Hepatitis B vaccine
|Target disease||Hepatitis B|
|Trade names||Recombivax HB|
|(what is this?)|
Hepatitis B vaccine is a vaccine that prevents hepatitis B. The first dose is recommended within 24 hours of birth with either two or three more doses given after that. This includes those with poor immune function such as from HIV/AIDS and those born premature. It is also recommended for health-care workers to be vaccinated. In healthy people routine immunization results in more than 95% of people being protected.
Blood testing to verify that the vaccine has worked is recommended in those at high risk. Additional doses may be needed in people with poor immune function but are not necessary for most people. In those who have been exposed to the hepatitis B virus but not immunized, hepatitis B immune globulin should be given in addition to the vaccine. The vaccine is given by injection into a muscle.
Serious side effects from the hepatitis B vaccine are very uncommon. Pain may occur at the site of injection. It is safe for use during pregnancy or while breastfeeding. It has not been linked to Guillain–Barré syndrome. The current vaccines are produced with recombinant DNA techniques. They are available both by themselves and in combination with other vaccines.
The first hepatitis B vaccine was approved in the United States in 1981. A recombinant version came to market in 1986. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. As of 2014, the wholesale cost in the developing world is US$0.58–13.20 per dose. In the United States it costs US$50–100.
Hepatitis B vaccination, hepatitis B immunoglobulin, and the combination of hepatitis B vaccine plus hepatitis B immunoglobulin, all are considered as preventive for babies born to mothers infected with HBV. The combination is superior for protecting these infants. The vaccine during pregnancy is not considered to be valuable in protecting babies of the infected mothers. Hepatitis B immunoglobulin before birth has not been well studied.
In the United States vaccination is recommended for nearly all babies at birth. Many countries now routinely vaccinate infants against hepatitis B. In countries with high rates of hepatitis B infection, vaccination of newborns has not only reduced the risk of infection, but has also led to marked reduction in 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.
In many areas, vaccination against hepatitis B is also required for all health-care and laboratory staff. Both types of the vaccine, the plasma-derived vaccine (PDV) and recombinant vaccine (RV), seems to be able to elicit similar protective anti-HBs levels.
The Centers for Disease Control and Prevention have issued recommendations for vaccination against hepatitis B among patients with diabetes mellitus. The World Health Organization recommends a pentavalent vaccine, combining vaccines against diphtheria, tetanus, pertussis and Haemophilus influenzae type B with the vaccine against hepatitis B. There is not yet sufficient evidence on how effective this pentavalent vaccine is in relation to the individual vaccines.
Following the primary course of 3 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.
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.
People who fail to respond (anti-Hbs antibody level below 10 mIU/ml) should be tested to exclude current or past Hepatitis B infection, and given a repeat course of 3 vaccinations, followed by further retesting 1–4 months after the second course. Those who still do not respond to a second course of vaccination may respond to intradermal administration or to a high dose vaccine or to a double dose of a combined hepatitis A and B vaccine. Those who still fail to respond will require hepatitis B immunoglobulin (HBIG) if later exposed to the hepatitis B virus.
Poor responses are mostly associated with being over the age of 40 years, obesity and smoking, and also in alcoholics, especially if with advanced liver disease. Patients who are immunosuppressed or on renal dialysis may respond less well and require larger or more frequent doses of vaccine. At least one study suggests that hepatitis B vaccination is less effective in patients with HIV.
Duration of protection
It is now believed that the hepatitis B vaccine provides indefinite protection. However, it was previously believed and suggested that the vaccination would only provide effective coverage of between five and seven years, 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. 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, 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 5 years after initial immunization.
Serious side effects from the hepatitis B vaccine are very uncommon. Pain may occur at the site of injection. It is generally considered safe for use, during pregnancy or while breastfeeding. It has not been linked to Guillain–Barré syndrome.
Several studies have looked for an association between recombinant hepatitis B vaccine (HBV) and multiple sclerosis (MS) in adults. Most studies do not support a causal relationship between hepatitis B vaccination and demyelinating diseases such as MS. A 2004 study reported a significant increase in risk within 3 years of vaccination. Some of these studies were criticized for methodological problems. This controversy created public misgivings about HB vaccination, and hepatitis B vaccination in children remained low in several countries. A 2006 study concluded that evidence did not support an association between HB vaccination and sudden infant death syndrome, chronic fatigue syndrome, or multiple sclerosis. A 2007 study found that the vaccination does not seem to increase the risk of a first episode of MS in childhood.
