Hepatitis B vaccine

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Hepatitis B vaccine
Engerix B (Hepatitis B) vaccine.jpg
Hepatitis B pre-filled syringe
Vaccine description
Target diseaseHepatitis B virus
Trade namesRecombivax HB, Engerix-B, Heplisav-B, others
Clinical data
Main usesPrevent hepatitis B[1]
Side effectsPain at the site of injection[1]
  • AU: B2[2]
  • US: C (Risk not ruled out)[2]
Routes of
Intramuscular (IM)
External links
License data
Legal status

Hepatitis B vaccine is a vaccine that prevents hepatitis B.[1] It is given by injection, usually into muscle, but can be given under the skin in people with bleeding disorders.[6] In healthy people routine immunization results in more than 95% of people being protected.[1] Blood testing to verify that the vaccine has worked is recommended in those at high risk.[1]

The first dose is recommended within 24 hours of birth with either two or three more doses given after that.[1] This includes in those with poor immune function such as from HIV/AIDS and those born premature.[1] It is also recommended that health-care workers be vaccinated.[7] Additional doses may be needed in people with poor immune function but are not necessary for most people.[1] 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.[1]

Serious side effects from the hepatitis B vaccine are very uncommon.[1] Pain may occur at the site of injection.[1] It is safe for use during pregnancy or while breastfeeding.[1] It has not been linked to Guillain–Barré syndrome.[1] The hepatitis B vaccines are produced with recombinant DNA techniques.[1] They are available both by themselves and in combination with other vaccines.[1]

The first hepatitis B vaccine was approved in the United States in 1981.[8] It has been available since 1982.[9] A recombinant version came to market in 1986.[1] It is on the World Health Organization's List of Essential Medicines.[10] As of 2014, the wholesale cost in the developing world is US$0.58–13.20 per dose.[11] In the United States it costs US$50–100.[12]

Medical uses

Hepatitis B vaccination, hepatitis B immunoglobulin, and the combination of hepatitis B vaccine plus hepatitis B immunoglobulin, all are considered as preventive for babies born to mothers infected with hepatitis B virus (HBV).[13] The combination is superior for protecting these infants.[13] The vaccine during pregnancy is not considered to be valuable in protecting babies of the infected mothers.[14] Hepatitis B immunoglobulin before birth has not been well studied.[15]

In the United States vaccination is recommended for nearly all babies at birth.[16] Many countries now routinely vaccinate infants against hepatitis B. In countries with high rates of hepatitis B infection, vaccination of newborns has not only reduced the risk of infection, but has also led to 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.[17]

In the UK, the vaccine is offered to men who have sex with men (MSM), usually as part of a sexual health check-up. A similar situation is in operation in Ireland.[18]

In many areas, vaccination against hepatitis B is also required for all health-care and laboratory staff.[19] 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.[7]

The Centers for Disease Control and Prevention (CDC) issued recommendations for vaccination against hepatitis B among patients with diabetes mellitus.[20] 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 in relation to the individual vaccines.[21] 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).[22][23][24]


Following the primary course of three vaccinations, a blood test may be taken after an interval of 1–4 months to establish if there has been an adequate response, which is defined as an anti-hepatitis B surface antigen (anti-Hbs) antibody level above 100 mIU/ml. Such a full response occurs in about 85–90% of individuals.[25]

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.[25]

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 administration[26] or to a high dose vaccine[27] or to a double dose of a combined hepatitis A and B vaccine.[28] Those who still fail to respond will require hepatitis B immunoglobulin (HBIG) if later exposed to the hepatitis B virus.[25]

Poor responses are mostly associated with being over the age of 40 years, obesity, celiac disease, and tobacco smoking,[26][29] and also in alcoholics, especially if with advanced liver disease.[30] People who are immunosuppressed or on dialysis may not respond as well and require larger or more frequent doses of vaccine.[25] At least one study suggests that hepatitis B vaccination is less effective in patients with HIV.[31]


It is believed that the hepatitis B vaccine provides indefinite protection. However, it was previously believed and suggested that the vaccination would only provide effective coverage of between five and seven years,[32][33] but subsequently it has been appreciated that long-term immunity derives from immunological memory which outlasts the loss of antibody levels and hence subsequent testing and administration of booster doses is not required in successfully vaccinated immunocompetent individuals.[34][35] Hence with the passage of time and longer experience, protection has been shown for at least 25 years in those who showed an adequate initial response to the primary course of vaccinations,[36] and UK guidelines now 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.[25]


