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{{Short description|Vaccine against hepatitis B}}
{{Drugbox
{{Use dmy dates|date=November 2022}}
| verifiedrevid = 446097372
{{cs1 config|name-list-style=vanc|display-authors=6}}
| image =
{{Infobox drug
| drug_name = Hepatitis B vaccine
| Verifiedfields = changed

| verifiedrevid = 447912967
<!--Vacine data-->
| type = vaccine | type = vaccine
| target = ] | image = Engerix B (Hepatitis B) vaccine.jpg
| width =
| alt =
| caption = Hepatitis B vaccine

<!-- Vacine data -->
| target = ] virus
| vaccine_type = subunit | vaccine_type = subunit


<!--Clinical data--> <!-- Clinical data -->
| tradename = | pronounce =
| tradename = Recombivax HB, Engerix-B, Heplisav-B, others
| Drugs.com = {{drugs.com|monograph|hepatitis_b_vaccine}} | Drugs.com = {{drugs.com|monograph|hepatitis_b_vaccine}}
| MedlinePlus = a607014 | MedlinePlus = a607014
| DailyMedID = Hepatitis B vaccine
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_AU = B2
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_AU_comment = <ref name="drugs.com pregnancy">{{cite web | title=Hepatitis b adult vaccine Pregnancy and Breastfeeding Warnings | website=Drugs.com | date=27 April 2020 | url=https://www.drugs.com/pregnancy/hepatitis-b-adult-vaccine.html | access-date=19 December 2021 | archive-date=27 October 2020 | archive-url=https://web.archive.org/web/20201027035336/https://www.drugs.com/pregnancy/hepatitis-b-adult-vaccine.html | url-status=live }}</ref>
| pregnancy_category =
| pregnancy_category =
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
| routes_of_administration = ] (IM)
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| class = ]
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| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_status =
| routes_of_administration =

<!--Identifiers-->
| CAS_number =
| ATC_prefix = J07 | ATC_prefix = J07
| ATC_suffix = BC01 | ATC_suffix = BC01
| ATC_supplemental =
| PubChem =

<!-- Legal status -->
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->
| legal_AU_comment =
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| legal_BR_comment =
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| legal_CA_comment =
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = POM
| legal_UK_comment = <ref>{{cite web | url=https://www.medicines.org.uk/emc/product/1684/smpc | title=Engerix B SmPC | date=24 April 2017 | publisher=Datapharm | access-date=22 September 2019 | archive-date=22 September 2019 | archive-url=https://web.archive.org/web/20190922194519/https://www.medicines.org.uk/emc/product/1684/smpc | url-status=live }}</ref><ref>{{cite web | url=https://www.medicines.org.uk/emc/product/1684/smpc | title=HBVaxPro SmPC | date=12 March 2019 | publisher=Datapharm | access-date=22 September 2019 | archive-date=22 September 2019 | archive-url=https://web.archive.org/web/20190922194519/https://www.medicines.org.uk/emc/product/1684/smpc | url-status=live }}</ref>
| legal_US = Rx-only
| legal_US_comment = <ref name="FDA Heplisav" /><ref name="FDA Recombivax HB" /><ref name="FDA Engerix-B" /><ref name="FDA PreHevbrio" /><ref>{{cite web | title=Hepatitis B Vaccine Monograph for Professionals | website=Drugs.com | date=1 September 2019 | url=https://www.drugs.com/monograph/hepatitis-b-vaccine.html | access-date=19 December 2019 | archive-date=21 October 2019 | archive-url=https://web.archive.org/web/20191021093504/https://www.drugs.com/monograph/hepatitis-b-vaccine.html | url-status=live }}</ref>
| legal_EU = Rx-only
| legal_EU_comment = <ref name="Heplisav B EPAR">{{cite web | title=Heplisav B EPAR | website=] (EMA) | date=9 December 2020 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/heplisav-b | access-date=1 March 2021 | archive-date=8 March 2021 | archive-url=https://web.archive.org/web/20210308000056/https://www.ema.europa.eu/en/medicines/human/EPAR/heplisav-b | url-status=live }}</ref><ref name="PreHevbri EPAR" /><ref>{{cite web | title=Heplisav B Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1503.htm | access-date=3 March 2023}}</ref><ref name="PreHevbri EU approval" />
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment =
| legal_status = Rx-only

<!-- Identifiers -->
| CAS_number_Ref =
| CAS_number =
| CAS_supplemental =
| PubChem = 16131310
| IUPHAR_ligand =
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = | DrugBank = DB11627
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = none
| UNII_Ref =
| UNII = IFJ010MNE4
| UNII2 = XL4HLC6JH6
| KEGG_Ref =
| KEGG = D04432
| ChEBI_Ref =
| ChEBI =
| ChEMBL_Ref =
| ChEMBL =
| NIAID_ChemDB =
| PDB_ligand =
| synonyms =


