Hepatitis B vaccine
| Vaccine description |
| Target disease |
Hepatitis B |
| Type |
Subunit |
| Clinical data |
| Trade names |
Recombivax HB |
| AHFS/Drugs.com |
Monograph |
| MedlinePlus |
a607014 |
| Identifiers |
| ATC code |
J07BC01 (WHO) |
| ChemSpider |
none |
| NY (what is this?) (verify) |
Hepatitis B vaccine is a vaccine that prevents hepatitis B.[1] 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. 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. 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.[1]
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.[1]
The first hepatitis B vaccine was approved in the United States in 1981.[2] A safer version came to market in 1986.[1] It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.[3] As of 2014, the wholesale cost in the developing world is US$0.58–13.20 per dose.[4] In the United States it costs US$50–100.[5]
Contents
- 1 Medical uses
- 1.1 Effectiveness
- 1.2 Duration of protection
- 2 Side effects
- 3 Usage
- 4 History
- 5 Manufacture
- 6 Brandnames
- 7 Research
- 8 References
- 9 External links
Medical uses
Babies born to mothers infected with HBV are vaccinated with hepatitis B vaccine and injected with hepatitis B immunoglobulin (HBIG).[6]
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.[7]
In the UK, the vaccine is offered to MSM, usually as part of a sexual health check-up. A similar situation is in operation in Ireland.[8]
In many areas, vaccination against hepatitis B is also required for all health-care and laboratory staff.[9]
The Centers for Disease Control and Prevention have issued recommendations for vaccination against hepatitis B among patients with diabetes mellitus.[10]
Effectiveness
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.[11]
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.[11]
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[12] or to a high dose vaccine[13] or to a double dose of a combined Hepatitis A and B vaccine.[14] Those who still fail to respond will require hepatitis B immunoglobulin (HBIG) if later exposed to the hepatitis B virus.[11]
Poor responses are mostly associated with being over the age of 40 years, obesity and smoking,[15] and also in alcoholics, especially if with advanced liver disease.[16] Patients who are immunosuppressed or on renal dialysis may respond less well and require larger or more frequent doses of vaccine.[11] At least one study suggests that hepatitis B vaccination is less effective in patients with HIV.[17]
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 cover of between five and seven years,[18][19] 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.[20][21] 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,[22] and UK guidelines now suggest that for initial responders who require ongoing protection, such as for healthcare workers, only a single booster is advocated at 5 years.[11]
Side effects
Several studies looked for a significant association between recombinant hepatitis B vaccine (HBV) and multiple sclerosis (MS) in adults. Most published scientific studies do not support a causal relationship between hepatitis B vaccination and demyelinating diseases such as MS.[23] A 2004 study[24] 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.[25] A 2007 study found that the vaccination does not seem to increase the risk of a first episode of MS in childhood.[26]
A 2009 study of the hepatitis B vaccine and associated risk of CNS inflammatory demyelination was conducted. The hepatitis B vaccine was found to be generally safe, however the Engerix B vaccine appeared to triple the risk of CNS inflammatory demyelination in infant boys.[27] The study was criticized for methodological errors.[28]
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.[29]
Usage
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 in 2014.[30]
| Hepatitis B (HepB3) immunization coverage among 1-year-olds worldwide |
| Country |
Coverage % |
| Afghanistan |
75 |
| Albania |
98 |
| Algeria |
95 |
| Andorra |
96 |
| Angola |
80 |
| Antigua and Barbuda |
99 |
| Argentina |
94 |
| Armenia |
93 |
| Australia |
91 |
| Austria |
83 |
| Azerbaijan |
94 |
| Bahamas |
96 |
| Bahrain |
99 |
| Bangladesh |
95 |
| Barbados |
94 |
| Belarus |
97 |
| Belgium |
98 |
