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Hepatitis B vaccine
Hepatitis B vaccine
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Hepatitis B vaccine
Hepatitis B vaccine
Vaccine description
TargetHepatitis B virus
Vaccine typeSubunit
Clinical data
Trade namesRecombivax HB, Engerix-B, Heplisav-B, others
AHFS/Drugs.comMonograph
MedlinePlusa607014
License data
Pregnancy
category
Routes of
administration		Intramuscular (IM)
Drug classAntiviral
ATC code
Legal status
Legal status
Identifiers
PubChem CID
DrugBank
ChemSpider
  • none
UNII
KEGG
 ☒NcheckY (what is this?)  (verify)

Hepatitis B vaccine is a vaccine that prevents hepatitis 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 with poor immune function such as from HIV/AIDS and those born premature.[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 the hepatitis B virus (HBV) but not immunized, hepatitis B immune globulin should be given in addition to the vaccine.[13] The vaccine is given by injection 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 during pregnancy or while breastfeeding.[13] It has not been linked to Guillain–Barré syndrome.[13] Hepatitis B vaccines are produced with recombinant DNA techniques and contain immunologic 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 the World Health Organization's List of Essential Medicines.[16] Both versions were developed by Maurice Hilleman and his team.[17][18][19]

Medical uses

[edit]

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 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.[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, including men 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) and recombinant vaccine (RV), seems to be able to elicit similar protective anti-HBs levels.[14]

The US Centers for Disease Control and Prevention (CDC) issued recommendations for vaccination against hepatitis B among patients with diabetes mellitus.[24] 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] 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, and poliomyelitis is approved in the U.S. and is recommended by the Advisory 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 with hepatitis B virus (HBV).[29] The combination is superior for protecting these infants.[29] The effectiveness of being vaccinated during pregnancy to prevent vertical transmission of hepatitis B to infants has not been studied.[30] Hepatitis B immunoglobulin before birth has not been well studied.[31]

Effectiveness

[edit]

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.[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; 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.[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 to intradermal injection[34] or to a high dose vaccine[35] or to a double dose of a combined hepatitis A and B vaccine.[36] Those who still fail to respond will require hepatitis B immunoglobulin (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, and tobacco smoking,[34][37] and also in alcoholics, especially if with advanced liver disease.[38] People who are immunosuppressed or on dialysis 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 with HIV.[39] The immune response to the hepatitis B vaccine can be impaired by the presence of parasitic infections such as helminthiasis.[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]

Duration of protection

[edit]

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 an anamnestic response, i.e. to rapidly bump up antibody levels when the previously seen antigen is detected.[44][45] 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.[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]

Side effects

[edit]

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, during pregnancy or while breastfeeding.[13][48] It has not been linked to Guillain–Barré syndrome.[13]

Multiple sclerosis

[edit]

Several studies have looked for an association between recombinant hepatitis B vaccine and multiple 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 and sudden 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]

Usage

[edit]
Share of one-year-olds vaccinated against hepatitis B, 2017[56]

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.[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]

History

[edit]

Preliminary work

[edit]

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.[59] In 1968, this protein was found to be part of the virus that causes "serum hepatitis" (hepatitis B) by virologist Alfred Prince.[60]

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).[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 interest Merck, which had considerable experience with vaccines."

Blood-derived vaccine

[edit]

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.[63]

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.[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. (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.[63] The vaccine was approved in 1981.[17]

Recombinant vaccine

[edit]

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.[17][19][64] It was the first human vaccine produced by recombinant DNA methods.[64] 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.[65] 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.[65][66]

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.[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 the adjuvant 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-mer phosphorothioate-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]

Immunization schedule

[edit]

The US CDC ACIP 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]

Manufacture

[edit]

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.[67] 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.[74]

Society and culture

[edit]
[edit]

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 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]

Brand names

[edit]

The common brands available are Recombivax HB (Merck),[5] Engerix-B (GSK),[6] Elovac B (Human Biologicals Institute, a division of Indian 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 against hepatitis A and hepatitis B.[78][79]

Pediarix is a vaccine against diphtheria, tetanus, pertussis, hepatitis B, and poliomyelitis.[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]

References

[edit]

Further reading

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Hepatitis B vaccine

View on Grokipedia
from Grokipedia
The Hepatitis B vaccine is a preventive immunization against hepatitis B, a viral infection caused by the hepatitis B virus (HBV) that targets the liver and can lead to acute illness, chronic liver disease, cirrhosis, or hepatocellular carcinoma. It consists of highly purified recombinant hepatitis B surface antigen (HBsAg), produced using yeast cells via DNA recombinant technology, and is typically administered as a series of two or three intramuscular injections. The vaccine induces the production of protective antibodies against HBsAg, providing immunity without causing the disease itself. Development of the Hepatitis B vaccine began following the discovery of HBV by Baruch Blumberg in 1965, with the first plasma-derived vaccine, Heptavax-B, receiving U.S. (FDA) approval in 1981 for high-risk groups. Concerns over potential blood-borne contaminants led to the creation of safer recombinant versions; Recombivax HB was the first such vaccine approved by the FDA in 1986, followed by Engerix-B in 1989. These recombinant vaccines, which insert the gene into yeast (), became the standard worldwide by the early 1990s, eliminating reliance on human plasma. Today, multiple formulations exist, including monovalent vaccines and combinations like Twinrix (with ) or Pediarix (with , , pertussis, and components). The vaccine is highly effective, conferring protective antibody levels in over 95% of healthy infants, children, and adults after completing the primary series, with immunity lasting at least 20 years and likely lifelong in most recipients. Studies show it prevents chronic HBV infection, which affects an estimated 254 million people globally as of 2022 and causes about 1.1 million deaths annually from liver complications. Safety profiles are excellent, with the most common side effect being mild soreness at the injection site; serious adverse events are rare, occurring at rates no higher than background levels in unvaccinated populations. No evidence links the vaccine to conditions like or . Universal vaccination recommendations were established by the (WHO) in 1992 and the U.S. Centers for Disease Control and Prevention (CDC) in 1991, prioritizing a birth dose within 24 hours to prevent perinatal transmission, followed by additional doses at 1–2 and 6 months of age. The CDC advises routine immunization for all infants, unvaccinated children and adolescents under 19, adults aged 19–59, and adults 60 and older with risk factors such as occupational exposure, travel to endemic areas, or multiple sexual partners. Globally, vaccination has reduced chronic HBV prevalence in children under five from about 5% before widespread use to under 1% by 2019, averting millions of infections and demonstrating one of the most successful interventions in modern history.

