Attenuated vaccine

Viruses may be attenuated using the principles of evolution with serial passage of the virus through a foreign host species, such as:{{Cite journal|last1=Jordan|first1=Ingo|last2=Sandig|first2=Volker|date=2014-04-11|title=Matrix and Backstage: Cellular Substrates for Viral Vaccines|journal=Viruses|volume=6|issue=4|pages=1672–1700|doi=10.3390/v6041672|issn=1999-4915|pmc=4014716|pmid=24732259|doi-access=free}}{{Cite book|date=2015|editor-last=Nunnally|editor-first=Brian K.|editor2-last=Turula|editor2-first=Vincent E.|editor3-last=Sitrin|editor3-first=Robert D.|title=Vaccine Analysis: Strategies, Principles, and Control|url=https://link.springer.com/book/10.1007/978-3-662-45024-6|language=en-gb|doi=10.1007/978-3-662-45024-6|isbn=978-3-662-45023-9|s2cid=39542692|access-date=3 November 2020|archive-date=25 January 2023|archive-url=https://web.archive.org/web/20230125193900/https://link.springer.com/book/10.1007/978-3-662-45024-6|url-status=live}}

• Tissue culture
• Embryonated eggs (often chicken)
• Live animals

The initial virus population is applied to a foreign host. Through natural genetic variability or induced mutation, a small percentage of the viral particles should have the capacity to infect the new host.{{Cite journal|last=Hanley|first=Kathryn A.|date=December 2011|title=The double-edged sword: How evolution can make or break a live-attenuated virus vaccine|journal=Evolution|volume=4|issue=4|pages=635–643|doi=10.1007/s12052-011-0365-y|issn=1936-6426|pmc=3314307|pmid=22468165}} These strains will continue to evolve within the new host and the virus will gradually lose its efficacy in the original host, due to lack of selection pressure. This process is known as "passage" in which the virus becomes so well adapted to the foreign host that it is no longer harmful to the subject that is to receive the vaccine. This makes it easier for the host immune system to eliminate the agent and create the immunological memory cells which will likely protect the patient if they are infected with a similar version of the virus in "the wild".

Viruses may also be attenuated via reverse genetics.{{Cite journal|last1=Nogales|first1=Aitor|last2=Martínez-Sobrido|first2=Luis|date=2016-12-22|title=Reverse Genetics Approaches for the Development of Influenza Vaccines|journal=International Journal of Molecular Sciences|volume=18|issue=1|page=20|doi=10.3390/ijms18010020|issn=1422-0067|pmc=5297655|pmid=28025504|doi-access=free}} Attenuation by genetics is also used in the production of oncolytic viruses.{{cite journal |vauthors= Gentry GA |title= Viral thymidine kinases and their relatives |journal= Pharmacology & Therapeutics |volume= 54 |issue= 3 |pages= 319–55 |year= 1992 |pmid= 1334563 |doi= 10.1016/0163-7258(92)90006-L}}

Bacteria is typically attenuated by passage, similar to the method used in viruses.{{cite web |title=Immunology and Vaccine-Preventable Diseases |url=https://www.cdc.gov/vaccines/pubs/pinkbook/downloads/prinvac.pdf |website=CDC |access-date=9 December 2020 |archive-date=8 April 2020 |archive-url=https://web.archive.org/web/20200408173837/https://www.cdc.gov/vaccines/pubs/pinkbook/downloads/prinvac.pdf |url-status=live }} Gene knockout guided by reverse genetics is also used.{{cite journal |last1=Xiong |first1=Kun |last2=Zhu |first2=Chunyue |last3=Chen |first3=Zhijin |last4=Zheng |first4=Chunping |last5=Tan |first5=Yong |last6=Rao |first6=Xiancai |last7=Cong |first7=Yanguang |title=Vi Capsular Polysaccharide Produced by Recombinant Salmonella enterica Serovar Paratyphi A Confers Immunoprotection against Infection by Salmonella enterica Serovar Typhi |journal=Frontiers in Cellular and Infection Microbiology |date=24 April 2017 |volume=7 |pages=135 |doi=10.3389/fcimb.2017.00135|pmid=28484685 |pmc=5401900 |doi-access=free }}

Attenuated vaccines can be administered in a variety of ways:

