hepatitis B vaccine

In the United States vaccination is recommended for nearly all babies at birth.{{cite journal | author1 = Committee on Infectious Diseases | author2 = Committee On Fetus And Newborn | title = Elimination of Perinatal Hepatitis B: Providing the First Vaccine Dose Within 24 Hours of Birth | journal = Pediatrics | volume = 140 | issue = 3 | pages = e20171870 | date = September 2017 | pmid = 28847980 | doi = 10.1542/peds.2017-1870 | doi-access = free }} Many countries routinely vaccinate infants against hepatitis B. In countries with high rates of hepatitis B infection, vaccination of newborns has not only reduced the risk of infection but has also led to a marked reduction in liver cancer. This was reported in Taiwan where the implementation of a nationwide hepatitis B vaccination program in 1984 was associated with a decline in the incidence of childhood hepatocellular carcinoma.{{cite journal | vauthors = Chang MH, Chen CJ, Lai MS, Hsu HM, Wu TC, Kong MS, Liang DC, Shau WY, Chen DS |author1-link=Chang Mei-hwei |author9-link=Ding-Shinn Chen | title = Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group | journal = The New England Journal of Medicine | volume = 336 | issue = 26 | pages = 1855–9 | date = June 1997 | pmid = 9197213 | doi = 10.1056/NEJM199706263362602 | doi-access = free }}

In the UK, the vaccine is offered to men who have sex with men (MSM), usually as part of a sexual health check-up. A similar situation is in operation in Ireland.{{cite web|url=http://www.nhs.uk/Conditions/vaccinations/Pages/hepatitis-b-vaccine.aspx|title=Hepatitis B vaccine|website=Nhs.uk|access-date=27 April 2017|url-status=live|archive-url=https://web.archive.org/web/20170628184633/http://www.nhs.uk/Conditions/vaccinations/Pages/hepatitis-b-vaccine.aspx|archive-date=28 June 2017}}

In many areas, vaccination against hepatitis B is also required for all health-care and laboratory staff.{{cite book|author=Joint Committee on Vaccination and Immunisation|title=Immunisation Against Infectious Disease 2006 ("The Green Book")|edition=3rd|chapter=Chapter 12 Immunisation of healthcare and laboratory staff—Hepatitis B|chapter-url=http://www.dh.gov.uk/en/Publichealth/Healthprotection/Immunisation/Greenbook/DH_4097254?IdcService=GET_FILE&dID=115800&Rendition=Web|chapter-format=PDF|publisher=Stationery Office|location=Edinburgh|year=2006|page=468|isbn=978-0-11-322528-6|access-date=25 March 2008|archive-date=7 January 2013|archive-url=http://webarchive.nationalarchives.gov.uk/20130107105354/http://www.dh.gov.uk/en/Publichealth/Healthprotection/Immunisation/Greenbook/DH_4097254?IdcService=GET_FILE&dID=115800&Rendition=Web|url-status=dead}} Both types of the vaccine, the plasma-derived vaccine (PDV) and recombinant vaccine (RV), seems to be able to elicit similar protective anti-HBs levels.

The US Centers for Disease Control and Prevention (CDC) issued recommendations for vaccination against hepatitis B among patients with diabetes mellitus.{{cite journal | title = Use of hepatitis B vaccination for adults with diabetes mellitus: recommendations of the Advisory Committee on Immunization Practices (ACIP) | journal = MMWR Morb. Mortal. Wkly. Rep. | volume = 60 | issue = 50 | pages = 1709–11 | date = December 2011 | pmid = 22189894 | url = https://www.cdc.gov/mmwr/pdf/wk/mm6050.pdf | author1 = U.S. Centers for Disease Control and Prevention (CDC) | access-date = 7 May 2020 | archive-date = 17 October 2020 | archive-url = https://web.archive.org/web/20201017141007/https://www.cdc.gov/mmwr/pdf/wk/mm6050.pdf | url-status = live }} The World Health Organization (WHO) recommends a pentavalent vaccine, combining vaccines against diphtheria, tetanus, pertussis and Haemophilus influenzae type B with the vaccine against hepatitis B.{{medical citation needed|date=September 2019}} There is not yet sufficient evidence on how effective this pentavalent vaccine is compared to the individual vaccines.{{cite journal | vauthors = Bar-On ES, Goldberg E, Hellmann S, Leibovici L | title = Combined DTP–HBV–HIB vaccine versus separately administered DTP–HBV and HIB vaccines for primary prevention of diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae B (HIB) | journal = The Cochrane Database of Systematic Reviews | volume = 2012 | issue = 4 | pages = CD005530 | date = April 2012 | pmid = 22513932 | doi = 10.1002/14651858.CD005530.pub3 | pmc = 11440342 }} A pentavalent vaccine combining vaccines against diphtheria, tetanus, pertussis, hepatitis B, and poliomyelitis is approved in the U.S. and is recommended by the Advisory Committee on Immunization Practices (ACIP).{{cite journal |title=FDA licensure of diphtheria and tetanus toxoids and acellular pertussis adsorbed, hepatitis B (recombinant), and poliovirus vaccine combined, (PEDIARIX) for use in infants |journal=MMWR Morb. Mortal. Wkly. Rep. |volume=52 |issue=10 |pages=203–4 |date=March 2003 |pmid=12653460 |author1=U.S. Centers for Disease Control and Prevention (CDC) }}{{cite journal |title=Licensure of a diphtheria and tetanus toxoids and acellular pertussis adsorbed and inactivated poliovirus vaccine and guidance for use as a booster dose |journal=MMWR Morb. Mortal. Wkly. Rep. |volume=57 |issue=39 |pages=1078–9 |date=October 2008 |pmid=18830212 |url=https://www.cdc.gov/mmwr/volumes/69/wr/pdfs/mm6905a5-H.pdf |author1=U.S. Centers for Disease Control and Prevention (CDC) |access-date=7 May 2020 |archive-date=7 May 2020 |archive-url=https://web.archive.org/web/20200507204934/https://www.cdc.gov/mmwr/volumes/69/wr/pdfs/mm6905a5-H.pdf |url-status=live }}{{cite journal |vauthors=Schillie S, Vellozzi C, Reingold A, Harris A, Haber P, Ward JW, Nelson NP |title=Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices |journal=MMWR Recomm Rep |volume=67 |issue=1 |pages=1–31 |date=January 2018 |pmid=29939980 |pmc=5837403 |doi=10.15585/mmwr.rr6701a1 |url=https://www.cdc.gov/mmwr/volumes/67/rr/pdfs/rr6701-H.PDF |access-date=7 May 2020 |archive-date=3 July 2020 |archive-url=https://web.archive.org/web/20200703073214/https://www.cdc.gov/mmwr/volumes/67/rr/pdfs/rr6701-H.PDF |url-status=live }}