Medical uses

Prevention of infection

The (HBV) is a partially double-stranded belonging to the family that primarily infects hepatocytes, leading to acute or ranging from asymptomatic infection to and . The HBV vaccine, composed of recombinant hepatitis B surface (HBsAg) particles, stimulates the production of protective antibodies (anti-HBs) that neutralize the virus by binding to HBsAg on the viral surface, thereby preventing viral attachment and entry into liver cells. This immune response effectively blocks HBV transmission through exposure to infected blood or bodily fluids, reducing the risk of both acute infection and progression to chronic carriage. The vaccine plays a critical role in interrupting mother-to-child (vertical) transmission, which accounts for the majority of chronic infections in high-endemicity regions, where perinatal exposure during birth can lead to chronicity in 90% of cases without intervention, compared to approximately 5% in adults. Prior to universal infant vaccination, an estimated 18,000 to 20,000 children younger than 10 years became infected annually in the United States, with roughly half via perinatal transmission despite maternal screening (due to false negatives or late maternal acquisition) and half via horizontal transmission through close household contact with undiagnosed carriers. HBV is highly contagious and remains infectious on environmental surfaces for at least 7 days, heightening risks in early infancy even absent identified high-risk factors; targeted vaccination strategies failed to substantially reduce overall pediatric incidence, underscoring the need for universal birth dosing as a safety net, with the vaccine's safety profile comparable at birth to later administration. Administering the first vaccine dose within 24 hours of birth, combined with hepatitis B immune globulin (HBIG) for infants born to HBsAg-positive mothers, provides 85-95% protection against perinatal infection and reduces chronic infection rates to less than 5%. For horizontal transmission—spread through close household contact, unsafe injections, or sexual exposure—the vaccine prevents infection in high-risk groups such as healthcare workers exposed to needlestick injuries and individuals with multiple sexual partners, significantly lowering community-level incidence. In healthy adults and children, completion of the three-dose vaccine series confers approximately 95% against HBV , with seroprotection defined as anti-HBs levels of at least 10 mIU/mL. This prophylactic approach is recommended universally for infants and routinely for at-risk adults to establish long-term immunity prior to potential exposure. In contrast, is indicated for unvaccinated or incompletely vaccinated individuals following high-risk exposures, such as perinatal contact or injuries, involving immediate administration of HBIG alongside the vaccine series to provide passive and active immunity, ideally within 24 hours.

Effectiveness in populations

The hepatitis B vaccine demonstrates high efficacy in preventing infection across most populations, with seroprotection rates of 90-95% achieved after a complete three-dose series in healthy infants and immunocompetent adults. In infants, particularly those receiving the birth dose followed by additional doses, the vaccine provides 85-95% protection against perinatal transmission when combined with hepatitis B immune globulin (HBIG) in cases of maternal infection. However, efficacy is notably reduced in certain high-risk groups, such as dialysis patients and immunocompromised individuals, where response rates range from 50-70%, often necessitating higher doses, intradermal administration, or revaccination to improve outcomes. In newborns of hepatitis B surface antigen (HBsAg)-positive mothers, the vaccine significantly reduces the risk of developing chronic HBV infection, with studies showing a 70-90% decrease in chronic carrier rates when vaccination is initiated at birth alongside HBIG. This intervention is particularly impactful in high-endemicity settings, where perinatal transmission accounts for up to 90% of chronic infections in infancy, preventing long-term complications like and . Breakthrough infections remain rare, occurring primarily in non-responders who constitute 5-10% of vaccinees and fail to develop protective anti-HBs levels. Factors influencing non-response include , , older age at vaccination, and genetic variations such as specific (HLA) types, which impair immune recognition and antibody production. These infections are typically mild and do not lead to chronicity in immunocompetent individuals, underscoring the vaccine's role in conferring partial cellular immunity even in humoral non-responders. Long-term population-level studies highlight the vaccine's profound impact on HBV . In , the nationwide universal program launched in resulted in an approximately 90% reduction in chronic carrier rates from about 10% to less than 1% over three decades. Similarly, in , where HBV was hyperendemic among , implementation of targeted and screening programs from the early 1980s led to a greater than 90% drop in acute HBV incidence and near-elimination of perinatal transmission by the 1990s. These programs demonstrate how sustained high coverage (>90% in infants) can interrupt transmission chains and reduce at a community scale.

Duration of protection

The hepatitis B vaccine induces long-term immunity, with anti-HBs antibodies remaining detectable in 80-100% of vaccinated individuals for 20-30 years or more, and protection against chronic disease persisting lifelong in the majority of healthy recipients. Studies following vaccinated cohorts have demonstrated sustained protection for at least 30 years in those immunized as infants, with no evidence of chronic infection despite occasional loss of detectable antibodies. A 35-year follow-up of vaccine recipients showed that 86% maintained protective immunity, either through persistent anti-HBs levels ≥10 mIU/mL or a robust anamnestic response to a . Antibody levels typically decline after 10-15 years post-vaccination, often falling below the protective threshold of 10 mIU/mL in some individuals, yet cellular immune continues to confer protection against clinically significant infection. This waning of does not equate to loss of overall protection, as vaccinated persons rarely develop chronic even when antibody titers become undetectable. Consequently, routine booster doses are not recommended for healthy, immunocompetent individuals regardless of age or time since primary vaccination. Booster vaccination is indicated for high-risk groups, such as healthcare workers exposed to or bodily fluids and patients on dialysis, if serological testing reveals anti-HBs levels below 10 mIU/mL. In these populations, revaccination with a complete series or additional doses may be necessary to restore protective antibody levels, particularly if initial response to the primary series was suboptimal. Guidelines from health authorities recommend serological monitoring of titers in select at-risk populations to evaluate the need for revaccination, typically 1-2 months after completing the primary series or prior to ongoing exposure scenarios. For example, healthcare personnel and patients should undergo periodic anti-HBs testing to ensure ongoing immunity, with revaccination advised only if levels are inadequate. Such targeted surveillance helps maintain protection without widespread booster use. In high-risk perinatal cases, maternal antiviral therapy (e.g., tenofovir) combined with and HBIG can further enhance prevention to over 95% as of guidelines.

