaccination is recommended in those with more severe symptoms.{{cite journal|author=National Advisory Committee on Immunization (NACI) |title=Statement on Seasonal Influenza Vaccine for 2012–2013|journal=Canada Communicable Disease Report|date=August 2012|volume=38|url=http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/12vol38/acs-dcc-2/assets/pdf/acs-dcc-2-eng.pdf|archive-url=https://web.archive.org/web/20130117234635/http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/12vol38/acs-dcc-2/assets/pdf/acs-dcc-2-eng.pdf|archive-date=January 17, 2013|access-date=July 18, 2013 | location=Ottawa }} A study of nearly 800 children with egg allergy, including over 250 with previous anaphylactic reactions, had zero systemic allergic reactions when given the live attenuated flu vaccine.{{cite journal | vauthors = Turner PJ, Southern J, Andrews NJ, Miller E, Erlewyn-Lajeunesse M | title = Safety of live attenuated influenza vaccine in young people with egg allergy: multicentre prospective cohort study | journal = BMJ | volume = 351 | page = h6291 | date = December 2015 | pmid = 26645895 | pmc = 4673102 | doi = 10.1136/bmj.h6291 }}{{cite journal | vauthors = Greenhawt M | title = Live attenuated influenza vaccine for children with egg allergy | journal = BMJ | volume = 351 | page = h6656 | date = December 2015 | pmid = 26657778 | doi = 10.1136/bmj.h6656 | s2cid = 37037904 }}

Vaccines produced using other technologies, notably recombinant vaccines and those based on cell culture rather than egg protein, started to become available in 2012 in the US, and later in Europe and Australia.

Several studies have identified an increased incidence of narcolepsy among recipients of the pandemic H1N1 influenza AS03-adjuvanted vaccine;{{cite book|title=Technical Report: Narcolepsy in association with pandemic influenza vaccination|year=2012|publisher=European Centre for Disease Prevention and Control (ECDC)|location=Stockholm, Sweden|isbn=978-92-9193-388-4|url=http://www.ecdc.europa.eu/en/publications/Publications/Vaesco%20report%20FINAL%20with%20cover.pdf|archive-url=https://web.archive.org/web/20131231001407/http://www.ecdc.europa.eu/en/publications/Publications/Vaesco%20report%20FINAL%20with%20cover.pdf|archive-date=December 31, 2013|access-date=December 30, 2013}} efforts to identify a mechanism for this suggest that narcolepsy is autoimmune, and that the AS03-adjuvanted H1N1 vaccine may mimic hypocretin, serving as a trigger.{{cite journal |doi=10.1038/nature.2013.14413 |title=Narcolepsy confirmed as autoimmune disease |journal=Nature |year=2013 | vauthors = Yong E |s2cid=74850662 }}

Some injection-based flu vaccines intended for adults in the United States contain thiomersal (also known as thimerosal), a mercury-based preservative.{{cite web | title=Thimerosal in Flu Vaccine | website=U.S. Centers for Disease Control and Prevention | date=October 16, 2015 | url=https://www.cdc.gov/flu/prevent/thimerosal.htm | archive-url=https://web.archive.org/web/20191202222555/https://www.cdc.gov/flu/prevent/thimerosal.htm | archive-date=December 2, 2019 | url-status=live | access-date=December 2, 2019}} {{PD-notice}}{{cite web | title=Thimerosal in Vaccines Thimerosal – Concerns – Vaccine Safety | website=U.S. Centers for Disease Control and Prevention | date=October 27, 2015 | url=https://www.cdc.gov/vaccinesafety/concerns/thimerosal/index.html | archive-url=https://web.archive.org/web/20191102181824/https://www.cdc.gov/vaccinesafety/concerns/thimerosal/index.html | archive-date=November 2, 2019 | url-status=live | access-date=December 2, 2019}} {{PD-notice}} Despite some controversy in the media,{{cite journal | vauthors = Offit PA | title = Thimerosal and vaccines – a cautionary tale | journal = The New England Journal of Medicine | volume = 357 | issue = 13 | pages = 1278–79 | date = September 2007 | pmid = 17898096 | doi = 10.1056/NEJMp078187 | s2cid = 36318722 | doi-access = free }} the World Health Organization's Global Advisory Committee on Vaccine Safety has concluded that there is no evidence of toxicity from thiomersal in vaccines and no reason on grounds of safety to change to more-expensive single-dose administration.{{cite web |title= Thiomersal and vaccines |author= Global Advisory Committee on Vaccine Safety |publisher= World Health Organization (WHO) |url=https://www.who.int/vaccine_safety/topics/thiomersal/en/index.html |date= July 14, 2006 |access-date= November 20, 2007 |archive-url= https://web.archive.org/web/20091106092438/http://www.who.int/vaccine_safety/topics/thiomersal/en/index.html |archive-date= November 6, 2009 }}

Exercising before the influenza vaccine is not thought to be harmful but there is no evidence of a beneficial effect either.{{cite journal | vauthors = Grande AJ, Reid H, Thomas EE, Nunan D, Foster C | title = Exercise prior to influenza vaccination for limiting influenza incidence and its related complications in adults | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | issue = 8 | pages = CD011857 | date = August 2016 | pmid = 27545762 | pmc = 8504432 | doi = 10.1002/14651858.CD011857.pub2 }}

{{anchor|Trivalent}}

{{anchor|inactivated trivalent injection}}

{{Main|List of seasonal influenza vaccines}}

Seasonal flu vaccines are available either as:

• a trivalent or quadrivalent injection, which contains the inactivated form of the virus. This is usually an intramuscular injection, though subcutaneous and intradermal routes can also be protective.{{cite book| vauthors = Plotkin SA, Orenstein WA |title= Vaccines|year=1988|publisher=W.B. Saunders Company|location=Philadelphia|isbn=978-0-7216-1946-0|url-access=registration |url= https://archive.org/details/vaccines0000unse/page/424/mode/1up |page=424|access-date=September 7, 2020}}
• a nasal spray of live attenuated influenza vaccine, which contains the live but attenuated (weakened) form of the virus.

Injected vaccines induce protection based on an immune response to the antigens present on the inactivated virus, while the nasal spray works by establishing short-term infection in the nasal passages.{{citation|title=Product Monograph: Flumist|date=June 20, 2014|publisher=Astrazeneca Canada Inc.|url=https://www.astrazeneca.ca/content/dam/az-ca/downloads/productinformation/flumist-qlaiv-product-monograph-en.pdf|access-date=September 5, 2020|archive-date=September 30, 2020|archive-url=https://web.archive.org/web/20200930143924/https://www.astrazeneca.ca/content/dam/az-ca/downloads/productinformation/flumist-qlaiv-product-monograph-en.pdf|url-status=live}}

{{Further|Historical annual reformulations of the influenza vaccine}}

{{See also|2009 flu pandemic vaccine}}

Each year, three influenza strains are chosen for inclusion in the forthcoming year's seasonal flu vaccination by the Global Influenza Surveillance and Response System of the World Health Organization (WHO).{{cite web |title=Global Influenza Surveillance and Response System (GISRS) |url=https://www.who.int/influenza/gisrs_laboratory/en/ |archive-url=https://web.archive.org/web/20111003070329/http://www.who.int/influenza/gisrs_laboratory/en/ |archive-date=October 3, 2011 |publisher=World Health Organization |access-date=October 22, 2019}} The recommendation for trivalent vaccine comprises two strains of Influenza A (one each of A/H1N1 and A/H3N2), and one strain of influenza B (B/Victoria), together representing strains thought most likely to cause significant human suffering in the coming season. Starting in 2012, WHO has also recommended a second influenza B strain (B/Yamagata) for use in quadrivalent vaccines; this was discontinued in 2024.

:"The WHO Global Influenza Surveillance Network was established in 1952 (renamed "Global Influenza Surveillance and Response System" in 2011).{{cite web |title=Spotlight: Influenza |url=https://www.who.int/influenza/spotlight |publisher=World Health Organization |access-date=October 22, 2019 |archive-date=October 18, 2019 |archive-url=https://web.archive.org/web/20191018013229/https://www.who.int/influenza/spotlight |url-status=live }} The network comprises four WHO Collaborating Centres (WHO CCs) and 112 institutions in 83 countries, which are recognized by WHO as WHO National Influenza Centres (NICs). These NICs collect specimens in their country and perform primary virus isolation and preliminary antigenic characterization. They ship newly isolated strains to WHO CCs for high-level antigenic and genetic analysis, the result of which forms the basis for WHO recommendations on the composition of influenza vaccine for the Northern and Southern Hemisphere each year."{{cite web |url=https://www.who.int/csr/disease/influenza/influenzanetwork/en/index.html |work=WHO |title=Global influenza surveillance |archive-url=https://web.archive.org/web/20030430160359/http://www.who.int/csr/disease/influenza/influenzanetwork/en/index.html |archive-date=April 30, 2003 }}

Formal WHO recommendations were first issued in 1973. Beginning in 1999 there have been two recommendations per year: one for the northern hemisphere and the other for the southern hemisphere.{{cite book | title=WHO Report on Global Surveillance of Epidemic-prone Infectious Diseases – Influenza | publisher=World Health Organization (WHO) | year=2000 | id=WHO/CDS/CSR/ISR/2000/1 | hdl=10665/66485 | hdl-access=free | last1=Organization | first1=World Health }}

Due to the widespread use of non-pharmaceutical interventions at the beginning of the COVID-19 pandemic, the B/Yamagata influenza lineage has not been isolated since March 2020 and may have been eradicated. Starting with the 2024 Southern Hemisphere influenza season, the WHO and other regulatory bodies have removed B/Yamagata from influenza vaccine recommendations.{{cite web |last=Schnirring |first=Lisa |title=WHO advisers recommend switch back to trivalent flu vaccines |work=Center for Infectious Disease Research and Policy |url=https://www.cidrap.umn.edu/influenza-vaccines/who-advisers-recommend-switch-back-trivalent-flu-vaccines |date=September 29, 2023 |access-date=January 23, 2024 |archive-url=https://web.archive.org/web/20231218231207/https://www.cidrap.umn.edu/influenza-vaccines/who-advisers-recommend-switch-back-trivalent-flu-vaccines |archive-date=December 18, 2023 |url-status=live}}{{cite web | title=Use of Trivalent Influenza Vaccines for the 2024-2025 U.S. flu season | website=U.S. Food and Drug Administration (FDA) | date=March 5, 2024 | url=https://www.fda.gov/vaccines-blood-biologics/lot-release/use-trivalent-influenza-vaccines-2024-2025-us-influenza-season | access-date=March 7, 2024 | archive-date=March 7, 2024 | archive-url=https://web.archive.org/web/20240307043000/https://www.fda.gov/vaccines-blood-biologics/lot-release/use-trivalent-influenza-vaccines-2024-2025-us-influenza-season | url-status=live }} {{PD-notice}}{{cite web | title=EU recommendations for 2024/2025 seasonal flu vaccine composition | website=European Medicines Agency (EMA) | date=March 26, 2024 | url=https://www.ema.europa.eu/en/news/eu-recommendations-2024-2025-seasonal-flu-vaccine-composition | access-date=March 28, 2024 | archive-date=March 28, 2024 | archive-url=https://web.archive.org/web/20240328064245/https://www.ema.europa.eu/en/news/eu-recommendations-2024-2025-seasonal-flu-vaccine-composition | url-status=live }}

Various public health organizations, including the World Health Organization (WHO), recommend that yearly influenza vaccination be routinely offered, particularly to people at risk of complications of influenza and those individuals who live with or care for high-risk individuals, including:

• people aged 50 years of age or older
• people with chronic lung diseases, including asthma
• people with chronic heart diseases
• people with chronic liver diseases
• people with chronic kidney diseases
• people who have had their spleen removed or whose spleen is not working properly{{medical citation needed|date=August 2021}}
• people who are immunocompromised
• residents of nursing homes and other long-term care facilities
• health care workers (both to prevent sickness and to prevent spread to their patients){{cite journal | vauthors = To KW, Lai A, Lee KC, Koh D, Lee SS | title = Increasing the coverage of influenza vaccination in healthcare workers: review of challenges and solutions | journal = The Journal of Hospital Infection | volume = 94 | issue = 2 | pages = 133–42 | date = October 2016 | pmid = 27546456 | doi = 10.1016/j.jhin.2016.07.003 }}
• {{visible anchor|pregnant|text=women who are or will be pregnant during the influenza season}}
• children and adolescents (aged 6 months through 18 years) who are receiving aspirin- or salicylate-containing medications and who might be at risk for experiencing Reye syndrome after influenza virus infection
• American Indians/Alaska Natives
• people who are extremely obese (body mass index ≥40 for adults)

The flu vaccine is contraindicated for those under six months of age and those with severe, life-threatening allergies to flu vaccine or any ingredient in the vaccine.{{cite web | title=Seasonal Flu Shot | website=U.S. Centers for Disease Control and Prevention (CDC) | date=December 9, 2019 | url=https://www.cdc.gov/flu/prevent/flushot.htm | access-date=January 12, 2020 | archive-date=December 2, 2019 | archive-url=https://web.archive.org/web/20191202232426/https://www.cdc.gov/flu/prevent/flushot.htm | url-status=live }} {{PD-notice}}

{{as of|2016}}, the World Health Organization (WHO) recommends seasonal influenza vaccination for:{{cite web |url=https://www.who.int/influenza/vaccines/use/en/ |title=Vaccine use |publisher=World Health Organization (WHO) |access-date=January 15, 2017 |archive-url=https://web.archive.org/web/20121215120730/http://www.who.int/influenza/vaccines/use/en/ |archive-date=December 15, 2012 }}{{cite web |url=https://www.who.int/mediacentre/factsheets/fs211/en/ |title=Influenza (Seasonal) Fact sheet |publisher=World Health Organization (WHO) |date=November 2016 |access-date=January 15, 2017 |url-status=live |archive-url=https://web.archive.org/web/20141130051058/http://www.who.int/mediacentre/factsheets/fs211/en/ |archive-date=November 30, 2014 }}{{cite web | title=Influenza (Seasonal) | website=WHO | date=November 6, 2018 | url=https://www.who.int/en/news-room/fact-sheets/detail/influenza-(seasonal) | archive-url=https://web.archive.org/web/20191014062745/https://www.who.int/en/news-room/fact-sheets/detail/influenza-(seasonal) | archive-date=October 14, 2019 | url-status=live | access-date=October 14, 2019}}{{cite web | title=Methods for assessing influenza vaccination coverage in target groups (2016) | website=WHO/Europe | date=March 19, 2018 | url=http://www.euro.who.int/en/health-topics/communicable-diseases/influenza/publications/2016/methods-for-assessing-influenza-vaccination-coverage-in-target-groups-2016 | access-date=October 14, 2019 | archive-date=October 14, 2019 | archive-url=https://web.archive.org/web/20191014063302/http://www.euro.who.int/en/health-topics/communicable-diseases/influenza/publications/2016/methods-for-assessing-influenza-vaccination-coverage-in-target-groups-2016 | url-status=live }}{{cite web | title=Recommendations on influenza vaccination during the 2019–2020 winter season | website=WHO/Europe | date=September 24, 2019 | url=http://www.euro.who.int/en/health-topics/communicable-diseases/influenza/publications/2019/recommendations-on-influenza-vaccination-during-the-20192020-winter-season-2019 | access-date=October 14, 2019 | archive-date=October 14, 2019 | archive-url=https://web.archive.org/web/20191014063259/http://www.euro.who.int/en/health-topics/communicable-diseases/influenza/publications/2019/recommendations-on-influenza-vaccination-during-the-20192020-winter-season-2019 | url-status=live }}

First priority:

• Pregnant women

Second priority (in no particular order):

• Children aged 6–59 months
• Elderly
• Individuals with specific chronic medical conditions
• Health-care workers

The National Advisory Committee on Immunization (NACI), the group that advises the Public Health Agency of Canada, recommends that everyone over six months of age be encouraged to receive annual influenza vaccination and that children between the age of six months and 24 months, and their household contacts, should be considered a high priority for the flu vaccine.{{cite report |title=Canadian Immunization Guide Chapter on Influenza and Statement on Seasonal Influenza Vaccine for 2019–2020 |date=May 2019 |publisher=Public Health Agency of Canada |url=https://www.canada.ca/content/dam/phac-aspc/documents/services/publications/healthy-living/canadian-immunization-guide-statement-seasonal-influenza-vaccine-2019-2020/NACI_Stmt_on_Seasonal_Influenza_Vaccine_2019-2020_v12.3_EN.pdf |id=Cat.: HP37-25E-PDF; Pub.: 180883 |access-date=June 2, 2020 |archive-date=July 16, 2020 |archive-url=https://web.archive.org/web/20200716080446/https://www.canada.ca/content/dam/phac-aspc/documents/services/publications/healthy-living/canadian-immunization-guide-statement-seasonal-influenza-vaccine-2019-2020/NACI_Stmt_on_Seasonal_Influenza_Vaccine_2019-2020_v12.3_EN.pdf |url-status=live }}

Particularly:

• People at high risk of influenza-related complications or hospitalization, including people who are morbidly obese, healthy pregnant women, children aged 6–59 months, the elderly, aboriginals, and people with one of an itemized list of chronic health conditions
• People capable of transmitting influenza to those at high risk, including household contacts and healthcare workers
• People who provide essential community services
• Certain poultry workers

Live attenuated influenza vaccine (LAIV) was not available in Canada for the 2019–2020 season.

The European Centre for Disease Prevention and Control (ECDC) recommends vaccinating the elderly as a priority, with a secondary priority for people with chronic medical conditions and health care workers.{{cite web | title=Risk groups for severe influenza | website=European Centre for Disease Prevention and Control (ECDC) | date=October 20, 2017 | url=https://www.ecdc.europa.eu/en/seasonal-influenza/prevention-and-control/vaccines/risk-groups | archive-url=https://web.archive.org/web/20191022071926/https://www.ecdc.europa.eu/en/seasonal-influenza/prevention-and-control/vaccines/risk-groups | archive-date=October 22, 2019 | url-status=live | access-date=October 22, 2019}}

The influenza vaccination strategy is generally that of protecting vulnerable people, rather than limiting influenza circulation or eliminating human influenza sickness. This is in contrast with the high herd immunity strategies for other infectious diseases such as polio and measles.{{cite news|title=ECDC Reviews – New WHO recommendations on seasonal influenza ...|url=http://ecdc.europa.eu/en/activities/sciadvice/_layouts/forms/Review_DispForm.aspx?List=a3216f4c-f040-4f51-9f77-a96046dbfd72&ID=698|access-date=December 25, 2016|work=European Centre for Disease Prevention and Control (ECDC)|url-status=live|archive-url=https://web.archive.org/web/20170510115326/http://ecdc.europa.eu/en/activities/sciadvice/_layouts/forms/Review_DispForm.aspx?List=a3216f4c-f040-4f51-9f77-a96046dbfd72&ID=698|archive-date=May 10, 2017}} This is also due in part to the financial and logistics burden associated with the need of an annual injection.{{cite web |title= ECDC Guidance: Priority risk groups for influenza vaccination |pages= 7–8 |url= http://ecdc.europa.eu/en/publications/Publications/0808_GUI_Priority_Risk_Groups_for_Influenza_Vaccination.pdf |publisher= European Centre for Disease Prevention and Control (ECDC) |access-date= December 25, 2016 |archive-url= https://web.archive.org/web/20161225214347/http://ecdc.europa.eu/en/publications/Publications/0808_GUI_Priority_Risk_Groups_for_Influenza_Vaccination.pdf |archive-date= December 25, 2016 }}

The National Health Service in the United Kingdom provides flu vaccination to:

• people who are aged 65 or over
• people who have certain long-term health conditions
• people who are pregnant
• people who live in a care home
• people who are the main carer for an older or disabled person, or receive a carer's allowance
• people who live with someone who has a weakened immune system.{{cite web |title=Flu vaccine |url=https://www.nhs.uk/vaccinations/flu-vaccine/ |website=nhs.uk |language=en |date=6 March 2024}}

This vaccination is available free of charge to people in these groups. People outside these groups aged between 18 and 65 years of age can also receive private flu vaccination for a small fee from pharmacies and some private surgeries.{{cite web |title=Private Flu Vaccinations {{!}} Book a pharmacy appointment {{!}} Patient Access |url=https://www.patientaccess.com/services/flu/private-flu-vaccination |website=www.patientaccess.com |language=en}}

File:Flu_Shot_Advertising.jpg.]]

In the United States routine influenza vaccination is recommended for all persons aged six months and over.{{cite journal | vauthors = Grohskopf LA, Ferdinands JM, Blanton LH, Broder KR, Loehr J | title = Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices — United States, 2024–25 Influenza Season | journal = MMWR. Recommendations and Reports | volume=73 | issue=5 | date = August 2024 | pmid = 39197095 | doi = 10.15585/mmwr.rr7305a1 | doi-access = free | pages = 1–25 | pmc = 11501009 | url = https://www.cdc.gov/mmwr/volumes/73/rr/pdfs/rr7305a1-H.pdf }}{{cite journal |vauthors=Grohskopf LA, Alyanak E, Ferdinands JM, Broder KR, Blanton LH, Talbot HK, Fry AM |title=Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021-22 Influenza Season |journal=MMWR Recomm Rep |volume=70 |issue=5 |pages=1–28 |date=August 2021 |pmid=34448800 |doi=10.15585/mmwr.rr7005a1 |pmc=8407757 |doi-access=free |url= https://www.cdc.gov/mmwr/volumes/70/rr/pdfs/rr7005a1-H.pdf |access-date=August 29, 2021 |archive-date=August 27, 2021 |archive-url=https://web.archive.org/web/20210827010217/https://www.cdc.gov/mmwr/volumes/70/rr/pdfs/rr7005a1-H.pdf |url-status=live }} {{PD-notice}}{{cite web|url=https://www.cdc.gov/flu/highrisk/children.htm|title=Children & Influenza (Flu)|publisher=U.S. Centers for Disease Control and Prevention (CDC)|date=October 23, 2019|url-status=live|archive-url=https://web.archive.org/web/20191111042856/https://www.cdc.gov/flu/highrisk/children.htm|archive-date=November 11, 2019}} {{PD-notice}} It takes up to two weeks after vaccination for sufficient antibodies to develop in the body. The CDC recommends vaccination before the end of October, although it considers getting a vaccine in December or even later to be still beneficial. The U.S. military also requires a flu shot annually for its active and reserve servicemembers.{{Cite news |last=Rahman |first=Khaleda |date=October 21, 2021 |title=Full List of Vaccines Mandated by the U.S. Military |url=https://www.newsweek.com/list-vaccines-mandated-us-military-covid-1641228 |url-status=live |archive-url=https://web.archive.org/web/20231219004334/https://www.newsweek.com/list-vaccines-mandated-us-military-covid-1641228 |archive-date=December 19, 2023 |work=Newsweek}}