Hepatitis B vaccination, hepatitis B immunoglobulin, and the combination of hepatitis B vaccine plus hepatitis B immunoglobulin, all are considered as preventive for babies born to mothers infected with hepatitis B virus (HBV).{{cite journal|vauthors=Lee C, Gong Y, Brok J, Boxall EH, Gluud C|date=April 2006|title=Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers|journal=The Cochrane Database of Systematic Reviews|issue=2|pages=CD004790|doi=10.1002/14651858.CD004790.pub2|pmid=16625613}} The combination is superior for protecting these infants. The effectiveness of being vaccinated during pregnancy to prevent vertical transmission of hepatitis B to infants has not been studied.{{cite journal|vauthors=Sangkomkamhang US, Lumbiganon P, Laopaiboon M|date=November 2014|title=Hepatitis B vaccination during pregnancy for preventing infant infection|journal=The Cochrane Database of Systematic Reviews|volume=2014 |issue=11|pages=CD007879|doi=10.1002/14651858.CD007879.pub3|pmc=7185858|pmid=25385500}} Hepatitis B immunoglobulin before birth has not been well studied.{{cite journal|vauthors=Eke AC, Eleje GU, Eke UA, Xia Y, Liu J|date=February 2017|title=Hepatitis B immunoglobulin during pregnancy for prevention of mother-to-child transmission of hepatitis B virus|journal=The Cochrane Database of Systematic Reviews|volume=2017|issue=2 |pages=CD008545|doi=10.1002/14651858.CD008545.pub2|pmc=6464495|pmid=28188612}}

Studies have found that that immune memory against HepB is sustained for at least 30 years after vaccination, and protects against clinical disease and chronic HepB infection, even in cases where anti-hepatitis B surface antigen (anti-Hbs) levels decline below detectable levels.{{cite web |title=Ask the Experts: Hepatitis B |url=https://www.immunize.org/askexperts/experts_hepb.asp |website=Immunize.org |publisher=Immunization Action Coalition |access-date=25 September 2022 |date=26 May 2022 |archive-date=16 October 2022 |archive-url=https://web.archive.org/web/20221016004631/https://www.immunize.org/askexperts/experts_hepb.asp |url-status=live }} Testing to confirm successful immunization or sustained immunity is not necessary or recommended for most people, but is recommended for infants born to a mother who tests positive for HBsAg or whose HBsAg status is not known; for healthcare and public safety workers; for immunocompromised people such as haemodialysis patients, HIV patients, haematopoietic stem cell transplant [HSCT] recipients, or people receiving chemotherapy; and for sexual partners of HBsAg-positive people.

An anti-Hbs antibody level above 100{{nbsp}}mIU/ml is deemed adequate and occurs in about 85–90% of individuals. An antibody level between 10 and 100{{nbsp}}mIU/ml is considered a poor response, and these people should receive a single booster vaccination at this time, but do not need further retesting. People who fail to respond (anti-Hbs antibody level below 10{{nbsp}}mIU/ml) should be tested to exclude current or past hepatitis B infection, and given a repeat course of three vaccinations, followed by further retesting 1–4 months after the second course. Those who still do not respond to a second course of vaccination may respond to intradermal injection or to a high dose vaccine{{cite journal | vauthors = Levitz RE, Cooper BW, Regan HC | title = Immunization with high-dose intradermal recombinant hepatitis B vaccine in healthcare workers who failed to respond to intramuscular vaccination | journal = Infection Control and Hospital Epidemiology | volume = 16 | issue = 2 | pages = 88–91 | date = February 1995 | pmid = 7759824 | doi = 10.1086/647062 }} or to a double dose of a combined hepatitis A and B vaccine.{{cite journal | vauthors = Cardell K, Akerlind B, Sällberg M, Frydén A | title = Excellent response rate to a double dose of the combined hepatitis A and B vaccine in previous nonresponders to hepatitis B vaccine | journal = The Journal of Infectious Diseases | volume = 198 | issue = 3 | pages = 299–304 | date = August 2008 | pmid = 18544037 | doi = 10.1086/589722 | doi-access = free }} Those who still fail to respond will require hepatitis B immunoglobulin (HBIG) if later exposed to the hepatitis B virus.