Safety profile

Common adverse reactions

The most common adverse reactions following administration of the hepatitis B are mild and transient, typically resolving without intervention within 1 to 2 days. Local reactions at the injection site, including pain, soreness, redness (), or swelling, are reported in 3% to 29% of recipients based on data. These effects are attributed to the physical trauma of injection and the to the , and they occur similarly across age groups, though injection site pain may be more noticeable in adults due to larger muscle mass. Systemic reactions are less frequent but include mild fever (temperature greater than 37.7°C) in 1% to 6% of cases, along with , , or in 1% to 10%. Such effects tend to be more common in infants and young children than in adults, possibly due to differences in immune maturation and reporting practices in pediatric populations. Mild allergic responses, such as urticaria or , occur in fewer than 1% of recipients and are generally self-limited, distinct from severe . Data from postmarketing surveillance systems, including the U.S. (VAERS), show overall reporting rates of approximately 11.8 adverse events per 100,000 doses administered, with the vast majority classified as mild and non-serious. These systems underreport mild events due to their expected nature, but they confirm the vaccine's favorable safety profile for routine use.

Rare serious effects

Anaphylaxis is a rare but potentially life-threatening allergic reaction following vaccination, with an estimated incidence of 1.1 cases per million doses administered. This hypersensitivity response typically occurs within minutes to hours after vaccination and is managed effectively with immediate administration of epinephrine, along with supportive care such as and monitoring for biphasic reactions. Neurological events, including Guillain-Barré syndrome (GBS), have been reported after vaccination at rates not exceeding background population incidence, with surveillance data indicating fewer than 1 case per million doses and no established causal link beyond expected rates. GBS, characterized by acute and potential , usually resolves with supportive treatment, but post-vaccination cases align with the general annual incidence of 1-2 per 100,000 individuals unrelated to . Concerns about an association between vaccination and (MS) emerged in the early 1990s from French studies reporting elevated notification rates of 0.6 per 100,000 doses during a mass immunization campaign, prompting temporary suspension of school-based programs. However, subsequent large-scale epidemiological analyses, including the 2002 Institute of Medicine (IOM) report, found no evidence of a causal relationship, rejecting the hypothesis based on meta-analyses of cohort and case-control studies showing relative risks near 1.0. Current guidelines affirm that vaccination is safe for individuals with MS or at risk for it, with no increased incidence of onset or exacerbation observed in vaccinated populations. Isolated cases of and have been documented post-vaccination, occurring in fewer than 0.01% of recipients, though causality remains unproven and rates do not exceed background levels in databases. , involving low platelet counts potentially leading to bleeding, and reactive , with joint inflammation, typically resolve spontaneously or with standard therapies, but require monitoring in affected individuals. For newborns receiving the hepatitis B vaccine, immediate medical attention should be sought if the following signs of potential serious reaction occur: persistent high fever over 38.5°C; severe vomiting or diarrhea; unusual drowsiness or extreme irritability with abnormal crying; rapid breathing, purple lips, or large areas of rash or swelling; convulsions or other unusual behaviors. Ongoing global surveillance through systems like the (VAERS) and WHO's Global Vaccine Safety Initiative continues to track these events, confirming their rarity and supporting the vaccine's overall safety profile.

Contraindications and precautions

The primary absolute to administration of the recombinant hepatitis B is a history of severe allergic reaction, such as , to a previous dose or to any component of the , including . This is rare, with occurring at an estimated rate of approximately 1 per million doses. Vaccination should generally be postponed in individuals experiencing moderate or severe acute illness, with or without fever, to avoid confounding symptoms or complicating the assessment of potential adverse events; however, minor illnesses like a do not require deferral. is not a , as available data indicate no increased risk of adverse outcomes for the or mother, though the adjuvant-containing Heplisav-B formulation is not routinely recommended due to limited safety information. also poses no barrier to vaccination, with no of harm to the via transmission. In special populations, individuals who are immunocompromised, including those on immunosuppressive therapy such as corticosteroids, may exhibit a reduced and thus require higher doses, additional doses, or post-vaccination serologic monitoring to confirm immunity. For neonates born to surface antigen (HBsAg)-positive mothers, vaccination should commence within 12 hours of birth, administered concurrently with hepatitis B immune globulin (HBIG) at separate anatomic sites to provide immediate prophylaxis against perinatal transmission. These infants typically follow an adjusted dosing schedule based on birth weight, with post-vaccination testing to verify protection. No significant drug interactions preclude hepatitis B vaccination, though immunosuppressive agents like corticosteroids can blunt the response without constituting a ; vaccination remains recommended with appropriate follow-up testing in such cases.