<!--Chemical data--> <!-- Chemical and physical data -->
}} }}


<!-- Definition and medical uses -->
'''Hepatitis B vaccine''' is a ] developed for the prevention of ]. The vaccine contains one of the viral envelope ], hepatitis B surface antigen (]). It is produced by yeast cells, into which the genetic code for HBsAg has been inserted.<ref>{{Cite web|url=http://www.rxlist.com/recombivax-drug.htm|title=Hepatitis B Vaccine from Merck|accessdate=2010-05-09}}</ref> A course of three (3) vaccine injections are given with the second injection at least one month after the first dose and the third injection given six months after the first dose.<ref>{{Cite web|url=http://www.hepb.org/hepb/vaccine_information.htm|title=Hepatitis B Vaccine|date=2009-01-31|publisher=Hepatitis B Foundation|location=Doylestown, Pennsylvania|accessdate=2009-10-22}}</ref> Afterward an immune system ] to HBsAg is established in the bloodstream. The antibody is known as ''anti-HBsAg''. This antibody and immune system memory then provide immunity to hepatitis B infection.<ref>{{Cite web|url=http://www.cdc.gov/hepatitis/index.htm|title=CDC Viral Hepatitis|date=2009-07-24|publisher=Centers for Disease Control and Prevention|location=Atlanta, Georgia|accessdate=2009-10-22}}</ref> The first vaccine became available in 1981.
'''Hepatitis B vaccine''' is a ] that prevents ].<ref name=WHO2017>{{cite journal |vauthors=((World Health Organization)) |title=Hepatitis B vaccines: WHO position paper – July 2017 |journal=Wkly. Epidemiol. Rec. |volume=92 |issue=27 |pages=369–92 |date=July 2017 |pmid=28685564 |author-link = World Health Organization |hdl=10665/255873 | hdl-access=free | url=https://iris.who.int/bitstream/handle/10665/255873/WER9227-369-392.pdf?sequence=1&isAllowed=y<!--direct link to pdf.--> }}</ref> The first dose is recommended within 24 hours of birth with either two or three more doses given after that.<ref name=WHO2017/> This includes those with ] such as from ] and those born ].<ref name=WHO2017/> It is also recommended that health-care workers be vaccinated.<ref name=Chen2005>{{cite journal | vauthors = Chen W, Gluud C | title = Vaccines for preventing hepatitis B in health-care workers | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD000100 | date = October 2005 | pmid = 16235273 | doi = 10.1002/14651858.CD000100.pub3 }}</ref> In healthy people, routine immunization results in more than 95% of people being protected.<ref name=WHO2017/>


<!-- Administration -->
A range of vaccines are available in the market. Presently recombinant DNA vaccines are available, which means they are produced by inserting the gene for HBV into common baker's yeast where it is grown, harvested, and purified. HBV infection cannot occur from receiving hepatitis B vaccine. The common brands available are Engerix-B (GSK), Elovac B (Human Biologicals Institute, A division of Indian Immunologicals Limited), Genevac B (Serum Institute), Shanvac B etc. These vaccines are given intramuscularly.
Blood testing to verify that the vaccine has worked is recommended in those at high risk.<ref name=WHO2017/> Additional doses may be needed in people with poor immune function but are not necessary for most people.<ref name=WHO2017/> In those who have been exposed to the ] (HBV) but not immunized, ] should be given in addition to the vaccine.<ref name=WHO2017/> The vaccine is given by ].<ref name=WHO2017/>


<!-- Safety and formulation -->
==The invention==
Serious side effects from the hepatitis B vaccine are very uncommon.<ref name=WHO2017/> Pain may occur at the site of injection.<ref name=WHO2017/> It is safe for use during ] or while ].<ref name=WHO2017/> It has not been linked to ].<ref name=WHO2017/> Hepatitis B vaccines are produced with ] techniques and contain ].<ref name=WHO2017/> They are available both by themselves and in combination with other vaccines.<ref name=WHO2017/>
The invention of the vaccine began with the realization (by virologist Alfred Prince, in 1968) that the ] was part of a virus that caused hepatitis. ] at ] used three treatments (], ] and ]) of blood serum together with rigorous filtration to yield a product that could be used as a safe vaccine. This was first licensed by the FDA in 1981. It was not very successful in the marketplace because clinicians knew that it was a product made from human blood serum. It was withdrawn from the marketplace when ], Research Director of ] succeeded in 1986 in making the antigen in yeast and invented the first recombinant vaccine <ref> The New York Times </ref>. This is the vaccine still in use today.