| Belize |
95 |
| Benin |
70 |
| Bhutan |
99 |
| Bolivia (Plurinational State of) |
94 |
| Bosnia and Herzegovina |
89 |
| Botswana |
95 |
| Brazil |
96 |
| Brunei Darussalam |
99 |
| Bulgaria |
95 |
| Burkina Faso |
91 |
| Burundi |
95 |
| Côte d'Ivoire |
67 |
| Cabo Verde |
95 |
| Cambodia |
97 |
| Cameroon |
87 |
| Canada |
75 |
| Central African Republic |
47 |
| Chad |
46 |
| Chile |
92 |
| China |
99 |
| Colombia |
90 |
| Comoros |
80 |
| Congo |
90 |
| Cook Islands |
99 |
| Costa Rica |
91 |
| Croatia |
95 |
| Cuba |
96 |
| Cyprus |
96 |
| Czech Republic |
99 |
| Democratic People's Republic of Korea |
93 |
| Democratic Republic of the Congo |
80 |
| Djibouti |
78 |
| Dominica |
97 |
| Dominican Republic |
89 |
| Ecuador |
83 |
| Egypt |
94 |
| El Salvador |
93 |
| Equatorial Guinea |
24 |
| Eritrea |
94 |
| Estonia |
93 |
| Ethiopia |
77 |
| Fiji |
99 |
| France |
82 |
| Gabon |
70 |
| Gambia |
96 |
| Georgia |
91 |
| Germany |
87 |
| Ghana |
98 |
| Greece |
96 |
| Grenada |
97 |
| Guatemala |
73 |
| Guinea |
51 |
| Guinea-Bissau |
80 |
| Guyana |
98 |
| Haiti |
48 |
| Honduras |
85 |
| India |
70 |
| Indonesia |
78 |
| Iran (Islamic Republic of) |
99 |
| Iraq |
62 |
| Ireland |
95 |
| Israel |
97 |
| Italy |
94 |
| Jamaica |
92 |
| Jordan |
98 |
| Kazakhstan |
95 |
| Kenya |
81 |
| Kiribati |
75 |
| Kuwait |
96 |
| Kyrgyzstan |
96 |
| Lao People's Democratic Republic |
88 |
| Latvia |
92 |
| Lebanon |
81 |
| Lesotho |
96 |
| Liberia |
50 |
| Libya |
94 |
| Lithuania |
94 |
| Luxembourg |
94 |
| Madagascar |
73 |
| Malawi |
91 |
| Malaysia |
96 |
| Maldives |
99 |
| Mali |
77 |
| Malta |
90 |
| Marshall Islands |
79 |
| Mauritania |
84 |
| Mauritius |
97 |
| Mexico |
84 |
| Micronesia (Federated States of) |
83 |
| Monaco |
99 |
| Mongolia |
99 |
| Montenegro |
87 |
| Morocco |
99 |
| Mozambique |
78 |
| Myanmar |
75 |
| Namibia |
88 |
| Nauru |
95 |
| Nepal |
92 |
| Netherlands |
95 |
| New Zealand |
93 |
| Nicaragua |
98 |
| Niger |
68 |
| Nigeria |
66 |
| Niue |
99 |
| Oman |
98 |
| Pakistan |
73 |
| Palau |
99 |
| Panama |
80 |
| Papua New Guinea |
62 |
| Paraguay |
87 |
| Peru |
88 |
| Philippines |
79 |
| Poland |
96 |
| Portugal |
98 |
| Qatar |
99 |
| Republic of Korea |
99 |
| Republic of Moldova |
92 |
| Romania |
94 |
| Russian Federation |
97 |
| Rwanda |
99 |
| Saint Kitts and Nevis |
98 |
| Saint Lucia |
99 |
| Saint Vincent and the Grenadines |
98 |
| Samoa |
91 |
| San Marino |
80 |
| São Tomé and Príncipe |
95 |
| Saudi Arabia |
98 |
| Senegal |
89 |
| Serbia |
92 |
| Seychelles |
99 |
| Sierra Leone |
83 |
| Singapore |
97 |
| Slovakia |
97 |
| Solomon Islands |
88 |
| Somalia |
42 |
| South Africa |
74 |
| Spain |
96 |
| Sri Lanka |
99 |
| Sudan |
94 |
| Suriname |
85 |
| Swaziland |
98 |
| Sweden |
42 |
| Syrian Arab Republic |
71 |
| Tajikistan |
97 |
| Thailand |
99 |
| The former Yugoslav republic of Macedonia |
97 |
| Timor-Leste |
77 |
| Togo |
87 |
| Tonga |
82 |
| Trinidad and Tobago |
92 |
| Tunisia |
98 |
| Turkey |
96 |
| Turkmenistan |
97 |
| Tuvalu |
90 |
| Uganda |
78 |
| Ukraine |
46 |
| United Arab Emirates |
94 |
| United Republic of Tanzania |
97 |
| United States of America |
90 |
| Uruguay |
95 |
| Uzbekistan |
99 |
| Vanuatu |
64 |
| Venezuela (Bolivarian Republic of) |
78 |
| Viet Nam |
95 |
| Yemen |
88 |
| Zambia |
86 |
| Zimbabwe |
91 |
History
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.[31] In 1968, this protein was found to be part of the virus that causes "serum hepatitis" (hepatitis B) by virologist Alfred Prince.[32] 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.[33]
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.[33]
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.[33] 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.[34] 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.[33] 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.[35] 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."[36]
Manufacture
The vaccine contains one of the viral envelope proteins, hepatitis B surface antigen (HBsAg). It now produced by yeast cells, into which the genetic code for HBsAg has been inserted.[37] 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.[38]
Brandnames
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.