Administration

Vaccination schedules

The standard vaccination schedule for the (HepB) vaccine in infants involves a three-dose series administered universally in many countries to prevent perinatal and early childhood transmission. This approach, including the birth dose, provides practical benefits: infants infected with hepatitis B virus (HBV) have approximately a 90% chance of developing chronic infection—leading to cirrhosis or liver cancer later in life—compared to about 5% in adults. Prior to universal vaccination, around 20,000 children under age 10 acquired HBV annually in the United States, roughly half via mother-to-child transmission despite screening (due to false negatives, misses, or late maternal acquisition) and half through household or casual contact with undiagnosed carriers, as HBV is highly contagious and survives on surfaces for at least 7 days. Targeted vaccination of identifiable high-risk groups failed to significantly reduce pediatric infections, whereas universal strategies have virtually eliminated acute HBV in children. The birth dose serves as a safety net against early exposures, with a safety profile equivalent to later dosing and no additional risks from administration at birth. The first dose is given within 24 hours of birth (or as soon as possible thereafter), the second dose at 1–2 months of age, and the third dose between 6 and 18 months of age, with the minimum interval between the first and third doses being 16 weeks. This birth dose is particularly critical for infants born to mothers with unknown or positive surface antigen () status, where immune (HBIG) is also administered concurrently with the first vaccine dose within 12 hours of birth. The (WHO) endorses this approach globally, recommending the birth dose within 24 hours followed by 2–3 additional doses integrated into the routine infant schedule to achieve at least three doses by 6 months of age. For unvaccinated adults and older adolescents, the recommended schedule is a three-dose series of monovalent HepB vaccine (such as Engerix-B or Recombivax HB) given at 0, 1, and 6 months, providing protective levels in over 90% of healthy recipients. High-risk adults, including healthcare workers or those anticipating imminent exposure (e.g., travelers to endemic areas), may receive an accelerated schedule using the combination (Twinrix): three doses at 0, 7, and 21–30 days, followed by a booster at 12 months. Alternative two-dose options are available for adults aged 18 years and older using Heplisav-B (at 0 and 1 month) or for adolescents aged 11–15 years using the adult formulation of Recombivax HB (at 0 and 4–6 months). WHO guidelines align with the three-dose adult series for at-risk populations, emphasizing completion within 6–12 months. Catch-up vaccination targets unvaccinated children and adolescents up to 19 years of age, following the standard three-dose at 0, 1–2, and 6 months to ensure immunity before potential risk exposures. Minimum intervals must be observed (4 weeks between doses 1 and 2, 8 weeks between doses 2 and 3), but the series does not need restarting if delays occur. In cases of known or suspected post-exposure to (e.g., or ), unvaccinated or incompletely vaccinated individuals receive a single dose of HepB vaccine immediately (preferably within 24 hours), along with HBIG for those at highest risk (e.g., source HBsAg-positive), followed by completion of the full three-dose series at 1 and 6 months post-initial dose. Post-vaccination serologic testing is recommended 1–2 months after the final dose to confirm immunity (anti-HBs ≥10 mIU/mL).

Dosing and routes

The Hepatitis B vaccine formulations vary by manufacturer, but standard single-antigen vaccines contain recombinant hepatitis B surface antigen () as the active component. For pediatric patients from birth through 19 years, the recommended dose is typically 5–10 mcg of in a 0.5 mL volume. For adults aged 20 years and older, the dose is 10–20 mcg of in 0.5–1 mL, with higher amounts (e.g., 40 mcg in 1 mL) for those on to account for potential immune compromise. Administration occurs via , with the preferred for adults and children aged 1 year and older, and the anterolateral for infants younger than 1 year to ensure optimal absorption and minimize complications. Intravenous or subcutaneous routes must be avoided, as they can lead to suboptimal or increased risk of adverse reactions. may be considered only in patients at high risk of hemorrhage, such as those with hemophilia, though it yields lower responses. Most formulations incorporate aluminum-based adjuvants, such as aluminum hydroxide (0.25–0.5 mg per dose) or amorphous aluminum hydroxyphosphate sulfate, to boost the by promoting and prolonging exposure. The vaccine must be stored refrigerated at 2–8°C (36–46°F) and protected from light; freezing is contraindicated, as it irreversibly damages the and renders the vaccine ineffective. Under proper conditions, the extends 2–3 years from the date of manufacture, after which it should be discarded.

Combination vaccines

Combination vaccines incorporate the (HBV) surface with other vaccine antigens to provide protection against multiple diseases in a single formulation, facilitating more efficient programs. These products are designed to maintain the of individual components while simplifying administration. Common combination vaccines include those pairing HBV with hepatitis A virus (HAV), such as Twinrix, approved for adults aged 18 years and older. For pediatric use, examples are Pediarix, which combines HBV with diphtheria, tetanus, acellular pertussis (DTaP), and inactivated poliovirus (IPV), and Vaxelis, which adds Haemophilus influenzae type b (Hib) conjugate to DTaP, IPV, and HBV. In global settings, pentavalent vaccines combining HBV with diphtheria, tetanus, pertussis, and Hib are widely used for infant immunization. The primary advantages of these vaccines are a reduction in the number of injections, which decreases pain and anxiety for recipients, particularly children, and improves vaccination compliance by minimizing clinic visits. Studies show that HBV in combination formulations is equivalent to that of monovalent vaccines, ensuring comparable protection against HBV infection. Vaccination schedules for combination products are adjusted to align with routine immunization timelines for the included antigens; for instance, pediatric combinations like Pediarix or Vaxelis are typically administered as three doses at 2, 4, and 6 months of age. For adult-targeted Twinrix, the schedule consists of three doses at 0, 1, and 6 months. Limitations include age restrictions, as many pediatric combinations are approved only for infants and young children, while adult formulations like Twinrix are not suitable for those under 18 years. Additionally, combination vaccines can have higher per-dose costs compared to separate monovalent vaccines in certain healthcare settings, potentially affecting accessibility in resource-limited areas.