• Injections:
• Subcutaneous (e.g. measles, mumps and rubella vaccine, varicella vaccine, yellow fever vaccine){{Cite journal|last=Herzog|first=Christian|date=2014|title=Influence of parenteral administration routes and additional factors on vaccine safety and immunogenicity: a review of recent literature|url=http://www.tandfonline.com/doi/full/10.1586/14760584.2014.883285|journal=Expert Review of Vaccines|language=en|volume=13|issue=3|pages=399–415|doi=10.1586/14760584.2014.883285|pmid=24512188|s2cid=46577849|issn=1476-0584|access-date=16 November 2020|archive-date=25 January 2023|archive-url=https://web.archive.org/web/20230125193859/https://www.tandfonline.com/doi/full/10.1586/14760584.2014.883285|url-status=live|url-access=subscription}}
• Intradermal (e.g. tuberculosis vaccine, smallpox vaccine)
• Mucosal:
• Nasal (e.g. live attenuated influenza vaccine){{Cite journal|last1=Gasparini|first1=R.|last2=Amicizia|first2=D.|last3=Lai|first3=P. L.|last4=Panatto|first4=D.|date=2011|title=Live attenuated influenza vaccine--a review|url=https://pubmed.ncbi.nlm.nih.gov/22010534|journal=Journal of Preventive Medicine and Hygiene|volume=52|issue=3|pages=95–101|issn=1121-2233|pmid=22010534|access-date=16 November 2020|archive-date=25 January 2023|archive-url=https://web.archive.org/web/20230125193859/https://pubmed.ncbi.nlm.nih.gov/22010534/|url-status=live}}
• Oral (e.g. oral polio vaccine, recombinant live attenuated cholera vaccine, oral typhoid vaccine, oral rotavirus vaccine){{Cite book|last=Morrow, W. John W.|url=https://www.worldcat.org/oclc/795120561|title=Vaccinology : Principles and Practice.|date=2012|publisher=John Wiley & Sons|others=Sheikh, Nadeem A., Schmidt, Clint S., Davies, D. Huw.|isbn=978-1-118-34533-7|location=Hoboken|oclc=795120561}}

Oral vaccines or subcutaneous/intramuscular injection are for individuals older than 12 months. Live attenuated vaccines, with the exception of the rotavirus vaccine given at 6 weeks, is not indicated for infants younger than 9 months.{{Cite web |title=Your Child's Immunizations: Rotavirus Vaccine (RV) (for Parents) - Nemours KidsHealth |url=https://kidshealth.org/en/parents/rotavirus-vaccine.html |access-date=2022-09-15 |website=kidshealth.org |archive-date=25 January 2023 |archive-url=https://web.archive.org/web/20230125193900/https://kidshealth.org/en/parents/rotavirus-vaccine.html |url-status=live }}

Vaccines function by encouraging the creation of immune cells, such as CD8+ and CD4+ T lymphocytes, or molecules, such as antibodies, that are specific to the pathogen.{{Cite book|url=https://www.worldcat.org/oclc/989157433|title=Plotkin's vaccines|others=Plotkin, Stanley A., 1932-, Orenstein, Walter A.,, Offit, Paul A.|year=2018|isbn=978-0-323-39302-7|edition=Seventh|location=Philadelphia, PA|oclc=989157433}} The cells and molecules can either prevent or reduce infection by killing infected cells or by producing interleukins. The specific effectors evoked can be different based on the vaccine. Live attenuated vaccines tend to help with the production of CD8+ cytotoxic T lymphocytes and T-dependent antibody responses. A vaccine is only effective for as long as the body maintains a population of these cells.

Attenuated vaccines are “weakened” versions of pathogens (virus or bacteria). They are modified so that it cannot cause harm or disease in the body but are still able to activate the immune system.{{Cite web |date=2021-04-26 |title=Vaccine Types |url=https://www.hhs.gov/immunization/basics/types/index.html |url-status=live |archive-url=https://web.archive.org/web/20210716125750/https://www.hhs.gov/immunization/basics/types/index.html |archive-date=16 July 2021 |access-date=2022-09-15 |website=HHS.gov |language=en}} This type of vaccine works by activating both the cellular and humoral immune responses of the adaptive immune system. When a person receives an oral or injection of the vaccine, B cells, which help make antibodies, are activated in two ways: T cell-dependent and T-cell independent activation.{{Cite book |last=Sompayrac |first=Lauren |url=https://www.worldcat.org/oclc/1083261548 |title=How the immune system works |date=2019 |isbn=978-1-119-54212-4 |edition=Sixth |location=Hoboken, NJ |oclc=1083261548}}

In T-cell dependent activation of B cells, B cells first recognize and present the antigen on MHCII receptors. T-cells can then recognize this presentation and bind to the B cell, resulting in clonal proliferation. This also helps IgM and plasma cells production as well as immunoglobulin switching. On the other hand, T-cell independent activation of B cells is due to non-protein antigens. This can lead to production of IgM antibodies. Being able to produce a B-cell response as well as memory killer T cells is a key feature of attenuated virus vaccines that help induce a potent immunity.