According to the CDC, the live attenuated virus (LAIV4) (which comes in the form of nasal spray in the US) should be avoided by some groups.{{cite web | title=Live Attenuated Influenza Vaccine [LAIV] (The Nasal Spray Flu Vaccine) | website=U.S. Centers for Disease Control and Prevention (CDC) | date=September 16, 2019 | url=https://www.cdc.gov/flu/prevent/nasalspray.htm | archive-url=https://web.archive.org/web/20191014221155/https://www.cdc.gov/flu/prevent/nasalspray.htm | archive-date=October 14, 2019 | url-status=live | access-date=October 14, 2019}} {{PD-notice}}

Within its blanket recommendation for general vaccination in the United States, the CDC, which began recommending the influenza vaccine to healthcare workers in 1981, emphasizes to clinicians the special urgency of vaccination for members of certain vulnerable groups, and their caregivers:

: Vaccination is especially important for people at higher risk of serious influenza complications or people who live with or care for people at higher risk for serious complications.{{cite web|url=https://www.cdc.gov/flu/professionals/vaccination/vax-summary.htm|title=Influenza Vaccination: A Summary for Clinicians – Health Professionals – Seasonal Influenza (Flu)|publisher=U.S. Centers for Disease Control and Prevention (CDC)|url-status=live|archive-url=https://web.archive.org/web/20080224040716/http://www.cdc.gov/flu/professionals/vaccination/vax-summary.htm|archive-date=February 24, 2008|date=September 6, 2018}} {{PD-notice}} In 2009, a new high-dose formulation of the standard influenza vaccine was approved.{{cite web | title=Fluzone, Fluzone High-Dose and Fluzone Intradermal | publisher=U.S. Food and Drug Administration (FDA) | url=https://www.fda.gov/vaccines-blood-biologics/vaccines/fluzone-fluzone-high-dose-and-fluzone-intradermal | date=July 11, 2017 | archive-date=July 22, 2017 | archive-url=https://wayback.archive-it.org/7993/20170722071642/https://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm112854.htm | url-status=live | access-date=June 1, 2020}} The Fluzone High Dose is specifically for people 65 and older; the difference is that it has four times the antigen dose of the standard Fluzone.{{cite journal | vauthors = Couch RB, Winokur P, Brady R, Belshe R, Chen WH, Cate TR, Sigurdardottir B, Hoeper A, Graham IL, Edelman R, He F, Nino D, Capellan J, Ruben FL | title = Safety and immunogenicity of a high dosage trivalent influenza vaccine among elderly subjects | journal = Vaccine | volume = 25 | issue = 44 | pages = 7656–63 | date = November 2007 | pmid = 17913310 | pmc = 2243220 | doi = 10.1016/j.vaccine.2007.08.042 }}{{cite journal |vauthors=Lee JK, Lam GK, Shin T, Kim J, Krishnan A, Greenberg DP, Chit A |title=Efficacy and effectiveness of high-dose versus standard-dose influenza vaccination for older adults: a systematic review and meta-analysis |journal=Expert Rev Vaccines |volume=17 |issue=5 |pages=435–443 |date=May 2018 |pmid=29715054 |doi=10.1080/14760584.2018.1471989 | s2cid=21688517 }}{{cite journal |vauthors=Robertson CA, DiazGranados CA, Decker MD, Chit A, Mercer M, Greenberg DP |title=Fluzone High-Dose Influenza Vaccine |journal=Expert Rev Vaccines |volume=15 |issue=12 |pages=1495–1505 |date=December 2016 |pmid=27813430 |doi=10.1080/14760584.2016.1254044 | doi-access = free | title-link = doi }}{{cite report |title=Literature review update on the efficacy and effectiveness of high-dose (Fluzone High-Dose) and MF59-adjuvanted (Fluad) trivalent inactivated influenza vaccines in adults 65 years of age and older |id=HP40-210/2018E-PDF |location=Ottawa |publisher=Public Health Agency of Canada |date=May 2018 |url=http://publications.gc.ca/collections/collection_2018/aspc-phac/HP40-210-2018-eng.pdf |access-date=June 1, 2020 |archive-date=July 21, 2020 |archive-url=https://web.archive.org/web/20200721210629/http://publications.gc.ca/collections/collection_2018/aspc-phac/HP40-210-2018-eng.pdf |url-status=live }}

The US government requires hospitals to report worker vaccination rates. Some US states and hundreds of US hospitals require healthcare workers to either get vaccinations or wear masks during flu season. These requirements occasionally engender union lawsuits on narrow collective bargaining grounds, but proponents note that courts have generally endorsed forced vaccination laws affecting the general population during disease outbreaks.{{cite web | vauthors = Tanner L |url= https://www.nbcnews.com/health/hospitals-crack-down-workers-who-refuse-flu-shots-1B7956764 |title=Hospitals crackdown on workers who refuse flu shots |publisher=NBC News |date=January 13, 2013 |access-date=July 24, 2014 |url-status=live |archive-url=https://web.archive.org/web/20131203052836/https://www.nbcnews.com/health/hospitals-crack-down-workers-who-refuse-flu-shots-1B7956764 |archive-date=December 3, 2013 }}

Vaccination against influenza is especially considered important for members of high-risk groups who would be likely to have complications from influenza, for example pregnant women{{cite journal | title = Seasonal influenza and 2009 H1N1 influenza vaccination coverage among pregnant women – 10 states, 2009–10 influenza season | journal = Morbidity and Mortality Weekly Report (MMWR)| volume = 59 | issue = 47 | pages = 1541–45 | date = December 2010 | pmid = 21124293 | url = https://www.cdc.gov/mmwr/pdf/wk/mm5947.pdf | archive-url = https://web.archive.org/web/20170625002726/https://www.cdc.gov/mmwr/PDF/wk/mm5947.pdf | url-status = live | archive-date = June 25, 2017 |author=Centers for Disease Control Prevention (CDC)}} {{PD-notice}} and children and teenagers from six months to 18 years of age who are receiving aspirin- or salicylate-containing medications and who might be at risk for experiencing Reye syndrome after influenza virus infection;

• In raising the upper age limit to 18 years, the aim is to reduce both the time children and parents lose from visits to pediatricians and missing school and the need for antibiotics for complications
• An added benefit expected from the vaccination of children is a reduction in the number of influenza cases among parents and other household members, and of possible spread to the general community.{{cite news| work = The New York Times| vauthors = Altman LK | date = February 28, 2008| title = Panel Advises Flu Shots for Children Up to Age 18| url = https://www.nytimes.com/2008/02/28/health/28flu.html| url-status = live| archive-url = https://web.archive.org/web/20150122091530/http://www.nytimes.com/2008/02/28/health/28flu.html| archive-date = January 22, 2015 }}

The CDC indicated that live attenuated influenza vaccine (LAIV), also called the nasal spray vaccine, was not recommended for the 2016–2017 flu season in the United States.{{cite press release|url=https://www.cdc.gov/media/releases/2016/s0622-laiv-flu.html|title=ACIP votes down use of LAIV for 2016–2017 flu season|date=June 22, 2016|access-date=November 26, 2016|publisher=U.S. Centers for Disease Control and Prevention (CDC)|url-status=live|archive-url=https://web.archive.org/web/20161125075847/http://www.cdc.gov/media/releases/2016/s0622-laiv-flu.html|archive-date=November 25, 2016}} {{PD-notice}}

Furthermore, the CDC recommends that healthcare personnel who care for severely immunocompromised persons receive injections (TIV or QIV) rather than LAIV.{{cite web|title=Immunization Schedules|url=https://www.cdc.gov/vaccines/schedules/hcp/imz/adult-conditions.html|publisher=U.S. Centers for Disease Control and Prevention (CDC)|access-date=November 4, 2014|url-status=live|archive-url=https://web.archive.org/web/20141105025622/http://www.cdc.gov/vaccines/schedules/hcp/imz/adult-conditions.html|archive-date=November 5, 2014}} {{PD-notice}}

The Australian Government recommends seasonal flu vaccination for everyone over the age of six months. Australia uses inactivated vaccines.{{cite web|title=Flu vaccine FAQs|url=https://www.healthdirect.gov.au/flu-vaccine-faqs|publisher=Healthdirect, Department of Health, Government of Australia|access-date=May 29, 2019|date=April 1, 2019|archive-date=May 29, 2019|archive-url=https://web.archive.org/web/20190529043146/https://www.healthdirect.gov.au/flu-vaccine-faqs|url-status=live}} Until 2021, the egg-based vaccine has been the only one available (and continues to be the only free one), but from March 2021 a new cell-based vaccine is available for those who wish to pay for it, and it is expected that this one will become the standard by 2026.

The standard flu vaccine is free for the following people:{{cite web|title=Influenza fact sheet|url=https://www.health.nsw.gov.au/Infectious/factsheets/Pages/influenza_factsheet.aspx|publisher=Healthdirect, Department of Health, Government of Australia|access-date=May 29, 2019|date=April 1, 2019|archive-date=May 29, 2019|archive-url=https://web.archive.org/web/20190529043157/https://www.health.nsw.gov.au/Infectious/factsheets/Pages/influenza_factsheet.aspx|url-status=live}}

• children aged six months to five years;
• people aged 65 years and over;
• Aboriginal and Torres Strait Islander people aged six months and over;
• pregnant women; and
• anyone over six months of age with medical conditions such as severe asthma, lung disease or heart disease, low immunity, or diabetes that can lead to complications from influenza.

Uptake of flu vaccination, both seasonally and during pandemics, is often low.{{cite journal | vauthors = Han YK, Michie S, Potts HW, Rubin GJ | title = Predictors of influenza vaccine uptake during the 2009/10 influenza A H1N1v ('swine flu') pandemic: Results from five national surveys in the United Kingdom | journal = Preventive Medicine | volume = 84 | pages = 57–61 | date = March 2016 | pmid = 26757401 | pmc = 4766366 | doi = 10.1016/j.ypmed.2015.12.018 }} Systematic reviews of pandemic flu vaccination uptake have identified several personal factors that may influence uptake, including gender (higher uptake in men), ethnicity (higher in people from ethnic minorities), and having a chronic illness.{{cite journal | vauthors = Bish A, Yardley L, Nicoll A, Michie S | title = Factors associated with uptake of vaccination against pandemic influenza: a systematic review | journal = Vaccine | volume = 29 | issue = 38 | pages = 6472–84 | date = September 2011 | pmid = 21756960 | doi = 10.1016/j.vaccine.2011.06.107 }}{{cite journal | vauthors = Brien S, Kwong JC, Buckeridge DL | title = The determinants of 2009 pandemic A/H1N1 influenza vaccination: a systematic review | journal = Vaccine | volume = 30 | issue = 7 | pages = 1255–64 | date = February 2012 | pmid = 22214889 | doi = 10.1016/j.vaccine.2011.12.089 }} Beliefs in the safety and effectiveness of the vaccine are also important.