Poor responses are mostly associated with being over the age of 40 years, obesity, celiac disease, and tobacco smoking,{{cite journal | vauthors=Filippelli M, Lionetti E, Gennaro A, Lanzafame A, Arrigo T, Salpietro C, La Rosa M, Leonardi S |title=Hepatitis B vaccine by intradermal route in non responder patients: an update |journal=World J. Gastroenterol. |date=August 2014 |volume=20 |issue=30 |pages=10383–94 |doi=10.3748/wjg.v20.i30.10383 |pmid=25132754|pmc=4130845|type=Review |doi-access=free }}{{cite journal | vauthors = Roome AJ, Walsh SJ, Cartter ML, Hadler JL | title = Hepatitis B vaccine responsiveness in Connecticut public safety personnel | journal = JAMA | volume = 270 | issue = 24 | pages = 2931–4 | year = 1993 | pmid = 8254852 | doi = 10.1001/jama.270.24.2931 }} and also in alcoholics, especially if with advanced liver disease.{{cite journal | vauthors = Rosman AS, Basu P, Galvin K, Lieber CS | title = Efficacy of a high and accelerated dose of hepatitis B vaccine in alcoholic patients: a randomized clinical trial | journal = The American Journal of Medicine | volume = 103 | issue = 3 | pages = 217–22 | date = September 1997 | pmid = 9316554 | doi = 10.1016/S0002-9343(97)00132-0 }} People who are immunosuppressed or on dialysis may not respond as well and require larger or more frequent doses of vaccine. At least one study suggests that hepatitis B vaccination is less effective in patients with HIV.{{cite journal | vauthors = Pasricha N, Datta U, Chawla Y, Singh S, Arora SK, Sud A, Minz RW, Saikia B, Singh H, James I, Sehgal S | title = Immune responses in patients with HIV infection after vaccination with recombinant Hepatitis B virus vaccine | journal = BMC Infectious Diseases | volume = 6 | pages = 65 | date = March 2006 | pmid = 16571140 | pmc = 1525180 | doi = 10.1186/1471-2334-6-65 | doi-access = free }} Cold or Flu-like symptoms can develop after receiving the vaccine, but these are short-lived. As with any injection, the muscle can become tender around the injection point for some time afterward The immune response to the hepatitis B vaccine can be impaired by the presence of parasitic infections such as helminthiasis.{{cite journal | vauthors = Natukunda A, Zirimenya L, Nassuuna J, Nkurunungi G, Cose S, Elliott AM, Webb EL | title = The effect of helminth infection on vaccine responses in humans and animal models: A systematic review and meta-analysis | journal = Parasite Immunology | volume = 44 | issue = 9 | pages = e12939 | date = September 2022 | pmid = 35712983 | pmc = 9542036 | doi = 10.1111/pim.12939 }}

The HepB vaccine is vital for use for infants who contract HepB. 90% of infants who contract HepB and do not receive the vaccination will develop chronic infection.{{Cite web |last=CDC |date=2024-11-26 |title=Fast Facts |url=https://www.cdc.gov/global-hepatitis-b-vaccination/data-research/index.html |access-date=2025-04-02 |website=Global Hepatitis B Vaccination |language=en-us}} And these chronic HBV infections are life-threatening, with a 15–25% risk of death from complications.

The Hepatitis B vaccine is now believed to provide indefinite protection. Older literature assumed that immunity would wane with antibody titers and only effectively last five to seven years,{{cite journal | vauthors = Krugman S, Davidson M | title = Hepatitis B vaccine: prospects for duration of immunity | journal = The Yale Journal of Biology and Medicine | volume = 60 | issue = 4 | pages = 333–9 | year = 1987 | pmid = 3660859 | pmc = 2590237 }}{{cite journal | vauthors = Petersen KM, Bulkow LR, McMahon BJ, Zanis C, Getty M, Peters H, Parkinson AJ | title = Duration of hepatitis B immunity in low risk children receiving hepatitis B vaccinations from birth | journal = The Pediatric Infectious Disease Journal | volume = 23 | issue = 7 | pages = 650–5 | date = July 2004 | pmid = 15247604 | doi = 10.1097/01.inf.0000130952.96259.fd | s2cid = 10541868 | url = http://www.medscape.com/viewarticle/483473 | format = Free full text | archive-url = https://web.archive.org/web/20150605151824/http://www.medscape.com/viewarticle/483473 | url-status = live | archive-date = 5 June 2015 }} but immune-challenge studies show that even after 30 years, the immune system maintains the ability to produce an anamnestic response, i.e. to rapidly bump up antibody levels when the previously seen antigen is detected.{{cite journal | vauthors = Van Damme P, Van Herck K | title = A review of the long-term protection after hepatitis A and B vaccination | journal = Travel Medicine and Infectious Disease | volume = 5 | issue = 2 | pages = 79–84 | date = March 2007 | pmid = 17298912 | doi = 10.1016/j.tmaid.2006.04.004 }}{{cite journal | vauthors = Van Damme P | title = Long-term Protection After Hepatitis B Vaccine | journal = The Journal of Infectious Diseases | volume = 214 | issue = 1 | pages = 1–3 | date = July 2016 | pmid = 26802140 | doi = 10.1093/infdis/jiv750 | doi-access = free }} This shows that the immunological memory is not affected by the loss of antibody levels. As a result, subsequent antibody testing and administration of booster doses is not required in successfully vaccinated immunocompetent individuals.{{cite journal | vauthors = Gabbuti A, Romanò L, Blanc P, Meacci F, Amendola A, Mele A, Mazzotta F, Zanetti AR | title = Long-term immunogenicity of hepatitis B vaccination in a cohort of Italian healthy adolescents | journal = Vaccine | volume = 25 | issue = 16 | pages = 3129–32 | date = April 2007 | pmid = 17291637 | doi = 10.1016/j.vaccine.2007.01.045 }}{{cite journal | title = Are booster immunisations needed for lifelong hepatitis B immunity? European Consensus Group on Hepatitis B Immunity | journal = Lancet | volume = 355 | issue = 9203 | pages = 561–5 | date = February 2000 | pmid = 10683019 | doi = 10.1016/S0140-6736(99)07239-6 | s2cid = 32401362 }} UK guidelines suggest that people who respond to the vaccine and are at risk of occupational exposure, such as for healthcare workers, a single booster is recommended five years after initial immunization.{{cite book|author=Joint Committee on Vaccination and Immunisation|title=Immunisation Against Infectious Disease 2006 ("The Green Book")|edition=3rd edition (Chapter 18 revised 10 October 2007)|chapter=Chapter 18: Hepatitis B|chapter-url=http://www.dh.gov.uk/en/Publichealth/Healthprotection/Immunisation/Greenbook/DH_4097254?IdcService=GET_FILE&dID=152019&Rendition=Web |chapter-format=PDF |publisher=Stationery Office |location=Edinburgh|year=2006|page=468|isbn=978-0-11-322528-6 |url-status=dead |archive-url= http://webarchive.nationalarchives.gov.uk/20130107105354/http://www.dh.gov.uk/en/Publichealth/Healthprotection/Immunisation/Greenbook/DH_4097254?IdcService=GET_FILE&dID=152019&Rendition=Web|archive-date=7 January 2013}}