Live-attenuated vaccines are safe and stimulate a strong and effective immune response that is long-lasting. Given that pathogens are attenuated, it is extremely rare for pathogens to revert to their pathogenic form and subsequently cause disease.{{Cite web|title=MODULE 2 – Live attenuated vaccines (LAV) - WHO Vaccine Safety Basics|url=https://vaccine-safety-training.org/live-attenuated-vaccines.html|access-date=2020-11-16|website=vaccine-safety-training.org|archive-date=12 November 2020|archive-url=https://web.archive.org/web/20201112032856/https://vaccine-safety-training.org/live-attenuated-vaccines.html|url-status=live}} Additionally, amongst the five WHO-recommended live attenuated vaccines (tuberculosis, oral polio, measles, rotavirus, and yellow fever), severe adverse reactions are extremely rare.

Individuals with severely compromised immune systems (e.g., HIV-infection, chemotherapy, immunosuppressive therapy, lymphoma, leukemia, combined immunodeficiencies) typically should not receive live-attenuated vaccines as they may not be able to produce an adequate and safe immune response.{{Citation|last1=Yadav|first1=Dinesh K.|title=Chapter 26 - Vaccines: Present Status and Applications|date=2014-01-01|url=http://www.sciencedirect.com/science/article/pii/B9780124160026000262|work=Animal Biotechnology|pages=491–508|editor-last=Verma|editor-first=Ashish S.|place=San Diego|publisher=Academic Press|language=en|doi=10.1016/b978-0-12-416002-6.00026-2|isbn=978-0-12-416002-6|access-date=2020-11-16|last2=Yadav|first2=Neelam|last3=Khurana|first3=Satyendra Mohan Paul|s2cid=83112999 |editor2-last=Singh|editor2-first=Anchal|url-access=subscription}}{{Cite journal|last1=Sobh|first1=Ali|last2=Bonilla|first2=Francisco A.|date=Nov 2016|title=Vaccination in Primary Immunodeficiency Disorders|url=https://linkinghub.elsevier.com/retrieve/pii/S2213219816304081|journal=The Journal of Allergy and Clinical Immunology: In Practice|language=en|volume=4|issue=6|pages=1066–1075|doi=10.1016/j.jaip.2016.09.012|pmid=27836056|access-date=17 November 2020|archive-date=25 January 2023|archive-url=https://web.archive.org/web/20230125193907/https://www.jaci-inpractice.org/article/S2213-2198(16)30408-1/fulltext|url-status=live|url-access=subscription}} Household contacts of immunodeficient individuals are still able to receive most attenuated vaccines since there is no increased risk of infection transmission, with the exception being the oral polio vaccine.

As a precaution, live-attenuated vaccines are not typically administered during pregnancy.{{Citation|last1=Su|first1=John R.|title=Vaccine Safety|date=2019|url=https://linkinghub.elsevier.com/retrieve/pii/B978032355435000001X|work=Vaccinations|pages=1–24|publisher=Elsevier|language=en|doi=10.1016/b978-0-323-55435-0.00001-x|isbn=978-0-323-55435-0|access-date=2020-11-17|last2=Duffy|first2=Jonathan|last3=Shimabukuro|first3=Tom T.|s2cid=239378645|archive-date=25 January 2023|archive-url=https://web.archive.org/web/20230125173506/https://www.sciencedirect.com/science/article/pii/B978032355435000001X?via%3Dihub|url-status=live|url-access=subscription}} This is due to the risk of transmission of virus between mother and fetus. In particular, the varicella and yellow fever vaccines have been shown to have adverse effects on fetuses and nursing babies.

Some live attenuated vaccines have additional common, mild adverse effects due to their administration route. For example, the live attenuated influenza vaccine is given nasally and is associated with nasal congestion.

Compared to inactivated vaccines, live-attenuated vaccines are more prone to immunization errors as they must be kept under strict conditions during the cold chain and carefully prepared (e.g., during reconstitution).