Several measures are useful to increase rates of vaccination in those over sixty including patient reminders using leaflets and letters, postcard reminders, client outreach programs, vaccine home visits, group vaccinations, free vaccinations, physician payment, physician reminders, and encouraging physician competition.{{cite journal | vauthors = Thomas RE, Lorenzetti DL | title = Interventions to increase influenza vaccination rates of those 60 years and older in the community | journal = The Cochrane Database of Systematic Reviews | volume = 5 | page = CD005188 | date = May 2018 | pmid = 29845606 | pmc = 6494593 | doi = 10.1002/14651858.CD005188.pub4 | doi-access = free | title-link = doi | issue = 5 }}

Frontline healthcare workers are often recommended to get seasonal and any pandemic flu vaccinations. For example, in the UK all healthcare workers involved in patient care are recommended to receive the seasonal flu vaccine, and were also recommended to be vaccinated against the H1N1/09 (later renamed A(H1N1)pdm09(H1N1)pdm09 is newer nomenclature for the 2009 pandemic H1N1 virus, not a different strain.{{cite journal | title = Update on influenza A (H1N1) 2009 monovalent vaccines | journal = Morbidity and Mortality Weekly Report (MMWR)| volume = 58 | issue = 39 | pages = 1100–01 | date = October 2009 | pmid = 19816398 | url = https://www.cdc.gov/mmwr/pdf/wk/mm5839.pdf | archive-url = https://web.archive.org/web/20110629132344/http://www.cdc.gov/mmwr/pdf/wk/mm5839.pdf | url-status = live | archive-date = June 29, 2011 |author=Centers for Disease Control Prevention (CDC)}} {{PD-notice}}) swine flu virus during the 2009 pandemic. However, uptake is often low.{{cite journal | vauthors = Rubin GJ, Potts HW, Michie S | title = Likely uptake of swine and seasonal flu vaccines among healthcare workers. A cross-sectional analysis of UK telephone survey data | journal = Vaccine | volume = 29 | issue = 13 | pages = 2421–28 | date = March 2011 | pmid = 21277402 | doi = 10.1016/j.vaccine.2011.01.035 }} During the 2009 pandemic, low uptake by healthcare workers was seen in countries including the UK, Italy,{{cite journal | vauthors = La Torre G, Di Thiene D, Cadeddu C, Ricciardi W, Boccia A | title = Behaviours regarding preventive measures against pandemic H1N1 influenza among Italian healthcare workers, October 2009 | journal = Euro Surveillance | volume = 14 | issue = 49 | date = December 2009 | pmid = 20003908 }} Greece,{{cite journal | vauthors = Amodio E, Anastasi G, Marsala MG, Torregrossa MV, Romano N, Firenze A | title = Vaccination against the 2009 pandemic influenza A (H1N1) among healthcare workers in the major teaching hospital of Sicily (Italy) | journal = Vaccine | volume = 29 | issue = 7 | pages = 1408–12 | date = February 2011 | pmid = 21199700 | doi = 10.1016/j.vaccine.2010.12.041 }} and Hong Kong.{{cite journal | vauthors = Chor JS, Ngai KL, Goggins WB, Wong MC, Wong SY, Lee N, Leung TF, Rainer TH, Griffiths S, Chan PK | title = Willingness of Hong Kong healthcare workers to accept pre-pandemic influenza vaccination at different WHO alert levels: two questionnaire surveys | journal = BMJ | volume = 339 | page = b3391 | date = August 2009 | pmid = 19706937 | pmc = 2731837 | doi = 10.1136/bmj.b3391 }}

In a 2010 survey of United States healthcare workers, 63.5% reported that they received the flu vaccine during the 2010–11 season, an increase from 61.9% reported the previous season. US Health professionals with direct patient contact had higher vaccination uptake, such as physicians and dentists (84.2%) and nurse practitioners (82.6%).{{cite web | title=CDC updates flu vaccination recommendations | vauthors = Schnirring L | website=Center for Infectious Disease Research and Policy (CIDRAP) | date=August 18, 2011| url=http://www.cidrap.umn.edu/news-perspective/2011/08/cdc-updates-flu-vaccination-recommendations | archive-url=https://web.archive.org/web/20191025025948/http://www.cidrap.umn.edu/news-perspective/2011/08/cdc-updates-flu-vaccination-recommendations | archive-date=October 25, 2019 | url-status=live | access-date=October 24, 2019 }}{{cite journal | title = Influenza vaccination coverage among health-care personnel – United States, 2010–11 influenza season | journal = Morbidity and Mortality Weekly Report (MMWR)| volume = 60 | issue = 32 | pages = 1073–77 | date = August 2011 | pmid = 21849963 | url = https://www.cdc.gov/mmwr/pdf/wk/mm6032.pdf | archive-url = https://web.archive.org/web/20170525220229/https://www.cdc.gov/mmwr/pdf/wk/mm6032.pdf | url-status = live | archive-date = May 25, 2017 |author=Centers for Disease Control Prevention (CDC)}} {{PD-notice}}{{cite journal | title = Influenza vaccination coverage among health-care personnel: 2011–12 influenza season, United States | journal = Morbidity and Mortality Weekly Report (MMWR)| volume = 61 | pages = 753–57 | date = September 2012 | pmid = 23013720 | url = https://www.cdc.gov/mmwr/pdf/wk/mm6138.pdf | archive-url = https://web.archive.org/web/20170624221955/https://www.cdc.gov/mmwr/PDF/wk/mm6138.pdf | url-status = live | archive-date = June 24, 2017 |author=Centers for Disease Control Prevention (CDC)}} {{PD-notice}}

The main reason to vaccinate health care workers is to prevent staff from spreading flu to their patients and to reduce staff absence at a time of high service demand, but the reasons health care workers state for their decisions to accept or decline vaccination may more often be to do with perceived personal benefits.

In Victoria (Australia) public hospitals, rates of healthcare worker vaccination in 2005 ranged from 34% for non-clinical staff to 42% for laboratory staff. One of the reasons for rejecting vaccines was concern over adverse reactions; in one study, 31% of resident physicians at a teaching hospital incorrectly believed Australian vaccines could cause influenza.{{cite journal | vauthors = Bull AL, Bennett N, Pitcher HC, Russo PL, Richards MJ | title = Influenza vaccine coverage among health care workers in Victorian public hospitals | journal = The Medical Journal of Australia | volume = 186 | issue = 4 | pages = 185–86 | date = February 2007 | pmid = 17309419 | doi = 10.5694/j.1326-5377.2007.tb00858.x | s2cid = 25091208 }}

File:Reassortment.svg of influenza vaccine creation]]

Research continues into the idea of a "universal" influenza vaccine that would not require tailoring to a particular strain, but would be effective against a broad variety of influenza viruses.{{cite journal | vauthors = Abbasi J | title = The Search for a Universal Flu Vaccine Heats Up | journal = JAMA | volume = 322 | issue = 20 | pages = 1942–1944 | date = November 2019 | pmid = 31693060 | doi = 10.1001/jama.2019.16816 | s2cid = 207903441 }} No vaccine candidates had been announced by November 2007,{{cite AV media | vauthors = Greenfieldboyce N | title=New and Old Ways to Make Flu Vaccines | publisher=NPR | date=November 8, 2007 | url=https://www.npr.org/templates/story/story.php?storyId=16105360 | archive-url=https://web.archive.org/web/20191024052018/https://www.npr.org/templates/story/story.php?storyId=16105360 | archive-date=October 24, 2019 | url-status=live | access-date=October 23, 2019 | medium=Radio broadcast }} but {{as of|lc=yes|2021}}, there are several universal vaccines candidates, in pre-clinical development and in clinical trials.{{cite journal | vauthors = Nachbagauer R, Krammer F | title = Universal influenza virus vaccines and therapeutic antibodies | journal = Clinical Microbiology and Infection | volume = 23 | issue = 4 | pages = 222–228 | date = April 2017 | pmid = 28216325 | pmc = 5389886 | doi = 10.1016/j.cmi.2017.02.009 }}{{Cite web |title=First-in-human universal flu vaccine trial begins |vauthors=Balfour H |website=European Pharmaceutical Review |date=June 2, 2021 |url=https://www.europeanpharmaceuticalreview.com/news/155806/first-in-human-universal-flu-vaccine-trial-begins/ |quote=The Phase I trial (NCT04896086) will assess the safety and immunogenicity of the experimental vaccine, FluMos-v1 |access-date=February 6, 2022 |archive-date=March 29, 2022 |archive-url=https://web.archive.org/web/20220329214713/https://www.europeanpharmaceuticalreview.com/news/155806/first-in-human-universal-flu-vaccine-trial-begins/ |url-status=live }}{{cite journal | vauthors = Bernstein DI, Guptill J, Naficy A, Nachbagauer R, Berlanda-Scorza F, Feser J, Wilson PC, Solórzano A, Van der Wielen M, Walter EB, Albrecht RA, Buschle KN, Chen YQ, Claeys C, Dickey M, Dugan HL, Ermler ME, Freeman D, Gao M, Gast C, Guthmiller JJ, Hai R, Henry C, Lan LY, McNeal M, Palm AE, Shaw DG, Stamper CT, Sun W, Sutton V, Tepora ME, Wahid R, Wenzel H, Wohlbold TJ, Innis BL, García-Sastre A, Palese P, Krammer F | title = Immunogenicity of chimeric haemagglutinin-based, universal influenza virus vaccine candidates: interim results of a randomised, placebo-controlled, phase 1 clinical trial | journal = The Lancet. Infectious Diseases | volume = 20 | issue = 1 | pages = 80–91 | date = January 2020 | pmid = 31630990 | pmc = 6928577 | doi = 10.1016/S1473-3099(19)30393-7 | doi-access = free | title-link = doi }}{{cite journal | vauthors = Nachbagauer R, Feser J, Naficy A, Bernstein DI, Guptill J, Walter EB, Berlanda-Scorza F, Stadlbauer D, Wilson PC, Aydillo T, Behzadi MA, Bhavsar D, Bliss C, Capuano C, Carreño JM, Chromikova V, Claeys C, Coughlan L, Freyn AW, Gast C, Javier A, Jiang K, Mariottini C, McMahon M, McNeal M, Solórzano A, Strohmeier S, Sun W, Van der Wielen M, Innis BL, García-Sastre A, Palese P, Krammer F | title = A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial | journal = Nature Medicine | volume = 27 | issue = 1 | pages = 106–114 | date = January 2021 | pmid = 33288923 | doi = 10.1038/s41591-020-1118-7 | doi-access = free | title-link = doi }}

In a 2007 report, the global capacity of approximately 826 million seasonal influenza vaccine doses (inactivated and live) was double the production of 413 million doses. In an aggressive scenario of producing pandemic influenza vaccines by 2013, only 2.8 billion courses could be produced in a six-month time frame. If all high- and upper-middle-income countries sought vaccines for their entire populations in a pandemic, nearly two billion courses would be required. If China pursued this goal as well, more than three billion courses would be required to serve these populations.{{cite web |url=https://path.org/resources/influenza-vaccine-strategies-for-broad-global-access/ |title=Influenza Vaccine Strategies for Broad Global Access | website=Path | date=October 2007 | access-date=September 16, 2009 |url-status=live |archive-url=https://web.archive.org/web/20191014212233/https://path.org/resources/influenza-vaccine-strategies-for-broad-global-access/ |archive-date=October 14, 2019 }} Vaccine research and development is ongoing to identify novel vaccine approaches that could produce much greater quantities of vaccine at a price that is affordable to the global population.{{citation needed|date=June 2019}}

Most flu vaccines are grown by vaccine manufacturers in fertilized chicken eggs.{{cite web|url=http://www.ecbt.org/parents/media/pdf/howisflumade.pdf|archive-url=https://web.archive.org/web/20100705162154/http://www.ecbt.org/parents/media/pdf/howisflumade.pdf|archive-date=July 5, 2010|title=how it's made}} In the Northern hemisphere, the manufacturing process begins following the announcement (typically in February) of the WHO recommended strains for the winter flu season.{{cite web|url=https://www.who.int/influenza/vaccines/virus/en/|title=Influenza vaccine viruses and reagents|publisher=World Health Organization (WHO)|archive-url=https://web.archive.org/web/20130527161247/http://www.who.int/influenza/vaccines/virus/en/|archive-date=May 27, 2013}} Three strains (representing an H1N1, an H3N2, and a B strain) of flu are selected and chicken eggs are inoculated separately. These monovalent harvests are then combined to make the trivalent vaccine.{{cite web|title=Recommendations for the production and control of influenza vaccine (inactivated)|url=https://www.who.int/biologicals/publications/trs/areas/vaccines/influenza/ANNEX%203%20InfluenzaP99-134.pdf|publisher=World Health Organization (WHO)|access-date=May 27, 2013|url-status=live|archive-url=https://web.archive.org/web/20131028160256/http://www.who.int/biologicals/publications/trs/areas/vaccines/influenza/ANNEX%203%20InfluenzaP99-134.pdf|archive-date=October 28, 2013}}

File:ReverseGeneticsFlu.svg

{{As of|2007|11}}, both the conventional injection and the nasal spray are manufactured using chicken eggs. The European Union also approved Optaflu, a vaccine produced by Novartis using vats of animal cells. This technique is expected to be more scalable and avoid problems with eggs, such as allergic reactions and incompatibility with strains that affect avians like chickens.