Development and history

Early research

The discovery of the Australia antigen, now known as the hepatitis B surface antigen (HBsAg), marked a pivotal advancement in understanding (HBV) in the 1960s. Baruch S. Blumberg and colleagues first identified this antigen in 1965 while studying serum proteins in patients with and Down's syndrome, using serum from an Australian Aboriginal donor that reacted with multiple samples. Subsequent work by Blumberg's team in 1967 linked the antigen to cases of serum (type B), demonstrating its presence in patients with acute and establishing it as a marker for HBV infection. This breakthrough, for which Blumberg received the in Physiology or Medicine in 1976, shifted research toward the viral etiology of what was previously termed "serum hepatitis." In the early 1970s, further virological insights emerged through electron microscopy and serological advancements. David S. Dane and colleagues identified 42-nm virus-like particles, termed Dane particles, in sera positive for Australia antigen, confirming these as the complete HBV virions with an outer envelope containing and an inner core. Concurrently, sensitive serological tests, including radioimmunoassays (RIA), were developed to detect and anti-HBs antibodies, enabling more precise diagnosis and epidemiological tracking of HBV. These tools revealed the antigen's , as it elicited protective antibodies in infected individuals, laying the conceptual groundwork for strategies targeting . Animal model studies in the 1970s provided critical confirmation of HBV's infectivity and pathogenesis. Chimpanzees, the only nonhuman susceptible to human HBV, were experimentally infected with HBsAg-positive human serum, replicating acute with , liver elevations, and histological changes mirroring human . These experiments, first reported by Alfred M. Prince in 1972, validated the Dane particle as the infectious agent and demonstrated chronic carrier states in some animals, informing development by highlighting the need for immunity against HBsAg. Epidemiological investigations during this period clarified HBV transmission risks. Studies established as the primary route, with parenteral exposure via contaminated needles or transfusions leading to infection, while sexual transmission through and perinatal exposure from infected mothers to infants were identified as key non-parenteral pathways. These findings underscored the virus's global burden and the urgency for preventive measures.

Plasma-derived vaccines

The first plasma-derived hepatitis B vaccines were developed in the mid-1970s through the purification of hepatitis B surface antigen () from the plasma of asymptomatic chronic carriers. Merck Sharp & Dohme initiated this process in 1975, employing techniques such as ultracentrifugation to isolate and concentrate the antigen, followed by inactivation steps including digestion at low , treatment with 8M to disrupt viral structure, and inactivation to eliminate any residual infectivity. These methods ensured the vaccine, marketed as Heptavax-B, contained only the noninfectious HBsAg particles necessary to stimulate an without viable virus. Clinical trials in the late and early confirmed the vaccine's , particularly among high-risk adults. A landmark double-blind, placebo-controlled study involving 1,083 homosexual men—a group with high incidence—demonstrated a protective of 92% after three doses, with no cases of clinical or chronic antigenemia among responders. Similar results were observed in healthcare workers, where rates reached 80-95%, significantly reducing infection rates compared to unvaccinated controls. Based on these data, the U.S. approved Heptavax-B in November 1981 for use in adults at elevated risk, marking the first licensed vaccine against . Despite its effectiveness, plasma-derived vaccines faced significant limitations that restricted widespread adoption. The reliance on human plasma created supply constraints, as sourcing sufficient quantities from screened carriers was logistically challenging and dependent on donor availability. Although multi-step purification and inactivation minimized risks, theoretical concerns persisted regarding potential transmission of blood-borne pathogens like , which was not fully understood until the mid-1980s; no such transmissions were documented, but the plasma origin heightened public apprehension. Additionally, production costs were high—estimated at around $50 per dose initially—limiting accessibility in low-resource settings. By the late , plasma-derived vaccines were phased out in favor of recombinant alternatives, which eliminated plasma sourcing issues and offered greater scalability and perceived safety. The introduction of yeast-derived recombinant vaccines in 1986 accelerated this transition, rendering plasma-based products obsolete in most markets by the early .

Recombinant vaccine era

The recombinant vaccine era for hepatitis B began in 1986 with the U.S. Food and Drug Administration's approval of Recombivax HB, the first genetically engineered vaccine against the virus, developed by Merck Sharp & Dohme. This vaccine utilized recombinant DNA technology to express the hepatitis B surface antigen (HBsAg) in the yeast Saccharomyces cerevisiae, marking a pivotal shift from plasma-derived methods by enabling large-scale production without reliance on human blood donors. Key advantages of recombinant vaccines included the elimination of risks associated with human blood products, such as transmission of or other pathogens, while providing an unlimited and scalable supply that significantly reduced production costs over time. Clinical studies demonstrated that these vaccines achieved rates equivalent to or exceeding those of plasma-derived versions, with antibody concentrations often higher in recipients of the recombinant formulation, confirming their superior in healthy adults. In the , enhancements focused on optimizing formulations for broader populations, including the introduction of higher doses—such as the 20 μg formulation in Engerix-B, approved by the FDA in 1989—for adults to improve response rates in older individuals and those with potential immune challenges. By the 2000s, pediatric-specific formulations with lower doses (e.g., 5–10 μg ) became standard, facilitating safer and more effective infant programs. These innovations built on the foundational recombinant platform to enhance and . The global dissemination of recombinant hepatitis B vaccines was accelerated through patent licensing and (WHO) prequalification processes, which began establishing standards for recombinant production in 1988 and were amended in 1997 to support widespread manufacturing and distribution in developing countries. This framework enabled the vaccine's integration into national immunization schedules worldwide, transitioning from limited plasma-derived supplies to recombinant dominance by the early .

Global implementation

In 1992, the (WHO) issued a pivotal recommendation for universal infant vaccination against hepatitis B, advocating for the inclusion of the vaccine in national immunization programs worldwide to curb the global burden of the disease. This policy shift marked a turning point, emphasizing prevention at birth to interrupt perinatal transmission, particularly in high-endemicity regions. By 2020, the hepatitis B vaccine had been integrated into the Expanded Programme on Immunization (EPI) in over 190 countries, reflecting widespread adoption driven by WHO's technical support and global health partnerships. In the United States, key milestones accelerated domestic implementation. In 1991, the Advisory Committee on Immunization Practices (ACIP) recommended universal infant vaccination, prioritizing newborns regardless of maternal status to achieve long-term population immunity. By the mid-1990s, numerous states enacted school-entry mandates requiring proof of vaccination for children entering middle or high school, with 35 states implementing such requirements by 1997; these policies significantly boosted adolescent coverage and contributed to a decline in acute infections. In 2022, the CDC expanded recommendations to include routine vaccination for all adults aged 19–59 years, regardless of risk factors. Global rollout faced logistical hurdles, particularly in low-income settings where maintaining vaccine potency through infrastructure proved challenging due to unreliable electricity, remote terrains, and limited storage facilities. Overcoming these involved innovations like solar-powered refrigerators and simplified , alongside strategic integration of the hepatitis B vaccine into multi-antigen schedules—such as pentavalent combinations—to streamline delivery without overburdening systems. Post-2020, amid efforts to meet WHO's 2030 elimination targets, there has been increased emphasis on catch-up campaigns in high-prevalence areas like , where chronic infection rates remain elevated despite infant programs; initiatives target high-risk adults, including healthcare workers, to close immunity gaps and accelerate progress toward regional control.