The history of vaccine development started with the creation of the smallpox vaccine by Edward Jenner in the late 18th century.{{Cite journal|last=Plotkin|first=Stanley|date=2014-08-26|title=History of vaccination|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=111|issue=34|pages=12283–12287|doi=10.1073/pnas.1400472111|issn=1091-6490|pmc=4151719|pmid=25136134|bibcode=2014PNAS..11112283P|doi-access=free}} Jenner discovered that inoculating a human with an animal pox virus would grant immunity against smallpox, a disease considered to be one of the most devastating in human history.{{Cite journal|last=Eyler|first=John M.|date=October 2003|title=Smallpox in history: the birth, death, and impact of a dread disease|url=https://doi.org/10.1016/S0022-2143(03)00102-1|journal=Journal of Laboratory and Clinical Medicine|volume=142|issue=4|pages=216–220|doi=10.1016/s0022-2143(03)00102-1|pmid=14625526|issn=0022-2143|access-date=23 November 2020|archive-date=25 January 2023|archive-url=https://web.archive.org/web/20230125173506/https://www.translationalres.com/article/S0022-2143(03)00102-1/fulltext|url-status=live|url-access=subscription}}{{Citation|last1=Thèves|first1=Catherine|title=History of Smallpox and Its Spread in Human Populations|date=2016-09-15|url=http://www.asmscience.org/content/book/10.1128/9781555819170.chap16|work=Paleomicrobiology of Humans|pages=161–172|editor-last=Drancourt|publisher=American Society of Microbiology|language=en|doi=10.1128/microbiolspec.poh-0004-2014|isbn=978-1-55581-916-3|access-date=2020-11-14|last2=Crubézy|first2=Eric|last3=Biagini|first3=Philippe|volume=4|issue=4|pmid=27726788|editor2-last=Raoult|archive-date=25 January 2023|archive-url=https://web.archive.org/web/20230125193904/https://asm.org/a/ASMScience|url-status=live|url-access=subscription}} Although the original smallpox vaccine is sometimes considered to be an attenuated vaccine due to its live nature, it was not strictly-speaking attenuated since it was not derived directly from smallpox. Instead, it was based on the related and milder cowpox disease.{{Citation|last1=Galinski|first1=Mark S.|title=Live Attenuated Viral Vaccines|date=2015|url=https://doi.org/10.1007/978-3-662-45024-6_1|work=Vaccine Analysis: Strategies, Principles, and Control|pages=1–44|editor-last=Nunnally|editor-first=Brian K.|place=Berlin, Heidelberg|publisher=Springer|language=en|doi=10.1007/978-3-662-45024-6_1|isbn=978-3-662-45024-6|access-date=2020-11-14|last2=Sra|first2=Kuldip|last3=Haynes|first3=John I.|last4=Naspinski|first4=Jennifer|editor2-last=Turula|editor2-first=Vincent E.|editor3-last=Sitrin|editor3-first=Robert D.|archive-date=25 January 2023|archive-url=https://web.archive.org/web/20230125173510/https://link.springer.com/chapter/10.1007/978-3-662-45024-6_1|url-status=live|url-access=subscription}}{{Cite journal|date=2015-05-01|title=Live attenuated vaccines: Historical successes and current challenges|journal=Virology|language=en|volume=479-480|pages=379–392|doi=10.1016/j.virol.2015.03.032|issn=0042-6822|last1=Minor|first1=Philip D.|pmid=25864107|doi-access=free}} The discovery that diseases could be artificially attenuated came in the late 19th century when Louis Pasteur was able to derive an attenuated strain of chicken cholera. Pasteur applied this knowledge to develop an attenuated anthrax vaccine and demonstrating its effectiveness in a public experiment.{{Cite journal|last=Schwartz|first=M.|date=7 July 2008|title=The life and works of Louis Pasteur|journal=Journal of Applied Microbiology|volume=91|issue=4|pages=597–601|doi=10.1046/j.1365-2672.2001.01495.x|issn=1364-5072|pmid=11576293|s2cid=39020116|doi-access=}} The first rabies vaccine was subsequently produced by Pasteur and Emile Roux by growing the virus in rabbits and drying the affected nervous tissue.

The technique of cultivating a virus repeatedly in artificial media and isolating less virulent strains was pioneered in the early 20th century by Albert Calmette and Camille Guérin who developed an attenuated tuberculosis vaccine called the BCG vaccine. This technique was later used by several teams when developing the vaccine for yellow fever, first by Sellards and Laigret, and then by Theiler and Smith.{{Cite journal|last=Frierson|first=J. Gordon|date=June 2010|title=The Yellow Fever Vaccine: A History|journal=The Yale Journal of Biology and Medicine|volume=83|issue=2|pages=77–85|issn=0044-0086|pmc=2892770|pmid=20589188}} The vaccine developed by Theiler and Smith proved to be hugely successful and helped establish recommended practices and regulations for many other vaccines. These include the growth of viruses in primary tissue culture (e.g., chick embryos), as opposed to animals, and the use of the seed stock system which uses the original attenuated viruses as opposed to derived viruses (done to reduce variance in vaccine development and decrease the chance of adverse effects). The middle of the 20th century saw the work of many prominent virologists including Sabin, Hilleman, and Enders, and the introduction of several successful attenuated vaccines, such as those against polio, measles, mumps, and rubella.{{Cite journal|last1=Shampo|first1=Marc A.|last2=Kyle|first2=Robert A.|last3=Steensma|first3=David P.|date=July 2011|title=Albert Sabin—Conqueror of Poliomyelitis|journal=Mayo Clinic Proceedings|volume=86|issue=7|pages=e44|doi=10.4065/mcp.2011.0345|issn=0025-6196|pmc=3127575|pmid=21719614}}{{Cite journal|last=Newman|first=Laura|date=2005-04-30|title=Maurice Hilleman|journal=BMJ: British Medical Journal|volume=330|issue=7498|pages=1028|doi=10.1136/bmj.330.7498.1028|pmc=557162|issn=0959-8138}}{{Cite book|last=Katz|first=S. L.|title=Measles|chapter=John F. Enders and Measles Virus Vaccine—a Reminiscence|series=Current Topics in Microbiology and Immunology|date=2009|chapter-url=https://pubmed.ncbi.nlm.nih.gov/19198559/|volume=329|pages=3–11|doi=10.1007/978-3-540-70523-9_1|issn=0070-217X|pmid=19198559|isbn=978-3-540-70522-2|s2cid=2884917|access-date=23 November 2020|archive-date=27 January 2021|archive-url=https://web.archive.org/web/20210127194814/https://pubmed.ncbi.nlm.nih.gov/19198559/|url-status=live}}{{Cite journal|last=Plotkin|first=Stanley A.|date=2006-11-01|title=The History of Rubella and Rubella Vaccination Leading to Elimination|journal=Clinical Infectious Diseases|language=en|volume=43|issue=Supplement_3|pages=S164–S168|doi=10.1086/505950|pmid=16998777|issn=1058-4838|doi-access=free}}

