_vaccine.jpg) Hepatitis B vaccine | |
| Vaccine description | |
|---|---|
| Target | Hepatitis B virus |
| Vaccine type | Subunit |
| Clinical data | |
| Trade names | Recombivax HB, Engerix-B, Heplisav-B, others |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a607014 |
| License data | |
| Pregnancy category | |
| Routes of administration | Intramuscular (IM) |
| Drug class | Antiviral |
| ATC code | |
| Legal status | |
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| Identifiers | |
| PubChemCID | |
| DrugBank |
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| ChemSpider |
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| KEGG | |
 N Y (what is this?) (verify) | |
Hepatitis B vaccine is avaccine that preventshepatitis B.[13] The first dose is recommended within 24 hours of birth with either two or three more doses given after that.[13] This includes those withpoor immune function such as fromHIV/AIDS and those bornpremature.[13] It is also recommended that health-care workers be vaccinated.[14] In healthy people, routine immunization results in more than 95% of people being protected.[13]
Blood testing to verify that the vaccine has worked is recommended in those at high risk.[13] Additional doses may be needed in people with poor immune function but are not necessary for most people.[13] In those who have been exposed to thehepatitis B virus (HBV) but not immunized,hepatitis B immune globulin should be given in addition to the vaccine.[13] The vaccine is given byinjection into a muscle.[13]
Serious side effects from the hepatitis B vaccine are very uncommon.[13] Pain may occur at the site of injection.[13] It is safe for use duringpregnancy or whilebreastfeeding.[13] It has not been linked toGuillain–Barré syndrome.[13] Hepatitis B vaccines are produced withrecombinant DNA techniques and containimmunologic adjuvant.[13] They are available both by themselves and in combination with other vaccines.[13]
The first hepatitis B vaccine (Merck's Heptavax-B) was approved in the United States in 1981.[15] A recombinant version (Merck's Recombivax-HB) came to market in 1986.[13] It is on theWorld Health Organization's List of Essential Medicines.[16] Both versions were developed byMaurice Hilleman and his team.[17][18][19]
In the United States vaccination is recommended for nearly all babies at birth.[20] 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 inliver cancer. This was reported inTaiwan where the implementation of a nationwide hepatitis B vaccination program in 1984 was associated with a decline in the incidence of childhoodhepatocellular carcinoma.[21]
In the UK, as well as being given to all babies at birth, the vaccine is also offered to people in various categories at higher risk, includingmen who have sex with men (MSM), usually as part of a sexual health check-up. A similar situation is in operation in Ireland.[22]
In many areas, vaccination against hepatitis B is also required for all health-care and laboratory staff.[23] Both types of the vaccine, the plasma-derived vaccine (PDV) andrecombinant vaccine (RV), seems to be able to elicit similar protective anti-HBs levels.[14]