Production

Manufacturing methods

The manufacturing of recombinant hepatitis B vaccines primarily involves the production of hepatitis B surface (HBsAg) using yeast expression systems, followed by purification and formulation steps to yield immunogenic 22-nm virus-like particles. The HBsAg gene is cloned into vectors and expressed in species such as or Hansenula polymorpha, where it self-assembles into non-infectious particles mimicking the . These recombinant cells are cultured in large-scale bioreactors under controlled conditions, typically using complex media to support high-density growth and antigen expression. Purification begins with cell lysis to release intracellular HBsAg particles, followed by a series of chromatographic techniques, including ion-exchange, affinity, and , to remove host cell proteins and impurities. and are employed to concentrate the and further isolate the 22-nm particles, achieving high purity levels often exceeding 95%. For most recombinant hepatitis B vaccines, the purified HBsAg is then adsorbed onto aluminum-based adjuvants, such as aluminum or aluminum hydroxyphosphate , to enhance by facilitating uptake and prolonging immune stimulation. Some formulations, such as Heplisav-B, use alternative adjuvants like the synthetic agonist CpG 1018 instead of aluminum. Formulation of the final vaccine involves suspending the adjuvanted HBsAg in a buffered solution, with pH typically adjusted to 6.2–7.0 for stability and injectability. Some multi-dose presentations, primarily for use in developing countries, include thimerosal as a at concentrations around 1:20,000 (0.005%) to prevent microbial contamination, while single-dose or preservative-free formulations—standard in the U.S. and many high-income settings—omit it to minimize potential sensitivities. Yield improvements in recombinant HBsAg production have been achieved through , such as optimizing promoter sequences and codon usage in vectors, resulting in expression levels up to 300–400 mg/L in H. polymorpha cultures. These advancements, including the use of methylotrophic s like H. polymorpha for efficient methanol-inducible expression, have significantly scaled up efficiency compared to early recombinant processes.

Quality assurance

The production of recombinant hepatitis B vaccines adheres to Good Manufacturing Practice (GMP) standards established by the (WHO) and the U.S. (FDA), ensuring consistent quality through oversight of manufacturing facilities, , and quality systems. WHO guidelines require of production areas, monitoring of staff health, and separation from unauthorized microorganisms, while FDA inspections focus on risk-based for biological products. Batch release testing, conducted by manufacturers and verified by national regulatory authorities (NRAs), includes assessments for sterility, purity, potency, pyrogens/endotoxins, adjuvant content, and appearance to confirm compliance before distribution. Sterility testing follows WHO requirements, inoculating samples into specified media and incubating to detect bacteria or fungi, with results required to be negative for release. Purity is evaluated through methods such as polyacrylamide gel electrophoresis (PAGE) or high-performance liquid chromatography (HPLC), targeting at least 95% purity in the aqueous bulk and over 99% in the final product, with minimal non-HBsAg proteins. Potency assays verify the vaccine's and content, typically exceeding 10 mcg per dose for standard formulations. methods use mouse models to determine the ED50 (effective dose for 50% ) against a reference preparation, with confidence limits of 33-300% accepted by NRAs. immunoassays, such as enzyme-linked immunosorbent assay (), quantify levels and are increasingly used for routine batch testing due to their precision and correlation with results. Contaminant controls limit residual host cell proteins to less than 1-5% of total protein, residual host cell DNA to under 10 ng per dose (with fragments preferably below 200 base pairs to reduce oncogenic risk), and endotoxins to NRA-approved thresholds consistent with clinical safety, often below 5 EU per dose. These limits are enforced through sensitive detection methods like quantitative PCR for DNA and limulus amebocyte lysate assays for endotoxins during purification and final testing. Stability testing involves real-time storage at 2-8°C and accelerated conditions (e.g., 37°C) to monitor potency, , and appearance over time, supporting a typical of 36 months from the date of manufacture or last potency test. NRAs validate expiry dates based on these data, ensuring no significant loss of during the labeled period.

Supply and distribution

The Hepatitis B vaccine is primarily produced by a handful of major manufacturers, with key players in the United States and Europe including GlaxoSmithKline (GSK), Sanofi, Dynavax Technologies, and Merck & Co., which supply vaccines such as Engerix-B, Recombivax HB, and Heplisav-B. In developing countries, production is led by institutions like the Serum Institute of India and Bio-Manguinhos (part of Fiocruz in Brazil), which focus on affordable, recombinant vaccines for regional and global markets. Global production capacity for the Hepatitis B vaccine supports widespread , with estimates indicating hundreds of millions of doses manufactured annually to meet demand from routine childhood programs and adult catch-up campaigns. The Alliance plays a crucial role in procurement for low-income countries, facilitating access to multi-dose vials from suppliers like the and at costs below US$0.30 per dose, while providing grants for introduction and technical support in over 30 eligible nations. Distribution relies on a robust to maintain , requiring storage and at 2–8°C to prevent degradation, though this poses logistical challenges in remote or resource-limited areas where power outages and high temperatures are common. Efforts to address these include the development of stabilizers and controlled temperature chain strategies, allowing limited periods outside standard under monitored conditions. Occasional supply disruptions have occurred, such as the 2017–2018 of Merck's pediatric Recombivax HB , which limited availability until early 2018 due to constraints. These issues were mitigated through diversification, with GSK increasing production of Engerix-B to cover U.S. demand and CDC guidance prioritizing high-risk groups.