<!-- History, society and culture -->
==Recommended populations==
The first hepatitis B vaccine was approved in the United States in 1981.<ref>{{cite book| vauthors = Moticka E |title=A Historical Perspective on Evidence-Based Immunology|isbn=9780123983756|page=336|url=https://books.google.com/books?id=2TMwAAAAQBAJ&pg=PA336|date=25 November 2015 |publisher=Newnes }}</ref> A recombinant version came to market in 1986.<ref name=WHO2017/> It is on the ].<ref name="WHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref> Both versions were developed by ] and his team.<ref name=":0">{{cite journal | vauthors = Tulchinsky TH | title = Maurice Hilleman: Creator of Vaccines That Changed the World. | journal = Case Studies in Public Health | pages = 443–470 | date = 2018 | pmc = 7150172 | doi = 10.1016/B978-0-12-804571-8.00003-2 | isbn = 9780128045718 }}</ref><ref>{{cite journal | vauthors = Oransky I | title = Maurice R. Hilleman | language = English | journal = Lancet | volume = 365 | issue = 9472 | pages = 1682 | date = 14 May 2005 | pmid = 15912596 | doi = 10.1016/S0140-6736(05)66536-1 | s2cid = 46630955 }}</ref><ref name=":2">{{Cite book| vauthors = Offit PA |url= https://vaccinemakers.org/sites/default/files/resources/HS.reading%20passage-Blood.unit2_.lesson4.FINAL_.pdf|title=Vaccinated: One Man's Quest to Defeat the World's Deadliest Diseases|publisher=]|year=2007|isbn=|location=|pages=115–126, 136–140|chapter=Chapter 8: Blood|access-date=9 January 2021|archive-date=5 October 2021|archive-url=https://web.archive.org/web/20211005095630/https://vaccinemakers.org/sites/default/files/resources/HS.reading%20passage-Blood.unit2_.lesson4.FINAL_.pdf|url-status=live}}</ref>


==Medical uses==
Babies born to mothers with active hepatitis B infections are recommended to receive treatment reducing the risk of mother-to-child transmission of the hepatitis B infection. As soon as possible and within 48 hours of birth, newborns are vaccinated with hepatitis B surface antigen (HBsAg) and injected with hepatitis B immunoglobulin (HBIG).<ref name="pmid16371945">{{Cite pmid|16371945}}</ref>
In the United States vaccination is recommended for nearly all babies at birth.<ref>{{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 }}</ref> 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 ]. This was reported in ] where the implementation of a nationwide hepatitis B vaccination program in 1984 was associated with a decline in the incidence of childhood ].<ref name=Chang_1997>{{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 }}</ref>


In the UK, the vaccine is offered to ] (MSM), usually as part of a sexual health check-up. A similar situation is in operation in Ireland.<ref>{{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}}</ref>
Many countries now 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 marked reduction in ]. This was reported in ] where the implementation of a nationwide hepatitis B vaccination program in 1984 was associated with a decline in the incidence of childhood hepatocellular carcinoma.<ref name=Chang_1997>{{cite doi|10.1056/NEJM199706263362602}}</ref>


In many areas, vaccination against hepatitis B is also required for all health-care and laboratory staff.<ref name="isbn0113225288-c12">{{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|chapterurl=http://www.dh.gov.uk/en/Publichealth/Healthprotection/Immunisation/Greenbook/DH_4097254?IdcService=GET_FILE&dID=115800&Rendition=Web|format=PDF|publisher=Stationery Office|location=Edinburgh|year=2006|pages=468|isbn=0113225288|oclc=|doi=}}</ref> In many areas, vaccination against hepatitis B is also required for all health-care and laboratory staff.<ref name="isbn0113225288-c12">{{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}}</ref> Both types of the vaccine, the plasma-derived vaccine (PDV) and ] (RV), seems to be able to elicit similar protective anti-HBs levels.<ref name=Chen2005 />


The US ] (CDC) issued recommendations for vaccination against hepatitis B among patients with ].<ref name="pmid22189894">{{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. ] (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 }}</ref> The ] (WHO) recommends a ], combining vaccines against ], ], ] and ] 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.<ref>{{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 }}</ref> A pentavalent vaccine combining vaccines against diphtheria, tetanus, pertussis, hepatitis B, and ]myelitis is approved in the U.S. and is recommended by the ] (ACIP).<ref>{{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. ] (CDC) }}</ref><ref>{{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. ] (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 }}</ref><ref>{{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 }}</ref>
An Australian couple in August 2008 went on the run after the New South Wales Supreme Court extended an order forcing them to immunise their newborn against the disease. DOCS (Department of Community Services) took out the order, as doctors say the five-day-old baby is at a high risk of contracting the illness as his mother has the disease. The parents believe (see ]) that aluminium in the vaccine would cause the baby more harm than the disease itself.<ref>{{Cite news|title=Evidence supports action against 'hep B' baby's parents: DOCS|url=http://www.abc.net.au/news/stories/2008/08/25/2346031.htm|publisher=ABC News|location=Sydney, Australia|date=2008-08-25|accessdate=2009-10-22}}</ref><ref>{{Cite news|title=Court extends order for 'hep B' baby|url=http://www.abc.net.au/news/stories/2008/08/25/2345782.htm|publisher=ABC News|location=Croydon Park, Australia|date=2008-08-25|accessdate=2009-10-22}}</ref>