The USCenters for Disease Control and Prevention (CDC) issued recommendations for vaccination against hepatitis B among patients withdiabetes mellitus.[24] TheWorld Health Organization (WHO) recommends apentavalent vaccine, combining vaccines againstdiphtheria,tetanus,pertussis andHaemophilus influenzae type B with the vaccine against hepatitis B.[medical citation needed] There is not yet sufficient evidence on how effective this pentavalent vaccine is compared to the individual vaccines.[25] A pentavalent vaccine combining vaccines against diphtheria, tetanus, pertussis, hepatitis B, andpoliomyelitis is approved in the U.S. and is recommended by theAdvisory Committee on Immunization Practices (ACIP).[26][27][28]
Hepatitis B vaccination, hepatitis B immunoglobulin, and the combination of hepatitis B vaccine plus hepatitis B immunoglobulin, are all considered as preventive for babies born to mothers infected withhepatitis B virus (HBV).[29] The combination is superior for protecting these infants.[29] The effectiveness of being vaccinated during pregnancy to preventvertical transmission of hepatitis B to infants has not been studied.[30] Hepatitis B immunoglobulin before birth has not been well studied.[31]
Studies have found that thatimmune memory against HepB is sustained for at least 30 years after vaccination, and protects against clinical disease and chronic HepB infection, even in cases whereanti-hepatitis B surface antigen (anti-Hbs) levels decline below detectable levels.[32] 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; forimmunocompromised people such ashaemodialysis patients,HIV patients,haematopoietic stem cell transplant [HSCT] recipients, or people receivingchemotherapy; and for sexual partners of HBsAg-positive people.[32]
An anti-Hbs antibody level above 100 mIU/ml is deemed adequate and occurs in about 85–90% of individuals.[33] 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.[33] 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 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 tointradermal injection[34] or to a high dose vaccine[35] or to a double dose of a combinedhepatitis A and B vaccine.[36] Those who still fail to respond will require hepatitis Bimmunoglobulin (HBIG) if later exposed to the hepatitis B virus.[33]
Poor responses are mostly associated with being over the age of 40 years,obesity,celiac disease, andtobacco smoking,[34][37] and also inalcoholics, especially if withadvanced liver disease.[38] People who are immunosuppressed or ondialysis may not respond as well and require larger or more frequent doses of vaccine.[33] At least one study suggests that hepatitis B vaccination is less effective in patients withHIV.[39] The immune response to the hepatitis B vaccine can be impaired by the presence of parasitic infections such ashelminthiasis.[40]
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.[41] These chronic HBV infections are life-threatening, with a 15–25% risk of death from complications.[41]
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,[42][43] but immune-challenge studies show that even after 30 years, the immune system maintains the ability to produce ananamnestic response, i.e. to rapidly bump up antibody levels when the previously seen antigen is detected.[44][45] This shows that theimmunological 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.[46][47] 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.[33]
Serious side effects from the hepatitis B vaccine are very rare.[13] Pain may occur at the site of injection.[13] It is generally considered safe for use, duringpregnancy or whilebreastfeeding.[13][48] It has not been linked toGuillain–Barré syndrome.[13]