Serious side effects from the hepatitis B vaccine are very rare. Pain may occur at the site of injection. It is generally considered safe for use, during pregnancy or while breastfeeding.{{cite journal | vauthors = Borgia G, Carleo MA, Gaeta GB, Gentile I | title = Hepatitis B in pregnancy | journal = World Journal of Gastroenterology | volume = 18 | issue = 34 | pages = 4677–83 | date = September 2012 | pmid = 23002336 | pmc = 3442205 | doi = 10.3748/wjg.v18.i34.4677 | doi-access = free }} It has not been linked to Guillain–Barré syndrome.

Several studies have looked for an association between recombinant hepatitis B vaccine and multiple sclerosis (MS) in adults.{{cite journal | vauthors = Martínez-Sernández V, Figueiras A | title = Central nervous system demyelinating diseases and recombinant hepatitis B vaccination: a critical systematic review of scientific production | journal = Journal of Neurology | volume = 260 | issue = 8 | pages = 1951–9 | date = August 2013 | pmid = 23086181 | doi = 10.1007/s00415-012-6716-y | s2cid = 20362426 | doi-access = free }} Most studies do not support a causal relationship between hepatitis B vaccination and demyelinating diseases such as MS.{{cite web|url=https://www.cdc.gov/vaccinesafety/Vaccines/multiplesclerosis_and_hep_b.html |title=FAQs about Hepatitis B Vaccine (Hep B) and Multiple Sclerosis |publisher=U.S. Centers for Disease Control and Prevention (CDC)|date=9 October 2009|url-status=live|archive-url=https://web.archive.org/web/20091110171124/http://www.cdc.gov/vaccinesafety/Vaccines/multiplesclerosis_and_hep_b.html|archive-date=10 November 2009}}{{cite journal | vauthors=Mouchet J, Salvo F, Raschi E, Poluzzi E, Antonazzo IC, De Ponti F, Bégaud B |title=Hepatitis B vaccination and the putative risk of central demyelinating diseases – A systematic review and meta-analysis |journal=Vaccine |date=March 2018 |volume=36 |issue=12 |pages=1548–55 |doi=10.1016/j.vaccine.2018.02.036 |pmid=29454521}} A 2004 study reported a significant increase in risk within three years of vaccination. Some of these studies were criticized for methodological problems.{{cite journal | vauthors = Hernán MA, Jick SS, Olek MJ, Jick H | title = Recombinant hepatitis B vaccine and the risk of multiple sclerosis: a prospective study | journal = Neurology | volume = 63 | issue = 5 | pages = 838–42 | date = September 2004 | pmid = 15365133 | doi = 10.1212/01.WNL.0000138433.61870.82 | s2cid = 25309517 }} This controversy created public misgivings about hepatitis B vaccination, and hepatitis B vaccination in children remained low in several countries. A 2006 study concluded that evidence did not support an association between hepatitis B vaccination and sudden infant death syndrome, chronic fatigue syndrome, or multiple sclerosis.{{cite journal | vauthors = Zuckerman JN | title = Protective efficacy, immunotherapeutic potential, and safety of hepatitis B vaccines | journal = Journal of Medical Virology | volume = 78 | issue = 2 | pages = 169–77 | date = February 2006 | pmid = 16372285 | doi = 10.1002/jmv.20524 | s2cid = 45526262 }} A 2007 study found that the vaccination does not seem to increase the risk of a first episode of MS in childhood.{{cite journal | vauthors = Mikaeloff Y, Caridade G, Rossier M, Suissa S, Tardieu M | title = Hepatitis B vaccination and the risk of childhood-onset multiple sclerosis | journal = Archives of Pediatrics & Adolescent Medicine | volume = 161 | issue = 12 | pages = 1176–82 | date = December 2007 | pmid = 18056563 | doi = 10.1001/archpedi.161.12.1176 | doi-access = free }} Hepatitis B vaccination has not been linked to onset of autoimmune diseases in adulthood.{{cite journal |vauthors=Elwood JM, Ameratunga R |title=Autoimmune diseases after hepatitis B immunization in adults: Literature review and meta-analysis, with reference to 'autoimmune/autoinflammatory syndrome induced by adjuvants' (ASIA) |journal=Vaccine |date=September 2018 |volume=36 |issue=38 |pages=5796–5802 |doi=10.1016/j.vaccine.2018.07.074 |pmid=30100071|s2cid=51967163 |type=Review}}