|Hepatitis B (HepB3) immunization coverage among 1-year-olds worldwide|
|Antigua and Barbuda||99|
|Bolivia (Plurinational State of)||94|
|Bosnia and Herzegovina||89|
|Central African Republic||47|
|Democratic People's Republic of Korea||93|
|Democratic Republic of the Congo||80|
|Iran (Islamic Republic of)||99|
|Lao People's Democratic Republic||88|
|Micronesia (Federated States of)||83|
|Papua New Guinea||62|
|Republic of Korea||99|
|Republic of Moldova||92|
|Saint Kitts and Nevis||98|
|Saint Vincent and the Grenadines||98|
|São Tomé and Príncipe||95|
|Syrian Arab Republic||71|
|The former Yugoslav republic of Macedonia||97|
|Trinidad and Tobago||92|
|United Arab Emirates||94|
|United Republic of Tanzania||97|
|United States of America||90|
|Venezuela (Bolivarian Republic of)||78|
The road to the hepatitis B vaccine began in 1963 when American physician/geneticist Baruch Blumberg discovered what he called the "Australia Antigen" (now called HBsAg) in the serum of an Australian Aboriginal person. In 1968, this protein was found to be part of the virus that causes "serum hepatitis" (hepatitis B) by virologist Alfred Prince. 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.
Hilleman collected blood from gay men and intravenous drug users—groups known to be at risk for viral hepatitis. This was in the late 1970s, when HIV was yet unknown to medicine. In addition to the sought-after hepatitis B surface proteins, the blood samples likely contained HIV. Hilleman devised a multistep process to purify this blood so that only the hepatitis B surface proteins remained. Every known virus was killed by this process, and Hilleman was confident that the vaccine was safe.
The first large-scale trials for the blood-derived vaccine were performed on gay men, 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. The vaccine was approved in 1981.
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. 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. This is the vaccine still in use today.
In 1976, Blumberg had 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. 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."
In 2017, a two-dose HBV vaccine for adults, HEPLISAV-B gained US FDA approval. It uses recombinant HB surface antigen, as previous vaccines, but includes a novel CpG 1018 adjuvant, a 22-mer phosphorothioate-linked oligodeoxynucleotide. It was non inferior with respect to immunogenicity.
The vaccine contains one of the viral envelope proteins, hepatitis B surface antigen (HBsAg). It is now produced by yeast cells, into which the genetic code for HBsAg has been inserted. 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.
The common brands available are Recombivax HB (Merck), Engerix-B (GSK), Elovac B (Human Biologicals Institute, a division of Indian Immunologicals Limited), Genevac B (Serum Institute), Shanvac B, etc. These vaccines are given by the intramuscular route. In late 2017 the FDA approved a new vaccine called Heplisav-B from Dynavax Technologies Corps. This two-dose vaccine will compete with Engerix-B's three-dose vaccine.
- "Hepatitis B vaccines WHO position paper" (PDF). Weekly epidemiological record. 40 (84): 405–420. 2 Oct 2009. Archived (PDF) from the original on 2015-12-02.
- Chen W, Gluud C (October 2005). "Vaccines for preventing hepatitis B in health-care workers". The Cochrane Database of Systematic Reviews (4): CD000100. doi:10.1002/14651858.CD000100.pub3. PMID 16235273.
- Moticka E. A Historical Perspective on Evidence-Based Immunology. p. 336. ISBN 9780123983756.
- "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Archived (PDF) from the original on 13 December 2016. Retrieved 8 December 2016.
- "Vaccine, Hepatitis B". International Drug Price Indicator Guide. Retrieved 6 December 2015.[permanent dead link]
- Hamilton R (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 314. ISBN 9781284057560.
- Lee C, Gong Y, Brok J, Boxall EH, Gluud C (April 2006). "Hepatitis B immunisation for newborn infants of hepatitis B surface antigen-positive mothers". The Cochrane Database of Systematic Reviews (2): CD004790. doi:10.1002/14651858.CD004790.pub2. PMID 16625613.
- Sangkomkamhang US, Lumbiganon P, Laopaiboon M (November 2014). "Hepatitis B vaccination during pregnancy for preventing infant infection". The Cochrane Database of Systematic Reviews (11): CD007879. doi:10.1002/14651858.CD007879.pub3. PMID 25385500.
- Eke AC, Eleje GU, Eke UA, Xia Y, Liu J (February 2017). "Hepatitis B immunoglobulin during pregnancy for prevention of mother-to-child transmission of hepatitis B virus". The Cochrane Database of Systematic Reviews. 2: CD008545. doi:10.1002/14651858.CD008545.pub2. PMID 28188612.
- Committee On Infectious Diseases; Committee On Fetus And Newborn (September 2017). "Elimination of Perinatal Hepatitis B: Providing the First Vaccine Dose Within 24 Hours of Birth". Pediatrics. 140 (3): e20171870. doi:10.1542/peds.2017-1870. PMID 28847980.