Several studies have looked for an association between recombinant hepatitis B vaccine andmultiple sclerosis (MS) in adults.[49] Most studies do not support a causal relationship between hepatitis B vaccination and demyelinating diseases such as MS.[49][50][51] A 2004 study reported a significant increase in risk within three years of vaccination. Some of these studies were criticized for methodological problems.[52] 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 andsudden infant death syndrome,chronic fatigue syndrome, or multiple sclerosis.[53] A 2007 study found that the vaccination does not seem to increase the risk of a first episode of MS in childhood.[54] Hepatitis B vaccination has not been linked to onset of autoimmune diseases in adulthood.[55]
The following is a list of countries by the percentage of infants receiving three doses of hepatitis B vaccine as published by theWorld Health Organization (WHO) in 2017 compared to 2022.[57]
| Hepatitis B (HepB3) immunization coverage among one-year-olds worldwide | ||
|---|---|---|
| Country | 2017 Coverage | 2022 Coverage |
| Afghanistan | 66 | 69 |
| Albania | 99 | 97 |
| Algeria | 91 | 77 |
| Andorra | 98 | 96 |
| Angola | 56 | 42 |
| Antigua and Barbuda | 95 | 99 |
| Argentina | 86 | 81 |
| Armenia | 94 | 96 |
| Australia | 95 | 94 |
| Austria | 90 | 84 |
| Azerbaijan | 95 | 83 |
| Bahamas | 94 | 87 |
| Bahrain | 98 | 97 |
| Bangladesh | 98 | 98 |
| Barbados | 90 | 86 |
| Belarus | 98 | 98 |
| Belgium | 97 | 97 |
| Belize | 88 | 84 |
| Benin | 76 | 76 |
| Bhutan | 98 | 98 |
| Bolivia (Plurinational State of) | 84 | 69 |
| Bosnia and Herzegovina | 77 | 78 |
| Botswana | 95 | 86 |
| Brazil | 82 | 77 |
| Brunei Darussalam | 99 | 99 |
| Bulgaria | 92 | 91 |
| Burkina Faso | 91 | 91 |
| Burundi | 91 | 91 |
| Côte d'Ivoire | 83 | 76 |
| Cabo Verde | 97 | 94 |
| Cambodia | 90 | 85 |
| Cameroon | 74 | 68 |
| Canada | 71 | 83 |
| Central African Republic | 42 | 42 |
| Chad | 41 | 60 |
| Chile | 93 | 96 |
| China | 99 | 99 |
| Colombia | 92 | 87 |
| Comoros | 91 | 88 |
| Congo | 69 | 78 |
| Cook Islands | 99 | 72 |
| Costa Rica | 97 | 94 |
| Croatia | 92 | 90 |
| Cuba | 99 | 99 |
| Cyprus | 97 | 94 |
| Czechia | 94 | 94 |
| Democratic People's Republic of Korea | 97 | 0 |
| Democratic Republic of the Congo | 71 | 65 |
| Djibouti | 76 | 59 |
| Dominica | 91 | 92 |
| Dominican Republic | 81 | 87 |
| Ecuador | 85 | 70 |
| Egypt | 94 | 97 |
| El Salvador | 92 | 75 |
| Equatorial Guinea | 53 | 53 |
| Eritrea | 95 | 95 |
| Estonia | 92 | 85 |
| Eswatini | 90 | 97 |
| Ethiopia | 68 | 65 |
| Fiji | 91 | 99 |
| France | 90 | 95 |
| Gabon | 75 | 60 |
| Gambia | 92 | 79 |
| Georgia | 91 | 85 |
| Germany | 88 | 87 |
| Ghana | 99 | 99 |
| Greece | 96 | 96 |
| Grenada | 96 | 77 |
| Guatemala | 91 | 79 |
| Guinea | 47 | 47 |
| Guinea-Bissau | 79 | 74 |
| Guyana | 97 | 98 |
| Haiti | 64 | 51 |
| Honduras | 90 | 78 |
| India | 89 | 93 |
| Indonesia | 85 | 86 |
| Iran (Islamic Republic of) | 99 | 99 |
| Iraq | 81 | 93 |
| Ireland | 95 | 93 |
| Israel | 97 | 96 |
| Italy | 94 | 95 |
| Jamaica | 93 | 98 |
| Japan | no data | 96 |
| Jordan | 99 | 77 |
| Kazakhstan | 99 | 99 |
| Kenya | 82 | 90 |
| Kiribati | 90 | 91 |
| Kuwait | 99 | 96 |
| Kyrgyzstan | 92 | 90 |
| Lao People's Democratic Republic | 84 | 80 |
| Latvia | 98 | 95 |
| Lebanon | 80 | 67 |
| Lesotho | 87 | 87 |
| Liberia | 80 | 78 |
| Libya | 96 | 73 |
| Lithuania | 94 | 90 |