File:Immunization-hepb3-of-one-year-old-children.png

The following is a list of countries by the percentage of infants receiving three doses of hepatitis B vaccine as published by the World Health Organization (WHO) in 2017 compared to 2022.{{Cite web |title=GHO {{!}} By category {{!}} Hepatitis B (HepB3) – Immunization coverage estimates by country |url=https://apps.who.int/gho/data/view.main.80300?lang=en |access-date=2025-04-04 |website=WHO}}

According to the CDC, 34.2% of all adults over the age of 18 in the United States have received at least one HepB vaccine.{{Cite web |last=CDC |date=2024-07-31 |title=Vaccination Coverage among Adults in the United States, National Health Interview Survey, 2021 |url=https://www.cdc.gov/adultvaxview/publications-resources/vaccination-coverage-adults-2021.html#:~:text=Hepatitis%20B%20vaccination%20coverage%20in,and%20Other%20(40.2%25)%20adults. |access-date=2025-04-04 |website=AdultVaxView |language=en-us}} Vaccine uptake varies across demographics such race, age, and travel status. With 53.5% of Asian adults aged 19–49 years having had at least one HepB vaccine compared to 48.4% of White adults, 34.4% of Black adults, and 37.5% of Hispanic adults. These numbers are lower for adults aged 30–59 years; with 47.0% of Asian adults aged 30–59 having had at least one HepB vaccine, 38.4% of White adults, 31.2% of Black adults, and 31.5% of Hispanic adults. The CDC also reports higher HepB vaccine uptake for adults who travel compared to those who do not, 43.1% compared to 28.7%.

In 1963, the American physician/geneticist Baruch Blumberg, working at the Fox Chase Cancer Center, discovered what he called the "Australia Antigen" (HBsAg) in the serum of an Australian Aboriginal person.{{cite journal | vauthors = Blumberg BS, Alter HJ, Visnich S | title = A "New" Antigen In Leukemia Sera | journal = JAMA | volume = 191 | issue = 7| pages = 541–6 | date = February 1965 | pmid = 14239025 | doi = 10.1001/jama.1965.03080070025007 }} In 1968, this protein was found to be part of the virus that causes "serum hepatitis" (hepatitis B) by virologist Alfred Prince.{{cite book |author1=Howard, Colin |author2=Zuckerman, Arie J. |title=Hepatitis viruses of man |publisher=Academic Press |location=Boston |year=1979 |pages=[https://archive.org/details/hepatitisviruses0000zuck/page/16 16–18] |isbn=978-0-12-782150-4 |url=https://archive.org/details/hepatitisviruses0000zuck/page/16 }}

In 1976, Blumberg won the Nobel Prize in Physiology or Medicine for his work on hepatitis B (sharing it with Daniel Carleton Gajdusek for his work on kuru).{{Cite web|title=The Nobel Prize in Physiology or Medicine 1976|url=https://www.nobelprize.org/prizes/medicine/1976/summary/|access-date=14 February 2021|website=NobelPrize.org|language=en-US|archive-date=23 May 2020|archive-url=https://web.archive.org/web/20200523072414/https://www.nobelprize.org/prizes/medicine/1976/summary/|url-status=live}} Blumberg had identified Australia antigen, the important first step, and later discovered the way to make the first hepatitis B vaccine. Blumberg's vaccine was a unique approach to the production of a vaccine; that is, obtaining the immunizing antigen directly from the blood of human carriers of the virus. In October 1969, acting on behalf of the Institute for Cancer Research, they applied for a patent for the production of a vaccine. This patent [USP 3,636,191] was subsequently (January 1972) granted in the United States and other countries. In 2002, Blumberg published a book, Hepatitis B: The Hunt for a Killer Virus.Blumberg, Baruch (2002), Hepatitis B: The Hunt for a Killer Virus, Princeton: Princeton University Press. In the book, Blumberg wrote: “It took some time before the concept was accepted by virologists and vaccine manufacturers who were more accustomed to dealing with vaccines produced by attenuation of viruses, or the use of killed viruses produced in tissue culture, or related viruses that were non-pathogenic protective (i.e., smallpox). However, by 1971, we were able to interest Merck, which had considerable experience with vaccines."

During the next few years, a series of human and primate observations by scientists including Maurice Hilleman (who was responsible for vaccines at Merck), S. Krugman, R. Purcell, P. Maupas, and others provided additional support for the vaccine. In 1980, the results of the first field trial were published by W. Szmuness and his colleagues in New York City.