Influenza vaccines are produced in pathogen-free eggs that are eleven or twelve days old.{{cite web| url = http://www.virology.ws/2009/12/10/influenza-virus-growth-in-eggs/| vauthors = Racaniello V | title = Influenza virus growth in eggs| publisher = Virology Blog| date = Dec 2009| url-status = live| archive-url = https://web.archive.org/web/20141225163841/http://www.virology.ws/2009/12/10/influenza-virus-growth-in-eggs/| archive-date = December 25, 2014 }} The top of the egg is disinfected by wiping it with alcohol and then the egg is candled to identify a non-veinous area in the allantoic cavity where a small hole is poked to serve as a pressure release.{{cite web| url = https://www.youtube.com/watch?v=766QH_qaYN8| vauthors = Izzat F | title = Viral Cultivation in Chicken Embryo| publisher = Youtube| date = Apr 2012| url-status = live| archive-url = https://web.archive.org/web/20150526061454/https://www.youtube.com/watch?v=766QH_qaYN8| archive-date = May 26, 2015 }} A second hole is made at the top of the egg, where the influenza virus is injected in the allantoic cavity, past the chorioallantoic membrane. The two holes are then sealed with melted paraffin and the inoculated eggs are incubated for 48 hours at 37 degrees Celsius. During the incubation time, the virus replicates and newly replicated viruses are released into the allantoic fluid{{cite web| url = https://www.cdc.gov/flu/prevent/how-fluvaccine-made.htm | title = How Influenza (Flu) Vaccines Are Made | publisher = U.S. Centers for Disease Control and Prevention (CDC) | date = November 26, 2019 | archive-url = https://web.archive.org/web/20191202211729/https://www.cdc.gov/flu/prevent/how-fluvaccine-made.htm | archive-date = December 2, 2019 | url-status = live | access-date = December 2, 2019 }} {{PD-notice}}

After the 48-hour incubation period, the top of the egg is cracked and ten milliliters of allantoic fluid is removed, from which about fifteen micrograms of the flu vaccine can be obtained. At this point, the viruses have been weakened or killed and the viral antigen is purified and placed inside vials, syringes, or nasal sprayers. Up to 3 eggs are needed to produce one dose of a trivalent vaccine, and an estimated 600 million eggs are produced each year for flu vaccine production.{{Cite web |vauthors=Seemann G, Kock M |date=2008 |title=Fertile eggs – a valuable product for vaccine production |url=https://lohmann-breeders.com/lohmanninfo/fertile-eggs-a-valuable-product-for-vaccine-production/ |access-date=October 19, 2023 |website=Lohmann Breeders |archive-date=November 23, 2023 |archive-url=https://web.archive.org/web/20231123222125/https://lohmann-breeders.com/lohmanninfo/fertile-eggs-a-valuable-product-for-vaccine-production/ |url-status=live }}

Methods of vaccine generation that bypass the need for eggs include the construction of influenza virus-like particles (VLP). VLP resemble viruses, but there is no need for inactivation, as they do not include viral coding elements, but merely present antigens in a similar manner to a virion. Some methods of producing VLP include cultures of Spodoptera frugiperda Sf9 insect cells and plant-based vaccine production (e.g., production in Nicotiana benthamiana). There is evidence that some VLPs elicit antibodies that recognize a broader panel of antigenically distinct viral isolates compared to other vaccines in the hemagglutination-inhibition assay (HIA).{{cite journal | vauthors = Bright RA, Carter DM, Daniluk S, Toapanta FR, Ahmad A, Gavrilov V, Massare M, Pushko P, Mytle N, Rowe T, Smith G, Ross TM | title = Influenza virus-like particles elicit broader immune responses than whole virion inactivated influenza virus or recombinant hemagglutinin | journal = Vaccine | volume = 25 | issue = 19 | pages = 3871–78 | date = May 2007 | pmid = 17337102 | doi = 10.1016/j.vaccine.2007.01.106 }}

A gene-based DNA vaccine, used to prime the immune system after boosting with an inactivated H5N1 vaccine, underwent clinical trials in 2011.{{cite web |url=http://www.nih.gov/news/health/oct2011/niaid-03.htm |title=Priming with DNA vaccine makes avian flu vaccine work better (NIH News) |date=October 3, 2011 |url-status=live |archive-url=https://web.archive.org/web/20120927233909/http://www.nih.gov/news/health/oct2011/niaid-03.htm |archive-date=September 27, 2012 }}{{ClinicalTrialsGov|NCT00776711|Vaccine for Prevention of Bird Flu}}{{ClinicalTrialsGov|NCT01086657|An Open-Label, Randomized Phase{{spaces}}I Study in Healthy Adults of the Safety and Immunogenicity of Prime-Boost Intervals with Monovalent Influenza Subunit Virion (H5N1) Vaccine, A/Indonesia/05/2005 (Sanofi Pasteur, Inc), Administered Alone or Following Recombinant DNA Plasmid (H5) Vaccine, VRC-AVIDNA036-00-VP (VRC, NIAID)}}

In November 2012, Novartis received FDA approval for the first cell-culture vaccine.{{cite press release|url=https://www.prnewswire.com/news-releases/novartis-receives-fda-approval-for-flucelvax-the-first-cell-culture-vaccine-in-us-to-help-protect-against-seasonal-influenza-180239401.html |archive-url=https://web.archive.org/web/20121128072149/http://www.novartis.com/newsroom/media-releases/en/2012/1659272.shtml |url-status=live |archive-date=November 28, 2012 |title=Novartis receives FDA approval for Flucelvax, the first cell-culture vaccine in US to help protect against seasonal influenza |publisher=Novartis |date=November 20, 2012 }}{{cite press release|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm328982.htm|title=FDA approves first seasonal influenza vaccine manufactured using cell culture technology|publisher=U.S. Food and Drug Administration (FDA)|archive-url=https://web.archive.org/web/20130102094936/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm328982.htm|archive-date=January 2, 2013}} {{PD-notice}}{{cite web|url=https://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm328684.htm|title=Approved Products – November 20, 2012 Approval Letter – Flucelvax| author = Center for Biologics Evaluation and Research |publisher=U.S. Food and Drug Administration (FDA)|archive-url=https://web.archive.org/web/20121203114226/https://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm328684.htm|archive-date=December 3, 2012}} {{PD-notice}}{{cite press release | title = Seqirus receives FDA approval for Flucelvax Quadrivalent (Influenza Vaccine) for people four years of age and older | url = http://www.seqirus.com/newsroom/FDA-approval-FLUCELVAX-QUADRIVALENT | publisher = Seqirus | date = May 23, 2016 | archive-url = https://web.archive.org/web/20170116163927/http://www.seqirus.com/newsroom/FDA-approval-FLUCELVAX-QUADRIVALENT | archive-date = January 16, 2017 | access-date = January 15, 2017 }} In 2013, the recombinant influenza vaccine, Flublok, was approved for use in the United States.{{cite web | title=FDA approves first flu vaccine grown in insect cells | vauthors = Roos R | website=Center for Infectious Disease Research and Policy (CIDRAP) | date=October 14, 2019 | url=http://www.cidrap.umn.edu/news-perspective/2013/01/fda-approves-first-flu-vaccine-grown-insect-cells | archive-url=https://web.archive.org/web/20191014200136/http://www.cidrap.umn.edu/news-perspective/2013/01/fda-approves-first-flu-vaccine-grown-insect-cells | archive-date=October 14, 2019 | url-status=live | access-date=October 14, 2019 }}{{cite web | title=Flublok | publisher= U.S. Food and Drug Administration (FDA) | date=February 26, 2018 | url=https://www.fda.gov/vaccines-blood-biologics/vaccines/flublok | archive-url=https://web.archive.org/web/20191014200957/https://www.fda.gov/vaccines-blood-biologics/vaccines/flublok | archive-date=October 14, 2019 | url-status=live | access-date=October 14, 2019 | id= STN 125285}} {{PD-notice}}{{cite web | title=Flublok Quadrivalent | publisher= U.S. Food and Drug Administration (FDA) | date=August 2, 2019 | url=https://www.fda.gov/vaccines-blood-biologics/vaccines/flublok-quadrivalent | archive-url=https://web.archive.org/web/20191014201325/https://www.fda.gov/vaccines-blood-biologics/vaccines/flublok-quadrivalent | archive-date=October 14, 2019 | url-status=live | access-date=October 14, 2019 | id= STN 125285}} {{PD-notice}}

On September 17, 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for Supemtek, a quadrivalent influenza vaccine (recombinant, prepared in cell culture).{{cite web | title=Supemtek: Pending EC decision | website=European Medicines Agency (EMA) | date=September 17, 2020 | url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/supemtek | access-date=September 21, 2020 | archive-date=September 23, 2020 | archive-url=https://web.archive.org/web/20200923005908/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/supemtek | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. The applicant for this medicinal product is Sanofi Pasteur. Supemtek was authorized for medical use in the European Union in November 2020.{{cite web | title=Supemtek EPAR | website=European Medicines Agency (EMA) | date=September 15, 2020 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/supemtek | access-date=November 27, 2020 | archive-date=January 10, 2021 | archive-url=https://web.archive.org/web/20210110092717/https://www.ema.europa.eu/en/medicines/human/EPAR/supemtek | url-status=live }}{{cite web | title=Supemtek Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1484.htm | access-date=March 3, 2023 | archive-date=March 5, 2023 | archive-url=https://web.archive.org/web/20230305052137/https://ec.europa.eu/health/documents/community-register/html/h1484.htm | url-status=live }}

Australia authorized its first cell-based vaccine in March 2021, based on an "eternal cell line" of a dog kidney. Because of the way it is produced, it produces better-matched vaccines (to the flu strains).

According to the WHO, {{as of|2019|lc=yes}}, countries where influenza vaccine is produced include:{{cite journal | vauthors = Sparrow E, Wood JG, Chadwick C, Newall AT, Torvaldsen S, Moen A, Torelli G | title = Global production capacity of seasonal and pandemic influenza vaccines in 2019 | journal = Vaccine | volume = 39 | issue = 3 | pages = 512–520 | date = January 2021 | pmid = 33341308 | pmc = 7814984 | doi = 10.1016/j.vaccine.2020.12.018 }}

{{columns list|colwidth=20em|

• Australia
• Brazil
• Canada
• China
• France
• Germany
• Hungary
• India
• Iran
• Japan
• Mexico
• Netherlands
• Nicaragua
• Russian Federation
• South Korea
• United Kingdom
• United States
• Vietnam

}}

In addition, Kazakhstan, Serbia, and Thailand had facilities in the final stages of establishing production.