| Luxembourg | 94 | 96 |
| Madagascar | 65 | 57 |
| Malawi | 88 | 86 |
| Malaysia | 98 | 96 |
| Maldives | 99 | 99 |
| Mali | 77 | 77 |
| Malta | 88 | 98 |
| Marshall Islands | 82 | 87 |
| Mauritania | 76 | 76 |
| Mauritius | 96 | 95 |
| Mexico | 58 | 83 |
| Micronesia (Federated States of) | 80 | 75 |
| Monaco | 99 | 99 |
| Mongolia | 99 | 95 |
| Montenegro | 73 | 45 |
| Morocco | 99 | 99 |
| Mozambique | 88 | 61 |
| Myanmar | 89 | 71 |
| Namibia | 88 | 84 |
| Nauru | 87 | 98 |
| Nepal | 90 | 90 |
| Netherlands | 92 | 88 |
| New Zealand | 94 | 89 |
| Nicaragua | 98 | 92 |
| Niger | 85 | 84 |
| Nigeria | 55 | 62 |
| Niue | 99 | 99 |
| North Macedonia | 91 | 84 |
| Norway | no data | 96 |
| Occupied Palestinian Territory, including east Jerusalem | 99 | 99 |
| Oman | 99 | 99 |
| Pakistan | 75 | 85 |
| Palau | 98 | 87 |
| Panama | 81 | 87 |
| Papua New Guinea | 36 | 36 |
| Paraguay | 91 | 69 |
| Peru | 89 | 82 |
| Philippines | 80 | 72 |
| Poland | 93 | 90 |
| Portugal | 98 | 99 |
| Qatar | 97 | 98 |
| Republic of Korea | 98 | 97 |
| Republic of Moldova | 89 | 90 |
| Romania | 92 | 85 |
| Russian Federation | 97 | 97 |
| Rwanda | 98 | 98 |
| Saint Kitts and Nevis | 98 | 96 |
| Saint Lucia | 80 | 81 |
| Saint Vincent and the Grenadines | 99 | 99 |
| Samoa | 67 | 76 |
| San Marino | 82 | 91 |
| São Tomé and Príncipe | 95 | 97 |
| Saudi Arabia | 98 | 98 |
| Senegal | 93 | 88 |
| Serbia | 93 | 92 |
| Seychelles | 97 | 97 |
| Sierra Leone | 90 | 91 |
| Singapore | 96 | 96 |
| Slovakia | 96 | 97 |
| Slovenia | no data | 89 |
| Solomon Islands | 83 | 89 |
| Somalia | 42 | 42 |
| South Africa | 84 | 85 |
| Spain | 94 | 93 |
| Sri Lanka | 99 | 98 |
| Sudan | 95 | 84 |
| Suriname | 67 | 77 |
| Sweden | 76 | 94 |
| Switzerland | 69 | 76 |
| Syrian Arab Republic | 48 | 46 |
| Tajikistan | 96 | 97 |
| Thailand | 99 | 97 |
| Timor-Leste | 83 | 86 |
| Togo | 83 | 82 |
| Tonga | 99 | 99 |
| Trinidad and Tobago | 89 | 93 |
| Tunisia | 98 | 97 |
| Turkiye | 96 | 99 |
| Turkmenistan | 99 | 98 |
| Tuvalu | 96 | 91 |
| Uganda | 94 | 89 |
| Ukraine | 52 | 62 |
| United Arab Emirates | 98 | 95 |
| United Republic of Tanzania | 90 | 88 |
| United Kingdom of Great Britain and Northern Ireland | no data | 92 |
| United States of America | 91 | 93 |
| Uruguay | 93 | 94 |
| Uzbekistan | 99 | 99 |
| Vanuatu | 85 | 68 |
| Venezuela (Bolivarian Republic of) | 66 | 56 |
| Viet Nam | 94 | 91 |
| Yemen | 68 | 74 |
| Zambia | 94 | 82 |
| Zimbabwe | 89 | 90 |
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.[58] 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.[58] 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.[58] The CDC also reports higher HepB vaccine uptake for adults who travel compared to those who do not, 43.1% compared to 28.7%.[58]
In 1963, the American physician/geneticistBaruch Blumberg, working at theFox Chase Cancer Center, discovered what he called the "Australia Antigen" (HBsAg) in the serum of anAustralianAboriginal person.[59] In 1968, this protein was found to be part of the virus that causes "serum hepatitis" (hepatitis B) byvirologistAlfred Prince.[60]
In 1976, Blumberg won theNobel Prize in Physiology or Medicine for his work on hepatitis B (sharing it withDaniel Carleton Gajdusek for his work onkuru).[61] 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.[62] 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 interestMerck, which had considerable experience with vaccines."