The American microbiologist/vaccinologist Maurice Hilleman at Merck used three treatments (pepsin, urea and formaldehyde) of blood serum together with rigorous filtration to yield a product that could be used as a safe vaccine. Hilleman hypothesized that he could make an HBV vaccine by injecting patients with hepatitis B surface protein. In theory, this would be very safe, as these excess surface proteins lacked infectious viral DNA. The immune system, recognizing the surface proteins as foreign, would manufacture specially shaped antibodies, custom-made to bind to, and destroy, these proteins. Then, in the future, if the patient were infected with HBV, the immune system could promptly deploy protective antibodies, destroying the viruses before they could do any harm.{{cite web |url=http://blog.advocatesaz.org/2012/07/26/world-hepatitis-day-the-history-of-the-hepatitis-b-vaccine/ |title=World Hepatitis Day: The History of the Hepatitis B Vaccine | Planned Parenthood Advocates of Arizona |website=Blog.advocatesaz.org |date=26 July 2012 |access-date=27 April 2017 |url-status=live |archive-url=https://web.archive.org/web/20160405180935/http://blog.advocatesaz.org/2012/07/26/world-hepatitis-day-the-history-of-the-hepatitis-b-vaccine/ |archive-date=5 April 2016 }}

Hilleman collected blood from gay men and intravenous drug users—groups known to be at risk for viral hepatitis. This was in the late 1970s when HIV was yet unknown to medicine. In addition to the sought-after hepatitis B surface proteins, the blood samples likely contained HIV. Hilleman devised a multistep process to purify this blood so that only the hepatitis B surface proteins remained. Every known virus was killed by this process, and Hilleman was confident that the vaccine was safe.

The first large-scale trials for the blood-derived vaccine were performed on gay men, due to their high-risk status. Later, Hilleman's vaccine was falsely blamed for igniting the AIDS epidemic. (See Wolf Szmuness) But, although the purified blood vaccine seemed questionable, it was determined to have indeed been free of HIV. The purification process had destroyed all viruses—including HIV. The vaccine was approved in 1981.

The blood-derived hepatitis B vaccine was withdrawn from the marketplace in 1986, replaced by Maurice Hilleman's improved recombinant hepatitis B vaccine which was approved by the FDA on 23 July 1986.{{Cite web | date=|title=Vaccine Development & Licensing Events|url=https://www.historyofvaccines.org/content/articles/vaccine-development-licensing-events|url-status=live|archive-url=https://web.archive.org/web/20220416044857/https://www.historyofvaccines.org/content/articles/vaccine-development-licensing-events|archive-date=16 April 2022|access-date=14 February 2021|website=History of Vaccines|language=en}} It was the first human vaccine produced by recombinant DNA methods. For this work, scientists at Merck & Co. collaborated with William J. Rutter and colleagues at the University of California at San Francisco, as well as Benjamin Hall and colleagues at the University of Washington.{{Cite web | date=February 2000|title=THE HEPATITIS B STORY|url=http://www.nasonline.org/publications/beyond-discovery/hepatitis-b-story.pdf|url-status=live|archive-url=https://web.archive.org/web/20210728101809/http://www.nasonline.org/publications/beyond-discovery/hepatitis-b-story.pdf|archive-date=28 July 2021|access-date=|website=National Academy of Sciences}} In 1981, William J. Rutter, Pablo DT Valenzuela and Edward Penhoet (UC Berkeley) co-founded the Chiron Corporation in Emeryville, California, which collaborated with Merck.{{Cite news| vauthors = Fisher LM |date=13 October 1986|title= Biotechnology Spotlight Now Shines on Chiron |language=en-US |work=The New York Times|url=https://www.nytimes.com/1986/10/13/business/biotechnology-spotlight-now-shines-on-chiron.html|access-date=14 February 2021|issn=0362-4331|archive-date=26 August 2017|archive-url=https://web.archive.org/web/20170826074715/http://www.nytimes.com/1986/10/13/business/biotechnology-spotlight-now-shines-on-chiron.html|url-status=live}}

The recombinant vaccine is based on a Hepatitis B surface antigen (HBsAg) gene inserted into yeast (Saccharomyces cerevisiae) cells which are free of any concerns associated with human blood products. This allows the yeast to produce only the noninfectious surface protein, without any danger of introducing actual viral DNA into the final product. The vaccine contains the adjuvant amorphous aluminum hydroxyphosphate sulfate.

In 2017, a two-dose HBV vaccine for adults, Heplisav-B gained U.S. Food and Drug Administration (FDA) approval.{{cite web | title=Heplisav-B | website=U.S. Food and Drug Administration (FDA) | url=https://www.fda.gov/vaccines-blood-biologics/vaccines/heplisav-b | access-date=22 September 2019 | archive-date=22 September 2019 | archive-url=https://web.archive.org/web/20190922201207/https://www.fda.gov/vaccines-blood-biologics/vaccines/heplisav-b | url-status=dead }} It uses recombinant HB surface antigen, similar to previous vaccines, but includes a novel CpG 1018 adjuvant, a 22-mer phosphorothioate-linked oligodeoxynucleotide. It was non-inferior concerning immunogenicity.{{cite web |author1=Dynavax Technologies Corp |title=Heplisav-B [Hepatitis B Vaccine (Recombinant), Adjuvanted] label |url=https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM584762.pdf |website=U.S. Food and Drug Administration (FDA) |access-date=27 November 2018 |archive-date=25 April 2018 |archive-url=https://web.archive.org/web/20180425154434/https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM584762.pdf |url-status=dead }}