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 ] (HBV).<ref name=":1">{{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}}</ref> The combination is superior for protecting these infants.<ref name=":1" /> The effectiveness of being vaccinated during pregnancy to prevent ] of hepatitis B to infants has not been studied.<ref name="pmid25385500">{{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}}</ref> Hepatitis B immunoglobulin before birth has not been well studied.<ref name="pmid28188612">{{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}}</ref>
==Response to vaccination==


===Effectiveness===
Following the primary course of 3 vaccinations, a blood test may be taken after an interval of 1&ndash;4 months to establish if there has been an adequate response, which is defined as an ] (anti-Hbs) antibody level above 100 mIU/ml. Such a full response occurs in about 85-90% of individuals.<ref name="isbn0113225288 " />
Studies have found that that ] 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-Hbs) levels decline below detectable levels.<ref name="ImmunizeHepB">{{cite web |title=Ask the Experts: Hepatitis B |url=https://www.immunize.org/askexperts/experts_hepb.asp |website=Immunize.org |publisher=] |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 }}</ref> 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 ]d people such as ] patients, ] patients, ] recipients, or people receiving ]; and for sexual partners of HBsAg-positive people.<ref name="ImmunizeHepB"/>


An anti-Hbs antibody level above 100{{nbsp}}]/ml is deemed adequate and occurs in about 85–90% of individuals.<ref name="isbn0113225288 " /> 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.<ref name="isbn0113225288 " /> 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 ]<ref name="Filippelli2014"/> or to a high dose vaccine<ref>{{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 }}</ref> or to a double dose of a combined ] and B vaccine.<ref>{{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 }}</ref> Those who still fail to respond will require hepatitis B ] (HBIG) if later exposed to the hepatitis B virus.<ref name="isbn0113225288" />
An antibody level between 10 and 100 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.<ref name="isbn0113225288 " />


Poor responses are mostly associated with being over the age of 40 years, ], ], and ],<ref name="Filippelli2014">{{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 }}</ref><ref name="pmid8254852">{{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 }}</ref> and also in ], especially if with ].<ref name="pmid9316554">{{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 }}</ref> People who are immunosuppressed or on ] may not respond as well and require larger or more frequent doses of vaccine.<ref name="isbn0113225288" /> At least one study suggests that hepatitis B vaccination is less effective in patients with ].<ref>{{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 </ref> The immune response to the hepatitis B vaccine can be impaired by the presence of parasitic infections such as ].<ref>{{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 }}</ref>
People who fail to respond (anti-Hbs antibody level below 10 mIU/ml) should be tested to exclude current or past Hepatitis B infection, and given a repeat course of 3 vaccinations, followed by further retesting 1&ndash;4 months after the second course. Those who still do not respond to a second course of vaccination may respond to intradermal administration<ref>{{cite pmid|2148433}}</ref> or to a high dose vaccine <ref>{{Cite pmid|7759824}}</ref> or to a double dose of a combined Hepatitis A and B vaccine.<ref>{{Cite pmid|18544037}}</ref> Those who still fail to respond will require hepatitis B ] (HBIG) if later exposed to the hepatitis B virus.<ref name="isbn0113225288" />


===Duration of protection===
Poor responses are mostly associated with being over the age of 40 years, obesity and smoking,<ref name="pmid8254852">{{cite doi|10.1001/jama.270.24.2931}}</ref> and also in alcoholics, especially if with advanced liver disease.<ref name="pmid9316554">{{Cite doi|10.1016/S0002-9343(97)00132-0}}</ref> Patients who are immunosuppressed or on renal dialysis may respond less well and require larger or more frequent doses of vaccine.<ref name="isbn0113225288" /> At least one study suggests that hepatitis B vaccination is less effective in patients with HIV.<ref>{{cite doi|10.1186/1471-2334-6-65}}</ref>
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,<ref>{{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 }}</ref><ref>{{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 }}</ref> but immune-challenge studies show that even after 30 years, the immune system maintains the ability to produce an ], i.e. to rapidly bump up antibody levels when the previously seen antigen is detected.<ref name="pmid17298912">{{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 }}</ref><ref>{{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 }}</ref> This shows that the ] 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.<ref name="pmid17291637">{{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 }}</ref><ref name="pmid10683019">{{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 }}</ref> 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.<ref name="isbn0113225288 ">{{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}}</ref>