Recommendations and impact

Public health guidelines

The (WHO) recommends universal hepatitis B vaccination for all , with the first dose administered as a birth dose within 24 hours of delivery to prevent perinatal transmission, followed by a 3-dose series integrated into routine schedules (e.g., at 6, 10, and 14 weeks or 2, 4, and 6 months). For unvaccinated children and adolescents up to age 18, catch-up vaccination is advised, while adults in high-risk groups—such as healthcare workers, people who inject drugs, and those with multiple sexual partners—should receive the 3-dose series (0, 1, and 6 months). In the United States, following a December 5, 2025, vote, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) recommends a birth dose of hepatitis B vaccine within 24 hours for infants born to hepatitis B surface antigen (HBsAg)-positive mothers or those with unknown maternal status, while for infants of HBsAg-negative mothers, individual-based clinical decision-making is advised, potentially deferring the initial dose to no earlier than 2 months of age, with the 3-dose series completed by 6–18 months. Catch-up is recommended for all unvaccinated children and adolescents younger than 19 years, and routine is advised for all adults aged 19–59 years to address ongoing transmission risks. For adults aged 60 years and older, is recommended for those with risk factors (e.g., , occupational exposure) and may be considered for others on a shared clinical basis. European Union and European Economic Area (EU/EEA) guidelines, coordinated through the European Centre for Disease Prevention and Control (ECDC), align closely with WHO recommendations, with 27 countries implementing universal infant vaccination as part of routine childhood immunization, typically involving a standard 3-dose schedule starting at birth or 2 months. In high-endemic areas, such as parts of and where hepatitis B prevalence exceeds 8%, WHO prioritizes perinatal screening of pregnant women alongside the birth dose to identify and manage infants at highest risk of chronic infection. As of 2025, major guidelines emphasize improving equity in adult coverage to counter rising acute cases in certain regions, including among unvaccinated adults in low- and middle-income countries and underserved populations in high-income settings, through targeted outreach and simplified access to the series.

Vaccination programs

The Vaccines for Children (VFC) program, launched in 1994 by the U.S. Centers for Disease Control and Prevention (CDC), provides no-cost vaccines, including the , to eligible children aged 0–18 years who are uninsured, Medicaid-eligible, or American Indian/Alaska Native, ensuring broad access to routine . This initiative has significantly boosted infant vaccination rates, achieving over 90% coverage for the birth dose and exceeding 94% for the full series among kindergarteners by the 2024–2025 school year. Taiwan's universal hepatitis B vaccination program, initiated on July 1, 1984, targeted newborns of carrier mothers initially and expanded to all infants by 1986, marking one of the earliest large-scale national efforts to combat (HBV) transmission. The program has demonstrated profound long-term efficacy, with vaccinated cohorts born after 1984 experiencing an 80% reduction in (HCC) incidence compared to pre-vaccination birth cohorts, alongside sharp declines in mortality. This success is attributed to high compliance rates exceeding 90% for the initial vaccination series, serving as a model for integrating screening and in high-prevalence settings. Through , the Vaccine Alliance, numerous low- and middle-income countries in and have introduced the birth dose in the , often as part of schedules to enhance perinatal protection against HBV. In GAVI-supported countries, coverage for the three-dose series has reached approximately 81% as of 2019, reflecting substantial progress in scaling up supply, cold-chain infrastructure, and community outreach to achieve equitable delivery. These efforts prioritize timely birth dosing within 24 hours to prevent mother-to-child transmission, with ongoing support facilitating integration into routine platforms across endemic regions. In 2023–2024, Gavi resumed funding for birth dose vaccination in several African countries, aiming to boost coverage from around 18% in the region. In , recent vaccination initiatives have increasingly targeted adults, particularly migrants from HBV-endemic areas, through targeted screening and immunization campaigns recommended by the European Centre for Disease Prevention and Control (ECDC). Programs in countries like and the emphasize catch-up vaccination for unvaccinated adults from high-prevalence regions in and , integrating HBV testing with free vaccine access via public health services to address gaps in prior exposure. These campaigns, bolstered by EU-wide guidance since 2023, aim to reduce imported cases and community transmission by prioritizing at-risk groups outside routine childhood schedules.

Global coverage and outcomes

As of 2024, global coverage with the third dose of the among infants reached 84%, reflecting widespread adoption in national immunization programs since the World Health Organization's (WHO) recommendation in 1992. However, timely birth dose administration, critical for preventing mother-to-child transmission, lagged at 45% worldwide, with coverage in low- and middle-income countries estimated around 50% due to challenges in healthcare access and supply chains. These figures represent progress from earlier decades but highlight the need for accelerated efforts to meet WHO's 90% coverage targets by 2030. The vaccine's implementation has led to substantial reductions in (HBV) burden, with global of chronic HBV infection among children under five dropping to under 1% by 2019, a marked decline from over 5% in the pre-vaccine era. Since 1990, incident cases of HBV in children and adolescents have decreased by more than 50%, from 31.4 million to about 14.6 million by 2015, driven primarily by vaccination programs that have averted an estimated tens of millions of infections. Overall, all-age chronic HBV fell by 31.3% between 1990 and 2019, underscoring the vaccine's role in curbing acute and chronic disease transmission. Regional disparities persist, with third-dose coverage exceeding 95% in the and Western Pacific regions, where robust infrastructure supports high immunization rates. In contrast, coverage in the African region remains lower, at 40-60% for the third dose and only 18% for the birth dose, contributing to ongoing transmission hotspots. These gaps exacerbate global inequities, as bears a disproportionate share of new infections despite comprising a smaller population fraction. Mathematical modeling studies project that achieving WHO's 2030 elimination —90% coverage and 80% treatment access for chronic cases—could prevent approximately 26 million (95% CrI 17–35 million) new chronic HBV infections worldwide by scaling up birth dose and full-series . Recent assessments indicate that few countries are on track to meet full HBV elimination by 2030, with most requiring intensified interventions, particularly in low-income regions.