The cost-effectiveness of seasonal influenza vaccination has been widely evaluated for different groups and in different settings.{{cite journal | vauthors = Jit M, Newall AT, Beutels P | title = Key issues for estimating the impact and cost-effectiveness of seasonal influenza vaccination strategies | journal = Human Vaccines & Immunotherapeutics | volume = 9 | issue = 4 | pages = 834–40 | date = April 2013 | pmid = 23357859 | pmc = 3903903 | doi = 10.4161/hv.23637 }} In the elderly (over 65), the majority of published studies have found that vaccination is cost-saving, with the cost savings associated with influenza vaccination (e.g. prevented health care visits) outweighing the cost of vaccination.{{cite journal | vauthors = Postma MJ, Baltussen RP, Palache AM, Wilschut JC | title = Further evidence for favorable cost-effectiveness of elderly influenza vaccination | journal = Expert Review of Pharmacoeconomics & Outcomes Research | volume = 6 | issue = 2 | pages = 215–27 | date = April 2006 | pmid = 20528557 | doi = 10.1586/14737167.6.2.215 | s2cid = 12765724 }} In older adults (aged 50–64 years), several published studies have found that influenza vaccination is likely to be cost-effective, however, the results of these studies were often found to be dependent on key assumptions used in the economic evaluations.{{cite journal | vauthors = Newall AT, Kelly H, Harsley S, Scuffham PA | title = Cost effectiveness of influenza vaccination in older adults: a critical review of economic evaluations for the 50- to 64-year age group | journal = PharmacoEconomics | volume = 27 | issue = 6 | pages = 439–50 | year = 2009 | pmid = 19640008 | doi = 10.2165/00019053-200927060-00001 | s2cid = 20855671 | doi-access = free }} The uncertainty in influenza cost-effectiveness models can partially be explained by the complexities involved in estimating the disease burden,{{cite journal | vauthors = Newall AT, Viboud C, Wood JG | title = Influenza-attributable mortality in Australians aged more than 50 years: a comparison of different modelling approaches | journal = Epidemiology and Infection | volume = 138 | issue = 6 | pages = 836–42 | date = June 2010 | pmid = 19941685 | doi = 10.1017/S095026880999118X | s2cid = 29939376 | doi-access = free }} as well as the seasonal variability in the circulating strains and the match of the vaccine.{{cite journal | vauthors = Newall AT, Dehollain JP, Creighton P, Beutels P, Wood JG | title = Understanding the cost-effectiveness of influenza vaccination in children: methodological choices and seasonal variability | journal = PharmacoEconomics | volume = 31 | issue = 8 | pages = 693–702 | date = August 2013 | pmid = 23645539 | doi = 10.1007/s40273-013-0060-7 | s2cid = 8616720 | doi-access = free }}{{cite journal | vauthors = Newall AT, Scuffham PA | title = Uncertainty and variability in influenza cost-effectiveness models | journal = Australian and New Zealand Journal of Public Health | volume = 35 | issue = 6 | pages = 576; author reply 576–77 | date = December 2011 | pmid = 22151168 | doi = 10.1111/j.1753-6405.2011.00788.x | s2cid = 22402257 | doi-access = | title-link = doi }} In healthy working adults (aged 18–49 years), a 2012 review found that vaccination was generally not cost-saving, with the suitability for funding being dependent on the willingness to pay to obtain the associated health benefits.{{cite journal | vauthors = Gatwood J, Meltzer MI, Messonnier M, Ortega-Sanchez IR, Balkrishnan R, Prosser LA | title = Seasonal influenza vaccination of healthy working-age adults: a review of economic evaluations | journal = Drugs | volume = 72 | issue = 1 | pages = 35–48 | date = January 2012 | pmid = 22191794 | doi = 10.2165/11597310-000000000-00000 | s2cid = 46305863 }} In children, the majority of studies have found that influenza vaccination was cost-effective, however many of the studies included (indirect) productivity gains, which may not be given the same weight in all settings.{{cite journal | vauthors = Newall AT, Jit M, Beutels P | title = Economic evaluations of childhood influenza vaccination: a critical review | journal = PharmacoEconomics | volume = 30 | issue = 8 | pages = 647–60 | date = August 2012 | pmid = 22788257 | doi = 10.2165/11599130-000000000-00000 | s2cid = 38289883 | doi-access = free }} Several studies have attempted to predict the cost-effectiveness of interventions (including pre-pandemic vaccination) to help protect against a future pandemic, however estimating the cost-effectiveness has been complicated by uncertainty as to the severity of a potential future pandemic and the efficacy of measures against it.{{cite journal | vauthors = Newall AT, Wood JG, Oudin N, MacIntyre CR | title = Cost-effectiveness of pharmaceutical-based pandemic influenza mitigation strategies | journal = Emerging Infectious Diseases | volume = 16 | issue = 2 | pages = 224–30 | date = February 2010 | pmid = 20113551 | pmc = 2957998 | doi = 10.3201/eid1602.090571 }}

Influenza research includes molecular virology, molecular evolution, pathogenesis, host immune responses, genomics, and epidemiology. These help in developing influenza countermeasures such as vaccines, therapies, and diagnostic tools. Improved influenza countermeasures require basic research on how viruses enter cells, replicate, mutate, evolve into new strains, and induce an immune response. The Influenza Genome Sequencing Project is creating a library of influenza sequences{{cite web|title=Influenza Genome Sequencing Project – Overview|url=http://www.niaid.nih.gov/LabsAndResources/resources/dmid/gsc/Influenza/Pages/overview.aspx|archive-url=https://web.archive.org/web/20110627202613/http://www.niaid.nih.gov/LABSANDRESOURCES/RESOURCES/DMID/GSC/INFLUENZA/Pages/overview.aspx|archive-date=June 27, 2011|publisher=National Institutes of Health – National Institute of Allergy and Infectious Diseases|access-date=May 27, 2013}} that will help researchers' understanding of what makes one strain more lethal than another, what genetic determinants most affect immunogenicity, and how the virus evolves.

A different approach uses Internet content to estimate the impact of an influenza vaccination campaign. More specifically, researchers have used data from Twitter and Microsoft's Bing search engine and proposed a statistical framework that, after a series of operations, maps this information to estimates of the influenza-like illness reduction percentage in areas where vaccinations have been performed. The method has been used to quantify the impact of two flu vaccination programmes in England (2013/14 and 2014/15), where school-age children were administered a live attenuated influenza vaccine (LAIV). Notably, the impact estimates were in accordance with estimations from Public Health England based on traditional syndromic surveillance endpoints.{{cite journal |vauthors=Lampos V, Yom-Tov E, Pebody R, Cox IJ |doi=10.1007/s10618-015-0427-9 |title=Assessing the impact of a health intervention via user-generated Internet content |journal=Data Mining and Knowledge Discovery |volume=29 |issue=5 |pages=1434–57 |year=2015 |s2cid=215415165 |url=http://discovery.ucl.ac.uk/1469803/13/Assessing%20the%20impact%20of%20a%20health%20intervention%20via%20user-generated%20Internet%20content.pdf |doi-access=free |title-link=doi |access-date=August 15, 2022 |archive-date=August 28, 2021 |archive-url=https://web.archive.org/web/20210828124651/http://discovery.ucl.ac.uk/id/eprint/1469803/13/Assessing |url-status=live }}{{cite journal | vauthors = Wagner M, Lampos V, Yom-Tov E, Pebody R, Cox IJ | title = Estimating the Population Impact of a New Pediatric Influenza Vaccination Program in England Using Social Media Content | journal = Journal of Medical Internet Research | volume = 19 | issue = 12 | page = e416 | date = December 2017 | pmid = 29269339 | pmc = 6257312 | doi = 10.2196/jmir.8184 | doi-access = free }}

The rapid development, production, and distribution of pandemic influenza vaccines could potentially save millions of lives during an influenza pandemic. Due to the short time frame between the identification of a pandemic strain and the need for vaccination, researchers are looking at novel technologies for vaccine production that could provide better "real-time" access and be produced more affordably, thereby increasing access for people living in low- and moderate-income countries, where an influenza pandemic may likely originate, such as live attenuated (egg-based or cell-based) technology and recombinant technologies (proteins and virus-like particles).{{cite web |url=https://www.who.int/vaccine_research/diseases/ari/en/index1.html |title=Acute Respiratory Infections (Update September 2009) | date=September 2009 |publisher=World Health Organization (WHO) |access-date=September 16, 2009 |archive-url=https://web.archive.org/web/20090929200824/http://www.who.int/vaccine_research/diseases/ari/en/index1.html |archive-date=September 29, 2009 }} {{As of|July 2009}}, more than seventy known clinical trials have been completed or are ongoing for pandemic influenza vaccines.{{cite web |url=https://www.who.int/vaccine_research/immunogenicity/immunogenicity_table.xls |title=Tables on the Clinical trials of pandemic influenza prototype vaccines | date=July 2009 |publisher=World Health Organization (WHO)|access-date=September 21, 2009 |archive-url=https://web.archive.org/web/20090306161241/http://www.who.int/vaccine_research/immunogenicity/immunogenicity_table.xls |archive-date=March 6, 2009 }} In September 2009, the FDA approved four vaccines against the 2009 H1N1 influenza virus (the 2009 pandemic strain), and expected the initial vaccine lots to be available within the following month.{{cite press release |url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm182399.htm |title=FDA Approves Vaccines for 2009 H1N1 Influenza Virus |date=September 15, 2009 |access-date=October 15, 2009 |archive-url=https://web.archive.org/web/20091015083833/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm182399.htm |archive-date=October 15, 2009 }} {{PD-notice}}

In January 2020, the US Food and Drug Administration (FDA) approved Audenz as a vaccine for the H5N1 flu virus.{{cite web | vauthors=Keown A | title=FDA Approves Seqirus' Audenz as Vaccine Against Potential Flu Pandemic | website=BioSpace | date=February 4, 2020 | url=https://www.biospace.com/article/seqirus-wins-fda-approval-of-vaccine-for-potential-flu-pandemic/ | access-date=February 5, 2020 | archive-date=February 5, 2020 | archive-url=https://web.archive.org/web/20200205184348/https://www.biospace.com/article/seqirus-wins-fda-approval-of-vaccine-for-potential-flu-pandemic/ | url-status=live }} Audenz is a vaccine indicated for active immunization for the prevention of disease caused by the influenza A virus H5N1 subtype contained in the vaccine. Audenz is approved for use in persons six months of age and older at increased risk of exposure to the influenza A virus H5N1 subtype contained in the vaccine.{{cite web | title=Audenz | publisher=U.S. Food and Drug Administration (FDA) | date=January 31, 2020 | url=http://www.fda.gov/vaccines-blood-biologics/audenz | access-date=February 5, 2020 | id=STN: 125692 | archive-date=August 6, 2020 | archive-url=https://web.archive.org/web/20200806022227/https://www.fda.gov/vaccines-blood-biologics/audenz | url-status=live }} {{PD-notice}}

Zoonotic influenza vaccine Seqirus is authorized for use in the European Union.{{cite web | title=Zoonotic Influenza Vaccine Seqirus EPAR | website=European Medicines Agency (EMA) | date=9 October 2023 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/zoonotic-influenza-vaccine-seqirus | access-date=26 September 2024}} It is an H5N8 vaccine that is intended to provide acquired immunity against H5 subtype influenza A viruses.