==Side effects==
==Duration of protection==
Serious side effects from the hepatitis B vaccine are very rare.<ref name=WHO2017/> Pain may occur at the site of injection.<ref name=WHO2017/> It is generally considered safe for use, during ] or while ].<ref name=WHO2017/><ref>{{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 }}</ref> It has not been linked to ].<ref name=WHO2017/>


===Multiple sclerosis===
It is now believed that the hepatitis B vaccine provides indefinite protection. However, it was previously believed and suggested that the vaccination would only provide effective cover of between five and seven years,<ref>{{Cite pmid|3660859}}</ref><ref>{{Cite doi|10.1097/01.inf.0000130952.96259.fd}}</ref> but subsequently it has been appreciated that long-term immunity derives from immunological memory which outlasts the loss of antibody levels and hence subsequent testing and administration of booster doses is not required in successfully vaccinated immunocompetent individuals.<ref name="pmid17291637">{{Cite doi|10.1016/j.vaccine.2007.01.045}}</ref><ref name="pmid10683019">{{cite doi|10.1016/S0140-6736(99)07239-6}}</ref> Hence with the passage of time and longer experience, protection has been shown for at least 25 years in those who showed an adequate initial response to the primary course of vaccinations,<ref name="pmid17298912">{{Cite doi|10.1016/j.tmaid.2006.04.004}}</ref> and UK guidelines now suggest that for initial responders who require ongoing protection, such as for healthcare workers, only a single booster is advocated at 5 years.<ref name="isbn0113225288 ">{{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|chapterurl=http://www.dh.gov.uk/en/Publichealth/Healthprotection/Immunisation/Greenbook/DH_4097254?IdcService=GET_FILE&dID=152019&Rendition=Web|format=PDF|publisher=Stationery Office|location=Edinburgh|year=2006|pages=468|isbn=0113225288}}</ref>
Several studies have looked for an association between recombinant hepatitis B vaccine and ] (MS) in adults.<ref name=Mar2013>{{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 }}</ref> Most studies do not support a causal relationship between hepatitis B vaccination and demyelinating diseases such as MS.<ref name=Mar2013/><ref name=CDCFAQ>{{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. ] (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}}</ref><ref name="Mouchet2018">{{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}}</ref> A 2004 study reported a significant increase in risk within three years of vaccination. Some of these studies were criticized for methodological problems.<ref>{{cite journal | vauthors = ], 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 }}</ref> 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 ], ], or multiple sclerosis.<ref>{{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 }}</ref> A 2007 study found that the vaccination does not seem to increase the risk of a first episode of MS in childhood.<ref>{{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 }}</ref> Hepatitis B vaccination has not been linked to onset of autoimmune diseases in adulthood.<ref name="Elwood2018">{{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}}</ref>


==Safety== ==Usage==
]
Several studies looked for a significant association between recombinant hepatitis B vaccine (HBV) and ] (MS) in adults. Most published scientific studies do not support a causal relationship between hepatitis B vaccination and demyelinating diseases such as MS.<ref name=CDCFAQ>, ]</ref> A 2004 study<ref>{{cite pmid|15365133}}</ref> reported a significant increase in risk within 3 years of vaccination. Some of these studies were criticized for methodological problems. This controversy created public misgivings about HB vaccination, and hepatitis B vaccination in children remained low in several countries. A 2007 study found that the vaccination does not seem to increase the risk of a first episode of MS in childhood.<ref>{{cite doi|10.1001/archpedi.161.12.1176}}</ref>


The following is a list of countries by the percentage of infants receiving three doses of hepatitis B vaccine as published by the ] (WHO) in 2017.<ref>{{cite web|title=Hepatitis B (HepB3) Immunization coverage estimates by country|url=http://apps.who.int/gho/data/node.main.A828?lang=en|website=WHO|access-date=8 June 2016|archive-date=11 May 2016|archive-url=https://web.archive.org/web/20160511165405/http://apps.who.int/gho/data/node.main.A828?lang=en|url-status=live}}</ref>
A 2009 study of the hepatitis B vaccine and associated risk of CNS inflammatory ] was conducted. The hepatitis B vaccine was found to be generally safe, however the Engerix B vaccine appeared to triple the risk of CNS inflammatory demyelination in infant boys.<ref>{{Cite web|url=http://www.neurology.org/cgi/content/abstract/72/10/873|title=Hepatitis B vaccine and the risk of CNS inflammatory demyelination in childhood|year=2009|publisher=Neurology}}</ref> There have been numerous reports that the Hepatitis B vaccine is linked to ], a syndrome marked by severe fatigue, brain fogs, and muscle pains among other symptoms. <ref>{{cite web|last=Lanctot MD|first=Guylaine|title=Association of American Physicians&Surgeons Report|url=http://vran.org/vaccines/hepatitis/cfs.htm|work=Association of American Physicians&Surgeons Report|publisher=VRAN|accessdate=11 March 2011}}</ref>
The Engerix B vaccine contained ], a mercury containing vaccine preservative that is being phased out at the urging of the Public Health Service in the US.<ref>{{Cite web|url=http://www.fda.gov/biologicsbloodvaccines/safetyavailability/vaccinesafety/ucm096228.htm|title=Thiomersal in Vaccines|date=2010-03-31|publisher=U.S. Food and Drug Administration}}</ref>