• Accurately imitate natural infections.{{Citation|last1=Yadav|first1=Dinesh K.|title=Vaccines|date=2014|url=https://linkinghub.elsevier.com/retrieve/pii/B9780124160026000262|work=Animal Biotechnology|pages=491–508|publisher=Elsevier|language=en|doi=10.1016/b978-0-12-416002-6.00026-2|isbn=978-0-12-416002-6|access-date=2020-11-09|last2=Yadav|first2=Neelam|last3=Khurana|first3=Satyendra Mohan Paul|s2cid=83112999|archive-date=25 January 2023|archive-url=https://web.archive.org/web/20230125193905/https://www.sciencedirect.com/science/article/pii/B9780124160026000262?via%3Dihub|url-status=live|url-access=subscription}}{{Cite journal|last1=Vetter|first1=Volker|last2=Denizer|first2=Gülhan|last3=Friedland|first3=Leonard R.|last4=Krishnan|first4=Jyothsna|last5=Shapiro|first5=Marla|date=2018-02-17|title=Understanding modern-day vaccines: what you need to know|journal=Annals of Medicine|volume=50|issue=2|pages=110–120|doi=10.1080/07853890.2017.1407035|issn=0785-3890|pmid=29172780|s2cid=25514266|doi-access=free}}
• Are effective at evoking both strong antibody and cell-mediated immune reactions.
• Can elicit long-lasting or life-long immunity.
• Often only one or two doses are required.
• Quick immunity onset.
• Cost-effective (compared to some other health interventions).{{Cite journal|last=Minor|first=Philip D.|date=May 2015|title=Live attenuated vaccines: Historical successes and current challenges|journal=Virology|volume=479-480|pages=379–392|doi=10.1016/j.virol.2015.03.032|issn=1096-0341|pmid=25864107|doi-access=free}}{{Citation|last1=Mak|first1=Tak W.|title=23 - Vaccines and Clinical Immunization|date=2006-01-01|url=http://www.sciencedirect.com/science/article/pii/B9780120884513500259|work=The Immune Response|pages=695–749|editor-last=Mak|editor-first=Tak W.|place=Burlington|publisher=Academic Press|language=en|isbn=978-0-12-088451-3|access-date=2020-11-14|last2=Saunders|first2=Mary E.|editor2-last=Saunders|editor2-first=Mary E.}}
• Can have strong beneficial non-specific effects.{{Cite journal|last1=Benn|first1=Christine S.|last2=Netea|first2=Mihai G.|last3=Selin|first3=Liisa K.|last4=Aaby|first4=Peter|date=September 2013|title=A small jab – a big effect: nonspecific immunomodulation by vaccines|journal=Trends in Immunology|volume=34|issue=9|pages=431–439|doi=10.1016/j.it.2013.04.004|pmid=23680130}}