During the next few years, a series of human and primate observations by scientists includingMaurice 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 atMerck used three treatments (pepsin,urea andformaldehyde) 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.[63]
Hilleman collected blood from gay men andintravenous drug users—groups known to be at risk forviral 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.[63]
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. (SeeWolf 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.[63] The vaccine was approved in 1981.[17]
The blood-derived hepatitis B vaccine was withdrawn from the marketplace in 1986, replaced byMaurice Hilleman's improved recombinant hepatitis B vaccine which was approved by theFDA on 23 July 1986.[17][19][64] It was the first human vaccine produced by recombinant DNA methods.[64] For this work, scientists atMerck & Co. collaborated withWilliam J. Rutter and colleagues at theUniversity of California at San Francisco, as well as Benjamin Hall and colleagues at theUniversity of Washington.[65] In 1981, William J. Rutter,Pablo DT Valenzuela and Edward Penhoet (UC Berkeley) co-founded theChiron Corporation inEmeryville, California, which collaborated with Merck.[65][66]
The recombinant vaccine is based on a Hepatitis B surface antigen (HBsAg) gene inserted intoyeast (Saccharomyces cerevisiae) cells which are free of any concerns associated with human blood products.[17][67] This allows the yeast to produce only the noninfectious surface protein, without any danger of introducing actual viral DNA into the final product.[63] The vaccine contains theadjuvant amorphous aluminum hydroxyphosphate sulfate.[67]
In 2017, a two-dose HBV vaccine for adults, Heplisav-B gained U.S.Food and Drug Administration (FDA) approval.[4] It uses recombinant HB surface antigen, similar to previous vaccines, but includes a novel CpG 1018 adjuvant, a 22-merphosphorothioate-linked oligodeoxynucleotide. It was non-inferior concerning immunogenicity.[68]
In November 2021, a new hepatitis B recombinant subunit vaccine (Prehevbrio) was approved by the FDA.[7][69][70][71]
The US CDCACIP first recommended the vaccine for all newborns in 1991.[72] 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.[73] 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).[73] 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.[73] For infants born to mothers with positive or unknown Hepatitis B status, a follow up screening is recommended between 9 and 12 months.[73]
The vaccine contains one of the viral envelopeproteins, Hepatitis B surface antigen (HBsAg). It is produced by yeast cells, into which the gene for HBsAg has been inserted.[67] Afterward an immune systemantibody to HBsAg is established in the bloodstream. The antibody is known asanti-HBs. This antibody and immune system memory then provide immunity to hepatitis B virus (HBV) infection.[74]
On 10 December 2020, theCommittee for Medicinal Products for Human Use (CHMP) of theEuropean Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Heplisav B, intended for the active immunization against hepatitis B virus infection (HBV).[75] The applicant for this medicinal product is Dynavax GmbH.[75] It was approved for medical use in the European Union in February 2021.[9]
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).[76] The applicant for this medicinal product is VBI Vaccines B.V.[76] PreHevbri was approved for medical use in the European Union in April 2022.[10][12]
The common brands available are Recombivax HB (Merck),[5] Engerix-B (GSK),[6] Elovac B (Human Biologicals Institute, a division ofIndian Immunologicals Limited), Genevac B (Serum Institute), Shanvac B, Heplisav-B,[4][9] Prehevbrio,[7] and Euvax B (LG Chem).[77]
Twinrix (GSK) is a vaccine againsthepatitis A and hepatitis B.[78][79]
Pediarix is a vaccine againstdiphtheria,tetanus,pertussis, hepatitis B, andpoliomyelitis.[80]
Vaxelis is a vaccine against diphtheria, tetanus, pertussis, poliomyelitis,Haemophilus influenzae type B (Meningococcal Protein Conjugate), and hepatitis B.[81][82]
Fendrix (hepatitis B (rDNA) vaccine (adjuvanted, adsorbed)) was approved for medical use in the European Union in 2005.[83]