{| class="wikitable sortable mw-collapsible mw-collapsed"
==References==
|-
! colspan=2 | Hepatitis B (HepB3) immunization coverage<br />among one-year-olds worldwide
|-
! scope="col" | Country
! scope="col" | Coverage %
|-
|Afghanistan ||65
|-
|Albania ||99
|-
|Algeria ||91
|-
|Andorra ||98
|-
|Angola ||52
|-
|Antigua and Barbuda ||95
|-
|Argentina ||86
|-
|Armenia ||94
|-
|Australia ||95
|-
|Austria ||90
|-
|Azerbaijan ||95
|-
|Bahamas ||94
|-
|Bahrain ||98
|-
|Bangladesh ||97
|-
|Barbados ||90
|-
|Belarus ||98
|-
|Belgium ||97
|-
|Belize ||88
|-
|Benin ||82
|-
|Bhutan ||98
|-
|Bolivia (Plurinational State of) ||83
|-
|Bosnia and Herzegovina ||77
|-
|Botswana ||95
|-
|Brazil ||93
|-
|Brunei Darussalam ||99
|-
|Bulgaria ||92
|-
|Burkina Faso ||91
|-
|Burundi ||91
|-
|Côte d'Ivoire ||84
|-
|Cabo Verde ||86
|-
|Cambodia ||93
|-
|Cameroon ||86
|-
|Canada ||69
|-
|Central African Republic ||47
|-
|Chad ||41
|-
|Chile ||93
|-
|China ||99
|-
|Colombia ||92
|-
|Comoros ||91
|-
|Congo ||69
|-
|Cook Islands ||99
|-
|Costa Rica ||97
|-
|Croatia ||94
|-
|Cuba ||99
|-
|Cyprus ||97
|-
|Czech Republic ||94
|-
|Democratic People's Republic of Korea ||97
|-
|Democratic Republic of the Congo ||81
|-
|Djibouti ||68
|-
|Dominica ||91
|-
|Dominican Republic ||81
|-
|Ecuador ||84
|-
|Egypt ||94
|-
|El Salvador ||85
|-
|Equatorial Guinea ||25
|-
|Eritrea ||95
|-
|Estonia ||92
|-
|Eswatini || 90
|-
|Ethiopia ||73
|-
|Fiji ||99
|-
|France ||90
|-
|Gabon ||75
|-
|Gambia ||92
|-
|Georgia ||91
|-
|Germany ||87
|-
|Ghana ||99
|-
|Greece ||96
|-
|Grenada ||96
|-
|Guatemala ||82
|-
|Guinea ||45
|-
|Guinea-Bissau ||87
|-
|Guyana ||97
|-
|Haiti ||58
|-
|Honduras ||97
|-
|India ||88
|-
|Indonesia ||79
|-
|Iran (Islamic Republic of) ||99
|-
|Iraq ||63
|-
|Ireland ||95
|-
|Israel ||97
|-
|Italy ||94
|-
|Jamaica ||93
|-
|Jordan ||99
|-
|Kazakhstan ||99
|-
|Kenya ||82
|-
|Kiribati ||90
|-
|Kuwait ||99
|-
|Kyrgyzstan ||92
|-
|Lao People's Democratic Republic ||85
|-
|Latvia ||98
|-
|Lebanon ||78
|-
|Lesotho ||93
|-
|Liberia ||86
|-
|Libya ||94
|-
|Lithuania ||94
|-
|Luxembourg ||94
|-
|Macedonia ||91
|-
|Madagascar ||74
|-
|Malawi ||88
|-
|Malaysia ||98
|-
|Maldives ||99
|-
|Mali ||66
|-
|Malta ||88
|-
|Marshall Islands ||82
|-
|Mauritania ||81
|-
|Mauritius ||96
|-
|Mexico ||93
|-
|Micronesia (Federated States of) ||80
|-
|Monaco ||99
|-
|Mongolia ||99
|-
|Montenegro ||73
|-
|Morocco ||99
|-
|Mozambique ||80
|-
|Myanmar ||89
|-
|Namibia ||88
|-
|Nauru ||87
|-
|Nepal ||90
|-
|Netherlands ||92
|-
|New Zealand ||94
|-
|Nicaragua ||98
|-
|Niger ||81
|-
|Nigeria ||42
|-
|Niue ||99
|-
|Oman ||99
|-
|Pakistan ||75
|-
|Palau ||98
|-
|Panama ||81
|-
|Papua New Guinea ||56
|-
|Paraguay ||91
|-
|Peru ||83
|-
|Philippines ||88
|-
|Poland ||95
|-
|Portugal ||98
|-
|Qatar ||97
|-
|Republic of Korea ||98
|-
|Republic of Moldova ||89
|-
|Romania ||92
|-
|Russian Federation ||97
|-
|Rwanda ||98
|-
|Saint Kitts and Nevis ||98
|-
|Saint Lucia ||80
|-
|Saint Vincent and the Grenadines ||99
|-
|Samoa ||73
|-
|San Marino ||86
|-
|São Tomé and Príncipe ||95
|-
|Saudi Arabia ||98
|-
|Senegal ||91
|-
|Serbia ||93
|-
|Seychelles ||98
|-
|Sierra Leone ||90
|-
|Singapore ||96
|-
|Slovakia ||96
|-
|Solomon Islands ||99
|-
|Somalia ||42
|-
|South Africa ||66
|-
|Spain ||93
|-
|Sri Lanka ||99
|-
|Sudan ||95
|-
|Suriname ||81
|-
|Swaziland ||98
|-
|Sweden ||76
|-
|Syrian Arab Republic ||52
|-
|Tajikistan ||96
|-
|Thailand ||99
|-
|Timor-Leste ||76
|-
|Togo ||90
|-
|Tonga ||81
|-
|Trinidad and Tobago ||89
|-
|Tunisia ||98
|-
|Turkey ||96
|-
|Turkmenistan ||99
|-
|Tuvalu ||96
|-
|Uganda ||85
|-
|Ukraine ||52
|-
|United Arab Emirates ||98
|-
|United Republic of Tanzania ||97
|-
|United States of America ||93
|-
|Uruguay ||95
|-
|Uzbekistan ||99
|-
|Vanuatu ||85
|-
|Venezuela (Bolivarian Republic of) ||84
|-
|Viet Nam ||94
|-
|Yemen ||68
|-
|Zambia ||94
|-
|Zimbabwe ||89
|}