In November 2021, Hepatitis B Vaccine (Recombinant) (Prehevbrio) was approved by the FDA.{{cite web | title=ACIP Evidence to Recommendations for use of PreHevbrio Hepatitis B (HepB) Vaccine in Adults | publisher=U.S. Centers for Disease Control and Prevention (CDC) | date=31 March 2022 | url=https://www.cdc.gov/vaccines/acip/recs/grade/prehevbrio-hepb-etr.html | access-date=15 February 2023 | archive-date=18 August 2022 | archive-url=https://web.archive.org/web/20220818101046/https://www.cdc.gov/vaccines/acip/recs/grade/prehevbrio-hepb-etr.html | url-status=live }}{{cite web | title=Grading of Recommendations Assessment, Development and Evaluation (GRADE): PreHevbrio for Adults | publisher=U.S. Centers for Disease Control and Prevention (CDC) | date=31 March 2022 | url=https://www.cdc.gov/vaccines/acip/recs/grade/prehevbrio-hepb.html | access-date=15 February 2023 | archive-date=3 December 2022 | archive-url=https://web.archive.org/web/20221203141725/https://www.cdc.gov/vaccines/acip/recs/grade/prehevbrio-hepb.html | url-status=live }}{{cite journal | vauthors = Murthy N, Wodi AP, McNally V, Cineas S, Ault K | title = Advisory Committee on Immunization Practices Recommended Immunization Schedule for Adults Aged 19 Years or Older – United States, 2023 | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 72 | issue = 6 | pages = 141–144 | date = February 2023 | pmid = 36757861 | pmc = 9925137 | doi = 10.15585/mmwr.mm7206a2 | url = https://www.cdc.gov/mmwr/volumes/72/wr/pdfs/mm7206a2-H.pdf | access-date = 16 February 2023 | url-status = live | archive-url = https://web.archive.org/web/20230209183614/https://www.cdc.gov/mmwr/volumes/72/wr/pdfs/mm7206a2-H.pdf | archive-date = 9 February 2023 }}

The US CDC ACIP first recommended the vaccine for all newborns in 1991.{{cite journal |url=https://www.cdc.gov/mmwr/preview/mmwrhtml/00033405.htm |title=Hepatitis B Virus: A Comprehensive Strategy for Eliminating Transmission in the United States Through Universal Childhood Vaccination: Recommendations of the Immunization Practices Advisory Committee |journal=MMWR |date=22 November 1991|volume=40 |issue=RR-13 |pages=1–19 |pmid=1835756 |access-date=15 May 2023}} Before this, the vaccine was only recommended for high-risk groups. As of the 1991 recommendation for universal newborn Hepatitis B vaccination, no other vaccines were routinely recommended for all newborns in the United States and remains one of the very few vaccines routinely recommended for administration at birth.

The CDC has varying Hepatitis B vaccination schedule recommendations depending on the birth weight of the infant and Hepatitis B status of the birth mother. For infants born to mothers with a negative Hepatitis B antigen test, who weight at least 2000 grams, the first Hepatitis B vaccination is recommended in the first 24 hours of life, the second dose between 1 and 2 months, and the third dose between 6 and 18 months.{{Cite journal |last=Hawkins |first=Summer Sherburne |date=2024-11-01 |title=Long-term Implications and Barriers to Use of the Hepatitis B Vaccine at Birth |url=https://linkinghub.elsevier.com/retrieve/pii/S0884217524002995 |journal=Journal of Obstetric, Gynecologic & Neonatal Nursing |language=English |volume=53 |issue=6 |pages=594–606 |doi=10.1016/j.jogn.2024.09.008 |issn=0884-2175 |pmid=39389550|url-access=subscription }} For infants born to mothers with a negative Hepatitis B antigen test, who weight less than 2000 grams, the first Hepatitis B vaccination is recommended at 1 months of age or hospital discharge (whichever comes first). For infants born to Hepatitis B positive mothers, Hepatitis B vaccine is recommended in the first 12 hours of birth as well as administration of Hepatitis B immune globulin. For infants born to mothers with an unknown Hepatitis B status, Hepatitis B vaccination is recommended in the first 12 hours of life. For infants born to mothers with positive or unknown Hepatitis B status, a follow up screening is recommended between 9 and 12 months.

The vaccine contains one of the viral envelope proteins, Hepatitis B surface antigen (HBsAg). It is produced by yeast cells, into which the gene for HBsAg has been inserted.{{cite web |url=http://www.rxlist.com/recombivax-drug.htm |title=Hepatitis B Vaccine from Merck |access-date=9 May 2010 |url-status=live |archive-url= https://web.archive.org/web/20100421000459/http://www.rxlist.com/recombivax-drug.htm|archive-date=21 April 2010 }} Afterward an immune system antibody to HBsAg is established in the bloodstream. The antibody is known as anti-HBs. This antibody and immune system memory then provide immunity to hepatitis B virus (HBV) infection.{{cite web |url=https://www.cdc.gov/hepatitis/index.htm |title=CDC Viral Hepatitis |date=24 July 2009 |publisher=U.S. Centers for Disease Control and Prevention (CDC) |access-date=22 October 2009|url-status=live|archive-url=https://web.archive.org/web/20091020015459/http://www.cdc.gov/hepatitis/index.htm|archive-date=20 October 2009}}

On 10 December 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 the medicinal product Heplisav{{nbsp}}B, intended for the active immunization against hepatitis{{nbsp}}B virus infection (HBV).{{cite web | title=Heplisav B: Pending EC decision | website=European Medicines Agency (EMA) | date=10 December 2020 | url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/heplisav-b | access-date=11 December 2020 | archive-date=11 December 2020 | archive-url=https://web.archive.org/web/20201211165159/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/heplisav-b | url-status=dead }} 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 Dynavax GmbH. It was approved for medical use in the European Union in February 2021.