• In rare cases, particularly when there is inadequate vaccination of the population, natural mutations during viral replication, or interference by related viruses, can cause an attenuated virus to revert to its wild-type form or mutate to a new strain, potentially resulting in the new virus being infectious or pathogenic.{{cite journal|display-authors=etal|vauthors=Shimizu H, Thorley B, Paladin FJ|date=December 2004|title=Circulation of type 1 vaccine-derived poliovirus in the Philippines in 2001|journal=J. Virol.|volume=78|issue=24|pages=13512–21|doi=10.1128/JVI.78.24.13512-13521.2004|pmc=533948|pmid=15564462}}
• Often not recommended in pregnancy or for severely immunocompromised patients due to the risk of potential complications.{{cite news|last=Kroger|first=Andrew T.|author2=Ciro V. Sumaya|author3=Larry K. Pickering|author4=William L. Atkinson|date=2011-01-28|title=General Recommendations on Immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP)|work=Morbidity and Mortality Weekly Report (MMWR)|publisher=Centers for Disease Control and Prevention|url=https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6002a1.htm?s_cid=rr6002a1_e|access-date=2011-03-11|archive-date=10 July 2017|archive-url=https://web.archive.org/web/20170710182317/https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6002a1.htm?s_cid=rr6002a1_e|url-status=live}}{{Cite journal|last1=Cheuk|first1=Daniel KL|last2=Chiang|first2=Alan KS|last3=Lee|first3=Tsz Leung|last4=Chan|first4=Godfrey CF|last5=Ha|first5=Shau Yin|date=2011-03-16|title=Vaccines for prophylaxis of viral infections in patients with hematological malignancies|url=https://doi.org//10.1002/14651858.CD006505.pub2|journal=Cochrane Database of Systematic Reviews|issue=3|pages=CD006505|doi=10.1002/14651858.cd006505.pub2|pmid=21412895|issn=1465-1858|url-access=subscription}}
• Live strains typically require advanced maintenance, such as refrigeration and fresh media, making transport to remote areas difficult and costly.{{Cite journal|last=Levine|first=Myron M.|date=2011-12-30|title="IDEAL" vaccines for resource poor settings|url=http://www.sciencedirect.com/science/article/pii/S0264410X1101886X|journal=Vaccine|series=Smallpox Eradication after 30 Years: Lessons, Legacies and Innovations|language=en|volume=29|pages=D116–D125|doi=10.1016/j.vaccine.2011.11.090|pmid=22486974|issn=0264-410X|url-access=subscription}}

For many of the pathogens listed below there are many vaccines, the list below simply indicates that there are one (or more) attenuated vaccines for that particular pathogen, not that all vaccines for that pathogen are attenuated.{{cn|date=May 2023}}

• Anthrax vaccine{{Cite journal|last1=Donegan|first1=Sarah|last2=Bellamy|first2=Richard|last3=Gamble|first3=Carrol L|date=2009-04-15|title=Vaccines for preventing anthrax|url= |journal=Cochrane Database of Systematic Reviews|volume=2009 |issue=2|pages=CD006403|doi=10.1002/14651858.cd006403.pub2|issn=1465-1858|pmc=6532564|pmid=19370633}}
• Cholera vaccine{{Cite journal|last=Harris|first=Jason B|date=2018-11-15|title=Cholera: Immunity and Prospects in Vaccine Development|journal=The Journal of Infectious Diseases|volume=218|issue=Suppl 3|pages=S141–S146|doi=10.1093/infdis/jiy414|issn=0022-1899|pmc=6188552|pmid=30184117}}
• Plague vaccine{{Cite journal|last1=Verma|first1=Shailendra Kumar|last2=Tuteja|first2=Urmil|date=2016-12-14|title=Plague Vaccine Development: Current Research and Future Trends|journal=Frontiers in Immunology|volume=7|page=602|doi=10.3389/fimmu.2016.00602|issn=1664-3224|pmc=5155008|pmid=28018363|doi-access=free}}
• Salmonella vaccine{{Cite journal|last1=Odey|first1=Friday|last2=Okomo|first2=Uduak|last3=Oyo-Ita|first3=Angela|date=2018-12-05|title=Vaccines for preventing invasive salmonella infections in people with sickle cell disease|url= |journal=Cochrane Database of Systematic Reviews|volume=12|issue=4|pages=CD006975|doi=10.1002/14651858.cd006975.pub4|issn=1465-1858|pmc=6517230|pmid=30521695}}
• Tuberculosis vaccine{{Cite journal|last1=Schrager|first1=Lewis K.|last2=Harris|first2=Rebecca C.|last3=Vekemans|first3=Johan|date=2019-02-24|title=Research and development of new tuberculosis vaccines: a review|journal=F1000Research|volume=7|page=1732|doi=10.12688/f1000research.16521.2|issn=2046-1402|pmc=6305224|pmid=30613395 |doi-access=free }}
• Typhoid vaccine{{Cite journal|last1=Meiring|first1=James E|last2=Giubilini|first2=Alberto|last3=Savulescu|first3=Julian|last4=Pitzer|first4=Virginia E|last5=Pollard|first5=Andrew J|date=2019-11-01|title=Generating the Evidence for Typhoid Vaccine Introduction: Considerations for Global Disease Burden Estimates and Vaccine Testing Through Human Challenge|journal=Clinical Infectious Diseases|volume=69|issue=Suppl 5|pages=S402–S407|doi=10.1093/cid/ciz630|issn=1058-4838|pmc=6792111|pmid=31612941}}