==History==
{{reflist|colwidth=30em}}


=== Preliminary work ===
{{Vaccines}}
In 1963, the American physician/geneticist ], working at the ], discovered what he called the "Australia Antigen" (]) in the serum of an ]n ].<ref name="pmid14239025">{{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 }}</ref> In 1968, this protein was found to be part of the virus that causes "serum hepatitis" (hepatitis B) by ] ].<ref name="isbn0-12-782150-3">{{cite book |author1=Howard, Colin |author2=Zuckerman, Arie J. |title=Hepatitis viruses of man |publisher=Academic Press |location=Boston |year=1979 |pages= |isbn=978-0-12-782150-4 |url=https://archive.org/details/hepatitisviruses0000zuck/page/16 }}</ref>
{{genetic engineering}}

In 1976, Blumberg won the ] for his work on hepatitis B (sharing it with ] for his work on ]).<ref>{{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}}</ref> 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 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''.<ref>Blumberg, Baruch (2002), ''Hepatitis B: The Hunt for a Killer Virus'', Princeton: Princeton University Press.</ref> 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 ], which had considerable experience with vaccines."

=== Blood-derived vaccine ===
During the next few years, a series of human and primate observations by scientists including ] (who was responsible for vaccines at Merck), ], 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 ] used three treatments (], ] and ]) 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.<ref name="PPAA">{{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 &#124; 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 }}</ref>

Hilleman collected blood from gay men and ]—groups known to be at risk for ]. 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.<ref name="PPAA"/>

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 ]) 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.<ref name="PPAA"/> The vaccine was approved in 1981.<ref name=":0" />

=== Recombinant vaccine ===
The blood-derived hepatitis B vaccine was withdrawn from the marketplace in 1986, replaced by ]'s improved recombinant hepatitis B vaccine which was approved by the ] on 23 July 1986.<ref name=":0" /><ref name=":2" /><ref name=":3">{{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}}</ref> It was the first human vaccine produced by recombinant DNA methods.<ref name=":3" /> For this work, scientists at ] collaborated with ] and colleagues at the ], as well as Benjamin Hall and colleagues at the ].<ref name=":4">{{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=]}}</ref> In 1981, William J. Rutter, ] and Edward Penhoet (]) co-founded the ] in ], which collaborated with Merck.<ref name=":4" /><ref>{{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}}</ref>

The recombinant vaccine is based on a Hepatitis B surface antigen (]) gene inserted into ] ('']'') cells which are free of any concerns associated with human blood products.<ref name=":0" /><ref name=":5" /> This allows the yeast to produce only the noninfectious surface protein, without any danger of introducing actual viral DNA into the final product.<ref name="PPAA" /> The vaccine contains the ] amorphous aluminum hydroxyphosphate sulfate.<ref name=":5" />