On 24 February 2022, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product PreHevbri, intended for the active immunization against hepatitis B virus infection (HBV). The applicant for this medicinal product is VBI Vaccines B.V.{{cite web | title=PreHevbri: Pending EC decision | website=European Medicines Agency (EMA) | date=25 February 2022 | url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/prehevbri | access-date=27 February 2022 | archive-date=27 February 2022 | archive-url=https://web.archive.org/web/20220227043811/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/prehevbri | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. PreHevbri was approved for medical use in the European Union in April 2022.{{cite web | title=PreHevbri EPAR | website=European Medicines Agency (EMA) | date=22 February 2022 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/prehevbri | access-date=3 March 2023}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.{{cite web | title=PreHevbri Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1641.htm | access-date=3 March 2023}}

The common brands available are Recombivax HB (Merck),{{cite web | title=Recombivax HB | website=U.S. Food and Drug Administration (FDA) | date=24 April 2019 | url=https://www.fda.gov/vaccines-blood-biologics/vaccines/recombivax-hb | access-date=6 May 2020 | archive-date=11 February 2020 | archive-url=https://web.archive.org/web/20200211084714/https://www.fda.gov/vaccines-blood-biologics/vaccines/recombivax-hb | url-status=dead }} Engerix-B (GSK),{{cite web | title=Engerix-B | website=U.S. Food and Drug Administration (FDA) | date=3 October 2019 | url=https://www.fda.gov/vaccines-blood-biologics/vaccines/engerix-b | access-date=6 May 2020 | archive-date=11 February 2020 | archive-url=https://web.archive.org/web/20200211084654/https://www.fda.gov/vaccines-blood-biologics/vaccines/engerix-b | url-status=dead }} Elovac B (Human Biologicals Institute, a division of Indian Immunologicals Limited), Genevac B (Serum Institute), Shanvac B, Heplisav-B, Prehevbrio,{{cite web | title=PreHevbrio | website=U.S. Food and Drug Administration | date=13 December 2021 | url=https://www.fda.gov/vaccines-blood-biologics/prehevbrio | access-date=19 December 2021 | archive-date=19 December 2021 | archive-url=https://web.archive.org/web/20211219211400/https://www.fda.gov/vaccines-blood-biologics/prehevbrio | url-status=dead }} and Euvax B (LG Chem).{{cite web | title=Euvax B | website=WHO | date=28 November 2024 | archive-url=https://web.archive.org/web/20240727175359/https://extranet.who.int/prequal/vaccines/p/euvax-b-1 | archive-date=27 July 2024 | url=https://extranet.who.int/prequal/vaccines/p/euvax-b-1 | url-status=live}}

Twinrix (GSK) is a vaccine against hepatitis A and hepatitis B.{{cite web |title=Hepatitis A & hepatitis B recombinant vaccine – Drug Summary |url=https://www.pdr.net/drug-summary |website=www.pdr.net |publisher=Prescriber's Digital Reference |access-date=4 June 2019 |archive-date=4 June 2019 |archive-url=https://web.archive.org/web/20190604060328/https://www.pdr.net/drug-summary/Twinrix-hepatitis-A--amp--hepatitis-B--recombinant--vaccine-231 |url-status=live }}{{cite web | title=Twinrix | website=U.S. Food and Drug Administration (FDA) | url=https://www.fda.gov/vaccines-blood-biologics/vaccines/twinrix | access-date=22 September 2019 | archive-date=22 September 2019 | archive-url=https://web.archive.org/web/20190922202740/https://www.fda.gov/vaccines-blood-biologics/vaccines/twinrix | url-status=dead }}

Pediarix is a vaccine against diphtheria, tetanus, pertussis, hepatitis B, and poliomyelitis.{{cite web | title=Pediarix | website=U.S. Food and Drug Administration (FDA) | url=https://www.fda.gov/vaccines-blood-biologics/vaccines/pediarix | access-date=22 September 2019 | archive-date=22 September 2019 | archive-url=https://web.archive.org/web/20190922202657/https://www.fda.gov/vaccines-blood-biologics/vaccines/pediarix | url-status=dead }}

Vaxelis is a vaccine against diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus influenzae type B (Meningococcal Protein Conjugate), and hepatitis B.{{cite web|url=https://www.ema.europa.eu/en/medicines/human/EPAR/vaxelis|title=Vaxelis EPAR|access-date=16 October 2019|date=19 February 2019|website=European Medicines Agency (EMA)|archive-date=17 October 2019|archive-url=https://web.archive.org/web/20191017045354/https://www.ema.europa.eu/en/medicines/human/EPAR/vaxelis|url-status=live}}{{cite web | title=Vaxelis | website=U.S. Food and Drug Administration (FDA) | url=https://www.fda.gov/vaccines-blood-biologics/vaxelis | archive-url=https://web.archive.org/web/20191017044241/https://www.fda.gov/vaccines-blood-biologics/vaxelis | archive-date=17 October 2019 | url-status=dead | access-date=16 October 2019 |id=STN 125563}}

Fendrix (hepatitis B (rDNA) vaccine (adjuvanted, adsorbed)) was approved for medical use in the European Union in 2005.{{cite web | title=Fendrix EPAR | website=European Medicines Agency (EMA) | date=2 February 2005 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/fendrix | access-date=27 December 2023}}

{{Reflist}}

• {{cite book | title=Immunisation Against Infectious Disease | chapter=Chapter 18: Hepatitis B | chapter-url=https://www.gov.uk/government/publications/hepatitis-b-the-green-book-chapter-18 | publisher=Public Health England | veditors = Ramsay M | url=https://www.gov.uk/government/collections/immunisation-against-infectious-disease-the-green-book | year=2019 }}
• {{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 10: Hepatitis B | chapter-url = https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-10-hepatitis-b.html | url=https://www.cdc.gov/pinkbook/hcp/table-of-contents/ }}

{{Commons category}}

• {{cite web | title=Hepatitis B Vaccine Information Statement | date=25 September 2024 | publisher=U.S. Centers for Disease Control and Prevention (CDC) | url=https://www.cdc.gov/vaccines/hcp/vis/vis-statements/hep-b.html }}
• {{MeshName|Hepatitis B Vaccines}}

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