• Live attenuated influenza vaccine (LAIV){{Cite journal|last1=Jefferson|first1=Tom|last2=Rivetti|first2=Alessandro|last3=Di Pietrantonj|first3=Carlo|last4=Demicheli|first4=Vittorio|date=2018-02-01|title=Vaccines for preventing influenza in healthy children|url= |journal=Cochrane Database of Systematic Reviews|volume=2018|issue=2 |pages=CD004879|doi=10.1002/14651858.cd004879.pub5|issn=1465-1858|pmc=6491174|pmid=29388195}}
• Japanese encephalitis vaccine{{Cite journal|last1=Yun|first1=Sang-Im|last2=Lee|first2=Young-Min|date=2014-02-01|title=Japanese encephalitis|journal=Human Vaccines & Immunotherapeutics|volume=10|issue=2|pages=263–279|doi=10.4161/hv.26902|issn=2164-5515|pmc=4185882|pmid=24161909}}
• Measles vaccine{{Cite journal|last=Griffin|first=Diane E.|date=2018-03-01|title=Measles Vaccine|journal=Viral Immunology|volume=31|issue=2|pages=86–95|doi=10.1089/vim.2017.0143|issn=0882-8245|pmc=5863094|pmid=29256824}}
• Mumps vaccine{{Cite journal|last1=Su|first1=Shih-Bin|last2=Chang|first2=Hsiao-Liang|last3=Chen|first3=And Kow-Tong|date=5 March 2020|title=Current Status of Mumps Virus Infection: Epidemiology, Pathogenesis, and Vaccine|journal=International Journal of Environmental Research and Public Health|volume=17|issue=5|page=1686|doi=10.3390/ijerph17051686|issn=1660-4601|pmc=7084951|pmid=32150969|doi-access=free}}
• Measles and rubella (MR) vaccine{{Cite journal|date=May 2014|title=Observed Rate of Vaccine Reactions – Measles, Mumps and Rubella Vaccines|url=https://www.who.int/vaccine_safety/initiative/tools/MMR_vaccine_rates_information_sheet.pdf|journal=World Health Organization Information Sheet|access-date=2 November 2020|archive-date=17 December 2019|archive-url=https://web.archive.org/web/20191217095809/https://www.who.int/vaccine_safety/initiative/tools/MMR_vaccine_rates_information_sheet.pdf|url-status=live}}
• Measles, mumps, and rubella (MMR) vaccine{{Cite journal|last1=Di Pietrantonj|first1=Carlo|last2=Rivetti|first2=Alessandro|last3=Marchione|first3=Pasquale|last4=Debalini|first4=Maria Grazia|last5=Demicheli|first5=Vittorio|date=April 20, 2020|title=Vaccines for measles, mumps, rubella, and varicella in children|journal=The Cochrane Database of Systematic Reviews|volume=4|issue=4 |pages=CD004407|doi=10.1002/14651858.CD004407.pub4|issn=1469-493X|pmc=7169657|pmid=32309885}}
• Measles, mumps, rubella and varicella (MMRV) vaccine
• Polio vaccine{{Cite journal|last1=Bandyopadhyay|first1=Ananda S.|last2=Garon|first2=Julie|last3=Seib|first3=Katherine|last4=Orenstein|first4=Walter A.|date=2015|title=Polio vaccination: past, present and future|journal=Future Microbiology|volume=10|issue=5|pages=791–808|doi=10.2217/fmb.15.19|issn=1746-0921|pmid=25824845|doi-access=free}}
• Rotavirus vaccine{{Cite journal|last1=Bruijning-Verhagen|first1=Patricia|last2=Groome|first2=Michelle|date=July 2017|title=Rotavirus Vaccine: Current Use and Future Considerations|url=https://pubmed.ncbi.nlm.nih.gov/28383393|journal=The Pediatric Infectious Disease Journal|volume=36|issue=7|pages=676–678|doi=10.1097/INF.0000000000001594|issn=1532-0987|pmid=28383393|s2cid=41278475|access-date=2 November 2020|archive-date=25 January 2023|archive-url=https://web.archive.org/web/20230125194530/https://pubmed.ncbi.nlm.nih.gov/28383393/|url-status=live}}
• Rubella vaccine{{Cite journal|last1=Lambert|first1=Nathaniel|last2=Strebel|first2=Peter|last3=Orenstein|first3=Walter|last4=Icenogle|first4=Joseph|last5=Poland|first5=Gregory A.|date=2015-06-06|title=Rubella|journal=Lancet|volume=385|issue=9984|pages=2297–2307|doi=10.1016/S0140-6736(14)60539-0|issn=0140-6736|pmc=4514442|pmid=25576992}}
• Smallpox vaccine{{Cite journal|last1=Voigt|first1=Emily A.|last2=Kennedy|first2=Richard B.|last3=Poland|first3=Gregory A.|date=September 2016|title=Defending against smallpox: a focus on vaccines|journal=Expert Review of Vaccines|volume=15|issue=9|pages=1197–1211|doi=10.1080/14760584.2016.1175305|issn=1744-8395|pmc=5003177|pmid=27049653}}
• Varicella vaccine{{Cite journal|last1=Marin|first1=Mona|last2=Marti|first2=Melanie|last3=Kambhampati|first3=Anita|last4=Jeram|first4=Stanley M.|last5=Seward|first5=Jane F.|date=March 1, 2016|title=Global Varicella Vaccine Effectiveness: A Meta-analysis|journal=Pediatrics|volume=137|issue=3|pages=e20153741|doi=10.1542/peds.2015-3741|issn=1098-4275|pmid=26908671|s2cid=25263970|doi-access=free}}
• Yellow fever vaccine{{Cite journal|last1=Monath|first1=Thomas P.|last2=Vasconcelos|first2=Pedro F. C.|date=March 2015|title=Yellow fever|url=https://pubmed.ncbi.nlm.nih.gov/25453327|journal=Journal of Clinical Virology|volume=64|pages=160–173|doi=10.1016/j.jcv.2014.08.030|issn=1873-5967|pmid=25453327|s2cid=5124080|access-date=2 November 2020|archive-date=25 January 2023|archive-url=https://web.archive.org/web/20230125194530/https://pubmed.ncbi.nlm.nih.gov/25453327/|url-status=live}}
• Zoster/shingles vaccine{{Cite journal|last=Schmader|first=Kenneth|date=August 7, 2018|title=Herpes Zoster|url=https://pubmed.ncbi.nlm.nih.gov/30083718/|journal=Annals of Internal Medicine|volume=169|issue=3|pages=ITC19–ITC31|doi=10.7326/AITC201808070|issn=1539-3704|pmid=30083718|s2cid=51926613|access-date=2 November 2020|archive-date=24 October 2022|archive-url=https://web.archive.org/web/20221024134519/https://pubmed.ncbi.nlm.nih.gov/30083718/|url-status=live}}