- Chang MH, Chen CJ, Lai MS, Hsu HM, Wu TC, Kong MS, Liang DC, Shau WY, Chen DS (June 1997). "Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group". The New England Journal of Medicine. 336 (26): 1855–9. doi:10.1056/NEJM199706263362602. PMID 9197213.
- "Hepatitis B vaccine". Nhs.uk. Archived from the original on 2017-06-28. Retrieved 2017-04-27.
- Joint Committee on Vaccination and Immunisation (2006). "Chapter 12 Immunisation of healthcare and laboratory staff—Hepatitis B" (PDF). Immunisation Against Infectious Disease 2006 ("The Green Book") (3rd ed.). Edinburgh: Stationery Office. p. 468. ISBN 0-11-322528-8.
- Centers for Disease Control and Prevention (CDC) (December 2011). "Use of hepatitis B vaccination for adults with diabetes mellitus: recommendations of the Advisory Committee on Immunization Practices (ACIP)". MMWR. Morbidity and Mortality Weekly Report. 60 (50): 1709–11. PMID 22189894.
- Bar-On ES, Goldberg E, Hellmann S, Leibovici L (April 2012). "Combined DTP-HBV-HIB vaccine versus separately administered DTP-HBV and HIB vaccines for primary prevention of diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae B (HIB)". The Cochrane Database of Systematic Reviews. 4 (4): CD005530. doi:10.1002/14651858.CD005530.pub3. PMID 22513932.
- Joint Committee on Vaccination and Immunisation (2006). "Chapter 18: Hepatitis B". Immunisation Against Infectious Disease 2006 ("The Green Book") (3rd edition (Chapter 18 revised 10 October 2007) ed.). Edinburgh: Stationery Office. p. 468. ISBN 0-11-322528-8. Archived from the original (PDF) on 7 January 2013.
- King JW, Taylor EM, Crow SD, White MC, Todd JR, Poe MB, Conrad SA, Gelder FB (1990). "Comparison of the immunogenicity of hepatitis B vaccine administered intradermally and intramuscularly". Reviews of Infectious Diseases. 12 (6): 1035–43. doi:10.1093/clinids/12.6.1035. PMID 2148433.
- Levitz RE, Cooper BW, Regan HC (February 1995). "Immunization with high-dose intradermal recombinant hepatitis B vaccine in healthcare workers who failed to respond to intramuscular vaccination". Infection Control and Hospital Epidemiology. 16 (2): 88–91. doi:10.1086/647062. PMID 7759824.
- Cardell K, Akerlind B, Sällberg M, Frydén A (August 2008). "Excellent response rate to a double dose of the combined hepatitis A and B vaccine in previous nonresponders to hepatitis B vaccine". The Journal of Infectious Diseases. 198 (3): 299–304. doi:10.1086/589722. PMID 18544037.
- Roome AJ, Walsh SJ, Cartter ML, Hadler JL (1993). "Hepatitis B vaccine responsiveness in Connecticut public safety personnel". JAMA. 270 (24): 2931–4. doi:10.1001/jama.270.24.2931. PMID 8254852.
- Rosman AS, Basu P, Galvin K, Lieber CS (September 1997). "Efficacy of a high and accelerated dose of hepatitis B vaccine in alcoholic patients: a randomized clinical trial". The American Journal of Medicine. 103 (3): 217–22. doi:10.1016/S0002-9343(97)00132-0. PMID 9316554.
- Pasricha N, Datta U, Chawla Y, Singh S, Arora SK, Sud A, Minz RW, Saikia B, Singh H, James I, Sehgal S (March 2006). "Immune responses in patients with HIV infection after vaccination with recombinant Hepatitis B virus vaccine". BMC Infectious Diseases. 6: 65. doi:10.1186/1471-2334-6-65. PMC 1525180. PMID 16571140. Cold or Flu like symptoms can develop after receiving the vaccine, but these are short lived. As with any injection, the muscle can become tender around the injection point for some time afterwards
- Krugman S, Davidson M (1987). "Hepatitis B vaccine: prospects for duration of immunity". The Yale Journal of Biology and Medicine. 60 (4): 333–9. PMC 2590237. PMID 3660859.
- Petersen KM, Bulkow LR, McMahon BJ, Zanis C, Getty M, Peters H, Parkinson AJ (July 2004). "Duration of hepatitis B immunity in low risk children receiving hepatitis B vaccinations from birth" (Free full text). The Pediatric Infectious Disease Journal. 23 (7): 650–5. doi:10.1097/01.inf.0000130952.96259.fd. PMID 15247604. Archived from the original on 2015-06-05.