{{Main|Universal flu vaccine}}

A universal influenza vaccine that would not have to be designed and made for each flu season in each hemisphere would stabilize the supply, avoid errors in predicting the season's variants, and protect against the escape of the circulating strains by mutation. Such a vaccine has been the subject of research for decades.{{cite journal | vauthors = Cho A, Wrammert J | title = Implications of broadly neutralizing antibodies in the development of a universal influenza vaccine | journal = Current Opinion in Virology | volume = 17 | pages = 110–115 | date = April 2016 | pmid = 27031684 | pmc = 4940123 | doi = 10.1016/j.coviro.2016.03.002 }}

One approach is to use broadly neutralizing antibodies that, unlike the annual seasonal vaccines used over the first decades of the 21st century that provoke the body to generate an immune response, instead provide a component of the immune response itself. The first neutralizing antibodies were identified in 1993, via experimentation.{{cite journal | vauthors = Okuno Y, Isegawa Y, Sasao F, Ueda S | title = A common neutralizing epitope conserved between the hemagglutinins of influenza A virus H1 and H2 strains | journal = Journal of Virology | volume = 67 | issue = 5 | pages = 2552–2558 | date = May 1993 | pmid = 7682624 | pmc = 237575 | doi = 10.1128/JVI.67.5.2552-2558.1993 }} It was found that the flu neutralizing antibodies bound to the stalk of the Hemagglutinin protein. Antibodies that could bind to the head of those proteins were identified. The highly conserved M2 proton channel was proposed as a potential target for broadly neutralizing antibodies.{{cite journal | vauthors = Soema PC, Kompier R, Amorij JP, Kersten GF | title = Current and next generation influenza vaccines: Formulation and production strategies | journal = European Journal of Pharmaceutics and Biopharmaceutics | volume = 94 | pages = 251–263 | date = August 2015 | pmid = 26047796 | doi = 10.1016/j.ejpb.2015.05.023 | doi-access = free | title-link = doi | hdl = 1887/43765 | hdl-access = free }}

The challenges for researchers are to identify single antibodies that could neutralize many subtypes of the virus so that they could be useful in any season, and that target conserved domains that are resistant to antigenic drift.

Another approach is to take the conserved domains identified from these projects, and to deliver groups of these antigens to provoke an immune response; various approaches with different antigens, presented in different ways (as fusion proteins, mounted on virus-like particles, on non-pathogenic viruses, as DNA, and others), are under development.{{cite journal | vauthors = Deng L, Cho KJ, Fiers W, Saelens X | title = M2e-Based Universal Influenza A Vaccines | journal = Vaccines | volume = 3 | issue = 1 | pages = 105–36 | date = February 2015 | pmid = 26344949 | pmc = 4494237 | doi = 10.3390/vaccines3010105 | doi-access = free | title-link = doi }}{{cite journal | vauthors = Gottlieb T, Ben-Yedidia T | title = Epitope-based approaches to a universal influenza vaccine | journal = Journal of Autoimmunity | volume = 54 | pages = 15–20 | date = November 2014 | pmid = 25172355 | doi = 10.1016/j.jaut.2014.07.005 }}

Efforts have also been undertaken to develop universal vaccines that specifically activate a T-cell response, based on clinical data showing that people with a strong, early T-cell response have better outcomes when infected with influenza and because T-cells respond to conserved epitopes. The challenge for developers is that these epitopes are on internal protein domains that are only mildly immunogenic.

Along with the rest of the vaccine field, people working on universal vaccines have experimented with vaccine adjuvants to improve the ability of their vaccines to create a sufficiently powerful and enduring immune response.{{cite journal | vauthors = Toussi DN, Massari P | title = Immune Adjuvant Effect of Molecularly-defined Toll-Like Receptor Ligands | journal = Vaccines | volume = 2 | issue = 2 | pages = 323–53 | date = April 2014 | pmid = 26344622 | pmc = 4494261 | doi = 10.3390/vaccines2020323 | doi-access = free | title-link = doi }}

As of 2019, an oral flu vaccine was in clinical research.{{cite web|url=https://www.drugtopics.com/vaccination-and-immunization/researchers-exploring-oral-flu-vaccine-and-treatment-options|vauthors=Sederstrom J|title=Researchers Exploring Oral Flu Vaccine and Treatment Options|work=Drug Topics |date=July 19, 2019|access-date=January 27, 2020|archive-date=June 8, 2020|archive-url=https://web.archive.org/web/20200608032923/https://www.drugtopics.com/vaccination-and-immunization/researchers-exploring-oral-flu-vaccine-and-treatment-options|url-status=live}} The oral vaccine candidate is based on an adenovirus type{{spaces}}5 vector modified to remove genes needed for replication, with an added gene that expresses a small double-stranded RNA hairpin molecule as an adjuvant.{{cite journal | vauthors = Jasty M, Bragdon CR, Schutzer S, Rubash H, Haire T, Harris WH | title = Bone ingrowth into porous coated canine total hip replacements. Quantification by backscattered scanning electron microscopy and image analysis | journal = Scanning Microscopy | volume = 3 | issue = 4 | pages = 1051–6; discussion 1056–57 | date = December 1989 | pmid = 2633331 | doi = 10.1016/s1473-3099(15)00252-2 }} In 2020, a phase{{spaces}}II human trial of the pill form of the vaccine showed that it was well tolerated and provided similar immunity to a licensed injectable vaccine.{{cite journal | vauthors = Liebowitz D, Gottlieb K, Kolhatkar NS, Garg SJ, Asher JM, Nazareno J, Kim K, McIlwain DR, Tucker SN | title = Efficacy, immunogenicity, and safety of an oral influenza vaccine: a placebo-controlled and active-controlled phase 2 human challenge study | journal = The Lancet. Infectious Diseases | volume = 20 | issue = 4 | pages = 435–444 | date = April 2020 | pmid = 31978354 | doi = 10.1016/S1473-3099(19)30584-5 | publisher = Elsevier | s2cid = 210892802 }}

Recent observational studies and clinical trials suggest nonspecific effects of influenza vaccination, known as pleiotropic effects, with broader impact beyond protecting against influenza infection. A meta-analysis of 9001 randomized trial participants found that influenza vaccination was associated with a 34% lower risk of major adverse cardiovasular events when compared to placebo.{{Cite journal | vauthors = Behrouzi B, Bhatt DL, Cannon CP, Vardeny O, Lee DS, Solomon SD, Udell JA|date=Apr 29, 2022 |title=Association of Influenza Vaccination With Cardiovascular Risk: A Meta-analysis |journal=JAMA Network Open |volume=5 |issue=4 |pages=e228873 |doi=10.1001/jamanetworkopen.2022.8873|pmid=35486404 |pmc=9055450 }} This risk reduction size is comparable to the cardioprotective effects seen with other guideline-recommended cardiovascular medications, including statins.{{Cite journal | vauthors = Behrouzi B, Udell JA|date=Jan 13, 2022 |title=Universal flu vaccines: a shot at lifelong cardioprotection? |journal=Nature Reviews Cardiology |volume=19 |issue=3 |pages=145–146 |doi=10.1038/s41569-021-00670-w |pmid=35027698 |pmc=8757624 }} Protection against stroke of all etiologies has also been suggested in a large population-based retrospective cohort study of 4 million adults in Canada.{{Cite journal | vauthors = Holodinsky JK, Zerna C, Malo S, Svenson LW, Hill MD |date=Nov 30, 2022 |title=Association between influenza vaccination and risk of stroke in Alberta, Canada: a population-based study |journal=Lancet Public Health |volume=7 |issue=11 |pages=e914–e922|doi=10.1016/S2468-2667(22)00222-5|pmid=36334607 |doi-access=free }} There may also be protective effects against the development of type 1 diabetes and cancer-related mortality, which are active areas of investigation.{{Cite journal | vauthors = Hjelholt AJ, Bergh C, Bhatt DL, Frobert O, Kjolby MF |date=Aug 25, 2023 |title=Pleiotropic Effects of Influenza Vaccination |journal=Vaccines |volume=11 |issue=9 |pages=1419 |doi=10.3390/vaccines11091419|doi-access=free |pmid=37766096 |pmc=10536538 }}

An influenza vaccine and a COVID-19 vaccine may be given safely at the same time.{{cite web | title=Flu vaccine | publisher=UK National Health Service | date=May 13, 2022 | url=https://www.nhs.uk/conditions/vaccinations/flu-influenza-vaccine/ | access-date=August 13, 2022 | archive-date=October 26, 2021 | archive-url=https://web.archive.org/web/20211026210525/https://www.nhs.uk/conditions/vaccinations/flu-influenza-vaccine/ | url-status=live }}{{cite web | vauthors = Triggle N | title=Flu jab vital this winter along with Covid vaccine | website=BBC News | date=October 8, 2021 | url=https://www.bbc.com/news/health-58836218 | access-date=August 13, 2022 | archive-date=November 14, 2021 | archive-url=https://web.archive.org/web/20211114150601/https://www.bbc.com/news/health-58836218 | url-status=live }} Preliminary research indicates that influenza vaccination does not prevent COVID-19, but may reduce the incidence and severity of COVID-19 infection.{{Cite journal | vauthors = Callaway E |date=May 16, 2022 |title=Flu vaccine could cut COVID risk |journal=Nature |volume=605 |issue=7911 |pages=602 |doi=10.1038/d41586-022-01315-9|pmid=35581411 |bibcode=2022Natur.605..602C |s2cid=248859545 |doi-access=free }}

Tom Jefferson, who has led Cochrane Collaboration reviews of flu vaccines, has called clinical evidence concerning flu vaccines "rubbish" and has therefore declared them to be ineffective; he has called for placebo-controlled randomized clinical trials, which most in the field hold as unethical. His views on the efficacy of flu vaccines are rejected by medical institutions including the CDC and the National Institutes of Health, and by key figures in the field like Anthony Fauci.{{cite web | url=https://www.theatlantic.com/magazine/archive/2009/11/does-the-vaccine-matter/307723/ | title=Does the Vaccine Matter? | work=The Atlantic | date=November 1, 2009 | access-date=December 8, 2014 | vauthors = Brownlee S | url-status=live | archive-url=https://web.archive.org/web/20141209000238/http://www.theatlantic.com/magazine/archive/2009/11/does-the-vaccine-matter/307723/ | archive-date=December 9, 2014 }}

Michael Osterholm, who led the Center for Infectious Disease Research and Policy 2012 review on flu vaccines, recommended getting the vaccine but criticized its promotion, saying, "We have overpromoted and overhyped this vaccine{{spaces}}... it does not protect as promoted. It's all a sales job: it's all public relations."{{cite news| vauthors = Rabin RC |title=Reassessing Flu Shots as the Season Draws Near|url=http://well.blogs.nytimes.com/2012/11/05/reassessing-flu-shots-as-the-season-draws-near/|date=November 5, 2012|access-date=December 30, 2016|work=The New York Times|url-status=live|archive-url= https://web.archive.org/web/20161110060218/http://well.blogs.nytimes.com/2012/11/05/reassessing-flu-shots-as-the-season-draws-near/|archive-date=November 10, 2016|quote='We have overpromoted and overhyped this vaccine,' said Michael T. Osterholm, director of the Center for Infectious Disease Research and Policy, as well as its Center of Excellence for Influenza Research and Surveillance. 'It does not protect as promoted. It's all a sales job: it's all public relations.'}}

{{See also|Influenza A virus|Influenza#Infection in other animals}}

Veterinary influenza vaccination aims to achieve the following four objectives:[http://www.influenzareport.com/ir/ai.htm Influenza Report (online book)] {{webarchive|url=https://web.archive.org/web/20160510091835/http://www.influenzareport.com/ir/ai.htm|date=May 10, 2016}} chapter Avian Influenza by Timm C. Harder and Ortrud Werner

1. Protection from clinical disease
2. Protection from infection with virulent virus
3. Protection from virus excretion
4. Serological differentiation of infected from vaccinated animals (so-called DIVA principle).