• Enterotoxigenic Escherichia coli vaccine{{Cite journal|last1=Mirhoseini|first1=Ali|last2=Amani|first2=Jafar|last3=Nazarian|first3=Shahram|date=April 2018|title=Review on pathogenicity mechanism of enterotoxigenic Escherichia coli and vaccines against it|url=https://pubmed.ncbi.nlm.nih.gov/29474827/|journal=Microbial Pathogenesis|volume=117|pages=162–169|doi=10.1016/j.micpath.2018.02.032|issn=1096-1208|pmid=29474827|access-date=2 November 2020|archive-date=23 January 2023|archive-url=https://web.archive.org/web/20230123231903/https://pubmed.ncbi.nlm.nih.gov/29474827/|url-status=live}}

• Tick-borne encephalitis vaccine{{Cite journal|last1=Kubinski|first1=Mareike|last2=Beicht|first2=Jana|last3=Gerlach|first3=Thomas|last4=Volz|first4=Asisa|last5=Sutter|first5=Gerd|last6=Rimmelzwaan|first6=Guus F.|date=2020-08-12|title=Tick-Borne Encephalitis Virus: A Quest for Better Vaccines against a Virus on the Rise|journal=Vaccines|volume=8|issue=3|page=451|doi=10.3390/vaccines8030451|issn=2076-393X|pmc=7564546|pmid=32806696|doi-access=free}}
• COVID-19{{cite web |title=Safety and Immunogenicity of COVI-VAC, a Live Attenuated Vaccine Against COVID-19 |url=https://clinicaltrials.gov/ct2/show/NCT04619628 |website=ClinicalTrials.gov |publisher=United States National Library of Medicine |access-date=8 June 2021 |archive-date=22 January 2021 |archive-url=https://web.archive.org/web/20210122001432/https://clinicaltrials.gov/ct2/show/NCT04619628 |url-status=live }}

{{Reflist}}

{{Scholia}}

• [https://web.archive.org/web/20070604164605/http://www.polioeradication.org/vaccines.asp Global Polio Eradication Initiative: Advantages and Disadvantages of Vaccine Types]
• [https://www.cdc.gov/h1n1flu/vaccination/nasalspray_qa.htm CDC H1N1 Flu / 2009 H1N1 Nasal Spray Vaccine Q&A] at the website of the US Centers for Disease Control and Prevention

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