The defined daily dose is not established[37]

Side effects

Serious side effects from the hepatitis B vaccine are very rare.[1] Pain may occur at the site of injection.[1] It is generally considered safe for use, during pregnancy or while breastfeeding.[1][38] It has not been linked to Guillain–Barré syndrome.[1]

Multiple sclerosis

Several studies have looked for an association between recombinant hepatitis B vaccine and multiple sclerosis (MS) in adults.[39] Most studies do not support a causal relationship between hepatitis B vaccination and demyelinating diseases such as MS.[39][40][41] A 2004 study reported a significant increase in risk within three years of vaccination. Some of these studies were criticized for methodological problems.[42] This controversy created public misgivings about HB vaccination, and hepatitis B vaccination in children remained low in several countries. A 2006 study concluded that evidence did not support an association between HB vaccination and sudden infant death syndrome, chronic fatigue syndrome, or multiple sclerosis.[43] A 2007 study found that the vaccination does not seem to increase the risk of a first episode of MS in childhood.[44] Hepatitis B vaccination has not been linked to onset of autoimmune diseases in adulthood.[45]


Share of one-year-olds vaccinated against hepatitis B (HepB3), OWID.svg

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.[46]

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


In 1963, the American physician/geneticist Baruch Blumberg discovered what he called the "Australia Antigen" (now called HBsAg) in the serum of an Australian Aboriginal person.[47] In 1968, this protein was found to be part of the virus that causes "serum hepatitis" (hepatitis B) by virologist Alfred Prince.[48] 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.[49]

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.[49]

The first large-scale trials for the blood-derived vaccine were performed on gay men, in accordance with 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.[49] The vaccine was approved in 1981.[citation needed]

The blood-derived hepatitis B vaccine was withdrawn from the marketplace in 1986, when Pablo DT Valenzuela, Research Director of Chiron Corporation, succeeded in making the antigen in yeast and invented the world's first recombinant vaccine.[50] The recombinant vaccine was developed by inserting the HBV gene that codes for the surface protein into the yeast Saccharomyces cerevisiae. This allows the yeast to produce only the noninfectious surface protein, without any danger of introducing actual viral DNA into the final product.[49] This is the vaccine still in use today.[when?]

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). In 2002, Blumberg published a book, Hepatitis B: The Hunt for a Killer Virus.[51] In the book, according to Paul A. Offit—Hilleman's biographer and an accomplished vaccinologist himself—Blumberg...

... claimed that the hepatitis B vaccine was his invention. Maurice Hilleman's name is mentioned once.... Blumberg failed to mention that it was Hilleman who had figured out how to inactivate hepatitis B virus, how to kill all other possible contaminating viruses, how to completely remove every other protein found in human blood, and how to do all of this while retaining the structural integrity of the surface protein. Blumberg had identified Australia antigen, an important first step. But all of the other steps—the ones critical to making a vaccine—belonged to Hilleman. Later, Hilleman recalled, "I think that [Blumberg] deserves a lot of credit, but he doesn't want to give credit to the other guy."[52]

Robert Purcell, a virologist, has emphasized the importance of the hepatitis B vaccine; in figuring out the hepatitis viruses, generally.[53][54]

In 2017, a two-dose HBV vaccine for adults, Heplisav-B gained U.S. Food and Drug Administration (FDA) approval.[55] 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 with respect to immunogenicity.[56]


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.[57] 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 HBV infection.[58]

Brand names

The common brands available are Recombivax HB (Merck),[59] Engerix-B (GSK),[60] Elovac B (Human Biologicals Institute, a division of Indian Immunologicals Limited), Genevac B (Serum Institute), Shanvac B, Heplisav-B,[55] etc. These vaccines are given by the intramuscular route.

Twinrix (GSK) is a vaccine against hepatitis A and hepatitis B.[61][62]

Pediarix is a vaccine against diphtheria, tetanus, pertussis, hepatitis B, and poliomyelitis.[63]

Vaxelis is a vaccine against diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus influenzae type B (Meningococcal Protein Conjugate), and hepatitis B.[64][65]


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