Horses with horse flu can run a fever, have a dry hacking cough, have a runny nose, and become depressed and reluctant to eat or drink for several days but usually recover in two to three weeks. "Vaccination schedules generally require a primary course of two doses, 3–6 weeks apart, followed by boosters at 6–12 month intervals. It is generally recognized that in many cases such schedules may not maintain protective levels of antibody and more frequent administration is advised in high-risk situations."[http://195.224.162.216/equiflunet/equiflunet_vaccines.html equiflunet_vaccines] {{webarchive|url=https://web.archive.org/web/20060110083319/http://195.224.162.216/equiflunet/equiflunet_vaccines.html |date=January 10, 2006 }}

It is a common requirement at shows in the United Kingdom that horses be vaccinated against equine flu and a vaccination card must be produced; the International Federation for Equestrian Sports (FEI) requires vaccination every six months.{{cite web|url=http://www.uaeequafed.ae/veterinary.htm|archive-url=https://web.archive.org/web/20050322085433/http://www.uaeequafed.ae/veterinary.htm|archive-date=March 22, 2005|title=UAE Equestrian & Racing Federation|date=March 22, 2005}}{{cite web|url=http://www.horsesport.org/veterinary/PDFS/InflVaccGuide-E.pdf|title=FEI guidelines|url-status=live|archive-url=https://web.archive.org/web/20071026124033/http://www.horsesport.org/veterinary/PDFS/InflVaccGuide-E.pdf|archive-date=October 26, 2007}}

It is possible to vaccinate poultry against specific strains of highly pathogenic avian influenza. Vaccination should be combined with other control measures such as infection monitoring, early detection, and biosecurity.{{Cite web |date=October 10, 2023 |title=Vaccination of poultry against highly pathogenic avian influenza – Available vaccines and vaccination strategies |url=https://www.efsa.europa.eu/en/news/vaccination-poultry-against-highly-pathogenic-avian-influenza-available-vaccines-and |access-date=May 9, 2024 |website=efsa.europa.eu }}{{Cite web |date=June 3, 2024 |title=Making a Candidate Vaccine Virus (CVV) for a HPAI (Bird Flu) Virus |url=https://www.cdc.gov/bird-flu/php/severe-potential/candidate-vaccine-virus.html |access-date=June 15, 2024 |work=U.S. Centers for Disease Control and Prevention (CDC) }}

Swine influenza vaccines are extensively used in pig farming in Europe and North America. Most swine flu vaccines include an H1N1 and an H3N2 strain.

Swine influenza has been recognized as a major problem since the outbreak in 1976. Evolution of the virus has resulted in inconsistent responses to traditional vaccines. Standard commercial swine flu vaccines are effective in controlling the problem when the virus strains match enough to have significant cross-protection. Customised (autogenous) vaccines made from the specific viruses isolated are made and used in the more difficult cases.{{cite web |url=http://nationalhogfarmer.com/mag/swine_flu_virus_endemic/ |title=Swine Flu Virus Turns Endemic |date=September 15, 2007 |archive-url=https://web.archive.org/web/20090429090534/http://nationalhogfarmer.com/mag/swine_flu_virus_endemic/ |archive-date=April 29, 2009 }} The vaccine manufacturer Novartis claims that the H3N2 strain (first identified in 1998) has brought major losses to pig farmers. Abortion storms are a common sign and sows stop eating for a few days and run a high fever. The mortality rate can be as high as fifteen percent.{{cite web |url=http://www.livestock.novartis.com/cv_swine.html |title=Custom Vaccines: Swine |archive-url=https://web.archive.org/web/20090430094251/http://www.livestock.novartis.com/cv_swine.html |archive-date=April 30, 2009 }}

In 2004, influenza A virus subtype H3N8 was discovered to cause canine influenza. Because of the lack of previous exposure to this virus, dogs have no natural immunity to this virus. However, a vaccine was found in 2004.{{cite journal | vauthors = Karaca K, Dubovi EJ, Siger L, Robles A, Audonnet JC, Jiansheng Y, Nordgren R, Minke JM | title = Evaluation of the ability of canarypox-vectored equine influenza virus vaccines to induce humoral immune responses against canine influenza viruses in dogs | journal = American Journal of Veterinary Research | volume = 68 | issue = 2 | pages = 208–12 | date = February 2007 | pmid = 17269888 | doi = 10.2460/ajvr.68.2.208 }}

{{Reflist|group="note"}}

{{Reflist}}

{{refbegin}}

• {{cite book | title=The immunological basis for immunization series: module 23: influenza vaccines | publisher=World Health Organization (WHO) | date=October 2017 | hdl=10665/259211 | isbn=978-92-4-151305-0 | hdl-access=free }}
• {{cite book | title=Immunisation against infectious disease | chapter=Chapter 19: Influenza | date=January 21, 2021 | chapter-url=https://www.gov.uk/government/publications/influenza-the-green-book-chapter-19 | publisher=Public Health England | veditors=Ramsay M | url=https://www.gov.uk/government/collections/immunisation-against-infectious-disease-the-green-book | access-date=October 24, 2019 | archive-date=November 12, 2019 | archive-url=https://web.archive.org/web/20191112005859/https://www.gov.uk/government/publications/pneumococcal-the-green-book-chapter-25 | url-status=live }}
• {{cite book | publisher = U.S. Centers for Disease Control and Prevention (CDC) | title = Epidemiology and Prevention of Vaccine-Preventable Diseases | veditors = Hall E, Wodi AP, Hamborsky J, Morelli V, Schillie S | edition = 14th | location = Washington D.C. | year = 2021 | chapter = Chapter 12: Influenza | chapter-url = https://www.cdc.gov/vaccines/pubs/pinkbook/flu.html | url = https://www.cdc.gov/vaccines/pubs/pinkbook/index.html | access-date = October 24, 2019 | archive-date = December 30, 2016 | archive-url = https://web.archive.org/web/20161230001534/https://www.cdc.gov/vaccines/pubs/pinkbook/index.html | url-status = live }}
• {{cite book | vauthors = Budd A, Blanton L, Grohskopf L, Campbell A, Dugan V, Wentworth DE, Brammer L | chapter = Chapter 6: Influenza | chapter-url = https://www.cdc.gov/vaccines/pubs/surv-manual/chpt06-influenza.html | veditors = Roush SW, Baldy LM, Hall MA | title = Manual for the surveillance of vaccine-preventable diseases | publisher = U.S. Centers for Disease Control and Prevention (CDC) | location = Atlanta GA | url = https://www.cdc.gov/vaccines/pubs/surv-manual/ | date = March 29, 2019 | access-date = October 24, 2019 | archive-date = August 1, 2020 | archive-url = https://web.archive.org/web/20200801192220/https://www.cdc.gov/vaccines/pubs/surv-manual/ | url-status = live }}
• {{cite web | author=National Advisory Committee on Immunization | title=Canadian Immunization Guide Chapter on Influenza and Statement on Seasonal Influenza Vaccine for 2020–2021 | website=Public Health Agency of Canada | date=May 2020 | url=https://www.canada.ca/content/dam/phac-aspc/documents/services/publications/healthy-living/canadian-immunization-guide-statement-seasonal-influenza-vaccine-2020-2021/naci-2020-2021-seasonal-influenza-stmt-eng.pdf | id=Cat.: HP37-25F-PDF; Pub.: 200003 | access-date=June 2, 2020 | archive-date=August 3, 2020 | archive-url=https://web.archive.org/web/20200803062906/https://www.canada.ca/content/dam/phac-aspc/documents/services/publications/healthy-living/canadian-immunization-guide-statement-seasonal-influenza-vaccine-2020-2021/naci-2020-2021-seasonal-influenza-stmt-eng.pdf | url-status=live }}
• {{lay source |template=cite magazine |vauthors=Young K, Gemmill I, Harrison R |collaboration=National Advisory Committee on Immunization |date=May 7, 2020 |title=Summary of the NACI Seasonal Influenza Vaccine Statement for 2020–2021 |periodical=Canada Communicable Disease Report |volume=46 |issue=5 |url=https://www.canada.ca/en/public-health/services/reports-publications/canada-communicable-disease-report-ccdr/monthly-issue/2020-46/issue-5-may-7-2020/naci-summary-influenza-2020-2021.html}}
• {{cite book | author=National Advisory Committee on Immunization (NACI) | title=NACI literature review on the comparative effectiveness and immunogenicity of subunit and split virus inactivated influenza vaccines in adults 65 years of age and older | id=Cat.: HP40-213/2018E-PDF; Pub.: 180039 | publisher=Government of Canada | date=May 2018 | url=http://publications.gc.ca/collections/collection_2018/aspc-phac/HP40-213-2018-eng.pdf | isbn=978-0-660-26438-7 | access-date=January 12, 2020 | archive-date=July 18, 2020 | archive-url=https://web.archive.org/web/20200718004211/http://publications.gc.ca/collections/collection_2018/aspc-phac/HP40-213-2018-eng.pdf | url-status=live }}
• {{lay source |template=cite magazine |vauthors=Gemmill I, Young K |collaboration=National Advisory Committee on Immunization |date=June 7, 2018 |title=Summary of the NACI literature review on the comparative effectiveness of subunit and split virus inactivated influenza vaccines in older adults |periodical=Canada Communicable Disease Report |volume=44 |issue=6 |url=https://www.canada.ca/en/public-health/services/reports-publications/canada-communicable-disease-report-ccdr/monthly-issue/2018-44/issue-6-june-7-2018/article-2-summary-subunit-split-virus-influenza-vaccine.html}}
• {{cite journal |vauthors=Rajaram S, Wojcik R, Moore C, Ortiz de Lejarazu R, de Lusignan S, Montomoli E, Rossi A, Pérez-Rubio A, Trilla A, Baldo V, Jandhyala R, Kassianos G |title=The impact of candidate influenza virus and egg-based manufacture on vaccine effectiveness: Literature review and expert consensus |journal=Vaccine |volume=38 |issue=38 |pages=6047–6056 |date=August 2020 |pmid=32600916 |doi=10.1016/j.vaccine.2020.06.021 | doi-access = free | title-link = doi }}

{{refend}}

{{Wikiquote}}

• [https://www.cdc.gov/vaccines/hcp/vis/vis-statements/flu.html Inactivated Influenza Vaccine Information Statement], US Centers for Disease Control and Prevention (CDC)
• [https://www.cdc.gov/vaccines/hcp/vis/vis-statements/flulive.html Live, Intranasal Influenza Vaccine Information Statement], US Centers for Disease Control and Prevention (CDC)
• [https://www.cdc.gov/vaccines/vpd-vac/flu/default.htm Seasonal Influenza (Flu) Vaccination and Preventable Disease], US Centers for Disease Control and Prevention (CDC)
• [https://www.cdc.gov/flu/prevent/misconceptions.htm Misconceptions about Seasonal Flu and Flu Vaccines], US Centers for Disease Control and Prevention (CDC)
• {{MeshName|Influenza Vaccines}}

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Category:Live vaccines

Category:World Health Organization essential medicines (vaccines)

Category:Wikipedia medicine articles ready to translate

Category:Inactivated vaccines