- Gabbuti A, Romanò L, Blanc P, Meacci F, Amendola A, Mele A, Mazzotta F, Zanetti AR (April 2007). "Long-term immunogenicity of hepatitis B vaccination in a cohort of Italian healthy adolescents". Vaccine. 25 (16): 3129–32. doi:10.1016/j.vaccine.2007.01.045. PMID 17291637.
- "Are booster immunisations needed for lifelong hepatitis B immunity? European Consensus Group on Hepatitis B Immunity". Lancet. 355 (9203): 561–5. February 2000. doi:10.1016/S0140-6736(99)07239-6. PMID 10683019.
- Van Damme P, Van Herck K (March 2007). "A review of the long-term protection after hepatitis A and B vaccination". Travel Medicine and Infectious Disease. 5 (2): 79–84. doi:10.1016/j.tmaid.2006.04.004. PMID 17298912.
- Borgia G, Carleo MA, Gaeta GB, Gentile I (September 2012). "Hepatitis B in pregnancy". World Journal of Gastroenterology. 18 (34): 4677–83. doi:10.3748/wjg.v18.i34.4677. PMC 3442205. PMID 23002336.
- Martínez-Sernández V, Figueiras A (August 2013). "Central nervous system demyelinating diseases and recombinant hepatitis B vaccination: a critical systematic review of scientific production". Journal of Neurology. 260 (8): 1951–9. doi:10.1007/s00415-012-6716-y. PMID 23086181.
- "CDC – Hepatitis B and Multiple Sclerosis ( MS) – Vaccine Safety". cdc.gov. Archived from the original on 2009-11-10.
- Hernán MA, Jick SS, Olek MJ, Jick H (September 2004). "Recombinant hepatitis B vaccine and the risk of multiple sclerosis: a prospective study". Neurology. 63 (5): 838–42. doi:10.1212/01.WNL.0000138433.61870.82. PMID 15365133.
- Zuckerman JN (February 2006). "Protective efficacy, immunotherapeutic potential, and safety of hepatitis B vaccines". Journal of Medical Virology. 78 (2): 169–77. doi:10.1002/jmv.20524. PMID 16372285.
- Mikaeloff Y, Caridade G, Rossier M, Suissa S, Tardieu M (December 2007). "Hepatitis B vaccination and the risk of childhood-onset multiple sclerosis". Archives of Pediatrics & Adolescent Medicine. 161 (12): 1176–82. doi:10.1001/archpedi.161.12.1176. PMID 18056563.
- "Hepatitis B (HepB3) Data by country". WHO. Archived from the original on 24 June 2016. Retrieved 8 June 2016.
- Blumberg BS, Alter HJ, Visnich S (February 1965). "A "NEW" ANTIGEN IN LEUKEMIA SERA". JAMA. 191: 541–6. doi:10.1001/jama.1965.03080070025007. PMID 14239025.
- Howard, Colin; Zuckerman, Arie J. (1979). Hepatitis viruses of man. Boston: Academic Press. pp. 16–18. ISBN 0-12-782150-3.
- "World Hepatitis Day: The History of the Hepatitis B Vaccine | Planned Parenthood Advocates of Arizona". Blog.advocatesaz.org. 2012-07-26. Archived from the original on 2016-04-05. Retrieved 2017-04-27.
- Fisher LM (October 13, 1986). "Biotechnology Spotlight Now Shines On Chiron". New York Times. Archived from the original on August 26, 2017.
- Blumberg, Baruch (2002), Hepatitis B: The Hunt for a Killer Virus, Princeton: Princeton University Press.
- Offit PA (2007). Vaccinated:One Man's Quest to Defeat the World's Deadliest Diseases. New York: Smithsonian Books/Collins. pp. 135–136.
- "Profile: Biochemist Barush S. Blumberg: The Search for Extreme Life" (PDF). Scientific American: 31–32. July 2000.
- Gerlich WH (July 2013). "Medical virology of hepatitis B: how it began and where we are now". Virology Journal. 10: 239. doi:10.1186/1743-422X-10-239. PMC 3729363. PMID 23870415.
- Dynavax TechnologiesCorporation. "HEPLISAV-B [Hepatitis B Vaccine (Recombinant), Adjuvanted]" (PDF). FDA. Retrieved 27 November 2018.
- "Hepatitis B Vaccine from Merck". Archived from the original on 2010-04-21. Retrieved 2010-05-09.
- "CDC Viral Hepatitis". Atlanta, Georgia: Centers for Disease Control and Prevention. 2009-07-24. Archived from the original on 2009-10-20. Retrieved 2009-10-22.
- Grover D (9 November 2017). "Dynavax's hepatitis B vaccine gets FDA nod on third try, shares up". Thomson Reuters.