In 2017, a two-dose HBV vaccine for adults, Heplisav-B gained U.S. ] (FDA) approval.<ref name="FDA Heplisav">{{cite web | title=Heplisav-B | website=U.S. ] (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=live }}</ref> 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.<ref>{{cite web |author1=Dynavax Technologies Corp |title=Heplisav-B label |url=https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM584762.pdf |website=U.S. ] (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=live }}</ref>

In November 2021, Hepatitis B Vaccine (Recombinant) (Prehevbrio) was approved by the FDA.<ref name="FDA PreHevbrio" /><ref>{{cite web | title=ACIP Evidence to Recommendations for use of PreHevbrio Hepatitis B (HepB) Vaccine in Adults | publisher=U.S. ] (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 }}</ref><ref>{{cite web | title=Grading of Recommendations Assessment, Development and Evaluation (GRADE): PreHevbrio for Adults | publisher=U.S. ] (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 }}</ref><ref>{{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 }}</ref>

=== Immunization schedule ===
The US CDC ] first recommended the vaccine for all newborns in 1991.<ref>{{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=] |date=22 November 1991|volume=40 |issue=RR-13 |pages=1–19 |pmid=1835756 |access-date=15 May 2023}}</ref> 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.

==Manufacture==
The vaccine contains one of the viral envelope ], Hepatitis B surface antigen (]). It is produced by yeast cells, into which the gene for HBsAg has been inserted.<ref name=":5">{{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 }}</ref> Afterward an immune system ] 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.<ref>{{cite web |url=https://www.cdc.gov/hepatitis/index.htm |title=CDC Viral Hepatitis |date=24 July 2009 |publisher=U.S. ] (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}}</ref>

== Society and culture ==
=== Legal status ===
On 10 December 2020, the ] (CHMP) of the ] (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).<ref name="Heplisav B: Pending EC decision">{{cite web | title=Heplisav B: Pending EC decision | website=] (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.</ref> The applicant for this medicinal product is Dynavax GmbH.<ref name="Heplisav B: Pending EC decision" /> It was approved for medical use in the European Union in February 2021.<ref name="Heplisav B EPAR" />

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).<ref name="PreHevbri: Pending EC decision" /> The applicant for this medicinal product is VBI Vaccines B.V.<ref name="PreHevbri: Pending EC decision">{{cite web | title=PreHevbri: Pending EC decision | website=] (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.</ref> PreHevbri was approved for medical use in the European Union in April 2022.<ref name="PreHevbri EPAR">{{cite web | title=PreHevbri EPAR | website=] (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.</ref><ref name="PreHevbri EU approval">{{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}}</ref>

=== Brand names ===
The common brands available are Recombivax HB (]),<ref name="FDA Recombivax HB">{{cite web | title=Recombivax HB | website=U.S. ] (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=live }}</ref> Engerix-B (]),<ref name="FDA Engerix-B">{{cite web | title=Engerix-B | website=U.S. ] (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=live }}</ref> Elovac B (Human Biologicals Institute, a division of ]), Genevac B (]), Shanvac B, Heplisav-B,<ref name="FDA Heplisav" /><ref name="Heplisav B EPAR" /> Prehevbrio,<ref name="FDA 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=live }}</ref> and Euvax B (LG Chem).<ref name="Euvax B">{{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}}</ref>

] (]) is a vaccine against ] and hepatitis B.<ref>{{cite web |title=Hepatitis A & hepatitis B recombinant vaccine - Drug Summary |url=https://www.pdr.net/drug-summary/Twinrix-hepatitis-A--amp--hepatitis-B--recombinant--vaccine-231 |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 }}</ref><ref name="FDA Twinrix">{{cite web | title=Twinrix | website=U.S. ] (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=live }}</ref>

] is a vaccine against ], ], ], hepatitis B, and ]myelitis.<ref>{{cite web | title=Pediarix | website=U.S. ] (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=live }}</ref>

] is a vaccine against diphtheria, tetanus, pertussis, poliomyelitis, ] (Meningococcal Protein Conjugate), and hepatitis B.<ref>{{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=] (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}}</ref><ref>{{cite web | title=Vaxelis | website=U.S. ] (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=live | access-date=16 October 2019 |id=STN 125563}}</ref>

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

==References==
{{Reflist}}

== Further reading ==
* {{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. ] (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/ }}


==External links== ==External links==
{{Commons category}}
* {{cite web | title=Hepatitis B Vaccine Information Statement | date=25 September 2024 | publisher=U.S. ] (CDC) | url=https://www.cdc.gov/vaccines/hcp/vis/vis-statements/hep-b.html }}
* {{MeshName|Hepatitis B Vaccines}}


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{{Portal bar | Medicine | Viruses}}


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