Society and culture

Availability and access

The cost of the hepatitis B vaccine varies widely based on procurement channels and market type, influencing its accessibility in different economic contexts. Through bulk purchasing agreements facilitated by , the Vaccine Alliance, and , prices for monovalent hepatitis B vaccines have been negotiated down to approximately $0.20–$0.40 per dose for low-income countries, reflecting and competitive bidding among manufacturers. In contrast, private sector prices in middle- and high-income markets typically range from $40–$110 per dose, resulting in a full three-dose course costing $120–$330 without insurance or subsidies. These disparities highlight economic barriers, with bulk pricing enabling routine in resource-limited settings while private costs often deter uptake among uninsured individuals. As of 2024, global coverage for the third dose stands at 84%, with birth dose coverage at 45%. The hepatitis B vaccine holds broad regulatory approval, licensed in over 190 countries and incorporated into national immunization schedules in 194 nations as of 2024. Multiple formulations, including monovalent and combination products, are prequalified by the (WHO), ensuring quality standards for procurement in international aid and humanitarian programs. This prequalification facilitates rapid deployment in emergencies and supports equitable distribution through verified supply chains. Patent expirations for early recombinant hepatitis B vaccines in the 2000s spurred the development of generic versions, dramatically reducing production costs and expanding manufacturer participation, which contributed to a price drop from $3–$6 per dose in the 1990s to under $0.50 by 2010. Despite these advances, access remains uneven due to persistent barriers in conflict-affected regions, where insecurity disrupts logistics and healthcare delivery, and in rural areas, where inadequate cold-chain infrastructure and remoteness limit outreach. To mitigate these equity gaps, initiatives like provide targeted subsidies to low- and middle-income countries, covering up to $0.80 per birth dose or $100,000 per country annually to support implementation in high-burden areas. These subsidies, integrated into broader global mechanisms such as 's transition funding for self-financing nations, prioritize vulnerable populations and aim to close affordability divides without overlapping physical supply logistics.

Brand names

The Hepatitis B vaccine is available under several brand names, each produced by specific manufacturers with formulations tailored for different age groups and indications. These recombinant vaccines contain hepatitis B surface antigen (HBsAg) adsorbed to aluminum hydroxide, except where noted, and are administered intramuscularly. Recombivax HB, manufactured by Merck & Co., is approved for use in the United States and globally. It is available in pediatric (5 mcg HBsAg per 0.5 mL dose for ages 0-19 years), adult (10 mcg HBsAg per 1 mL dose for ages 20 years and older), and dialysis (40 mcg HBsAg per 1 mL dose) formulations, typically given in a three-dose series at 0, 1, and 6 months. Engerix-B, produced by GlaxoSmithKline (GSK), is a widely used vaccine internationally, including in national immunization programs. It comes in pediatric (10 mcg HBsAg per 0.5 mL dose for ages up to 19 years) and adult (20 mcg HBsAg per 1 mL dose for ages 20 years and older) formulations, administered in a standard three-dose schedule at 0, 1, and 6 months. Heplisav-B, developed by Dynavax Technologies, is an adjuvanted vaccine approved for adults aged 18 years and older in the United States. Each 0.5 mL dose contains 20 mcg HBsAg combined with 3,000 mcg of the CpG 1018 adjuvant, given in a two-dose regimen at 0 and 1 month, offering higher seroprotection rates compared to traditional three-dose vaccines. Twinrix, also by GSK, is a combination vaccine incorporating the adult formulation of Engerix-B (20 mcg per 1 mL dose) with inactivated antigen, approved for individuals aged 18 years and older. In , Shanvac-B, manufactured by (a affiliate), is a regionally prominent recombinant vaccine prequalified by the . It is formulated as 10 mcg per 0.5 mL for pediatric use and 20 mcg per 1 mL for adults, following a three-dose schedule.

Public perceptions

Public acceptance of the Hepatitis B vaccine has generally been high within routine immunization programs in developed countries, where childhood vaccination coverage often exceeds 90%. For instance, in the WHO European Region, the third-dose coverage for the vaccine among infants reached 91% in recent estimates, reflecting strong integration into national schedules and trust in public health systems. Similarly, in the United States, coverage among children aged 19–35 months for the complete series stands at approximately 92.8% as of 2023, underscoring widespread uptake despite occasional pockets of hesitancy. However, vaccine hesitancy persists in certain communities, often fueled by debunked myths linking the vaccine—particularly the birth dose—to autism spectrum disorders, with no scientific evidence supporting such claims. Controversies surrounding the vaccine emerged prominently in the 1990s, centered on thimerosal, a mercury-containing used in some formulations, which raised public concerns about potential despite lacking evidence of harm at vaccine doses. In response, thimerosal was reduced or eliminated from most childhood vaccines in the United States and many other countries by 2001, alleviating these fears without impacting overall vaccine safety. Anti-vaccination movements have also propagated unsubstantiated links between the Hepatitis B vaccine and autoimmune diseases, such as or chronic arthritis, but extensive epidemiological studies have found no causal association. To counter misinformation and bolster confidence, the (WHO) has led global education efforts, including annual campaigns on , which emphasize the vaccine's proven safety and efficacy in preventing . These initiatives, supported by fact sheets and multimedia resources, highlight success stories from vaccination programs that have dramatically reduced prevalence worldwide. As of 2024, global coverage for the third dose stands at 84%, with birth dose coverage at 45%. Media coverage of these achievements, such as sharp declines in chronic infections among vaccinated cohorts, has further reinforced positive perceptions in many regions. Cultural factors significantly influence uptake in high-prevalence areas like and , where stigma associated with infection—often tied to misconceptions about transmission through casual contact—discourages testing and vaccination. In these communities, HBV is frequently viewed as a moral failing or hereditary , leading to and reluctance to seek preventive measures, even as global coverage lags at around 84% for the full series. Targeted community outreach has shown promise in addressing these barriers by promoting awareness without exacerbating discrimination.

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