Research
Injectable Hepatitis B vaccines require expensive production processes and refrigeration, which can make them difficult to access in developing countries. As a result, researchers have been working to engineer plants capable of producing the ingredients necessary to make vaccines so that people can eat these plants to receive the vaccine. Potatoes, bananas, lettuce, carrots, tobacco are some of the plants being genetically engineered to produce the Hepatitis B vaccine ingredients.
The process of genetically engineering plants to produce the vaccine includes extracting the gene that codes for Hepatitis B surface antigens from the Hepatitis B genome, and placing it in a bacterial plasmid. The bacteria then infect a plant, which will produce the surface antigens. When a human eats the plant, their body is stimulated to produce an antibody response to the surface antigens. Although concerns remain in improving the efficacy of edible vaccines, controlling the dosage of vaccine in each plant, and managing land allocation for this process, scientists consider this a promising avenue for vaccinating underprivileged areas of the world.
References
- ^ a b c d e "Hepatitis B vaccines WHO position paper" (PDF). Weekly epidemiological record. 40 (84): 405–420. 2 Oct 2009.
- ^ Moticka, Edward. A Historical Perspective on Evidence-Based Immunology. p. 336. ISBN 9780123983756.
- ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
- ^ "Vaccine, Hepatitis B". International Drug Price Indicator Guide. Retrieved 6 December 2015.
- ^ Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 314. ISBN 9781284057560.
- ^ Mast, E. E.; Margolis, H. S.; Fiore, A. E.; Brink, E. W.; Goldstein, S. T.; Wang, S. A.; Moyer, L. A.; Bell, B. P.; Alter, M. J.; Advisory Committee on Immunization Practices (ACIP) (2005). "A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents" (Free full text). MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 54 (RR–16): 1–31. PMID 16371945.
- ^ Chang, M. -H.; Chen, C. -J.; Lai, M. -S.; Hsu, H. -M.; Wu, T. -C.; Kong, M. -S.; Liang, D. -C.; Shau, W. -Y.; Chen, D. -S. (1997). "Universal Hepatitis B Vaccination in Taiwan and the Incidence of Hepatocellular Carcinoma in Children". New England Journal of Medicine. 336 (26): 1855–1859. doi:10.1056/NEJM199706263362602. PMID 9197213.
- ^ "Hepatitis B vaccine". www.nhs.uk.
- ^ Joint Committee on Vaccination and Immunisation (2006). "Chapter 12 Immunisation of healthcare and laboratory staff—Hepatitis B". Immunisation Against Infectious Disease 2006 ("The Green Book") (PDF) (3rd ed.). Edinburgh: Stationery Office. p. 468. ISBN 0-11-322528-8.
- ^ Centers for Disease Control and Prevention (CDC) (2011). "Use of hepatitis B vaccination for adults with diabetes mellitus: recommendations of the Advisory Committee on Immunization Practices (ACIP).". MMWR Morb Mortal Wkly Rep. 60 (50): 1709–11. PMID 22189894.
- ^ a b c d e Joint Committee on Vaccination and Immunisation (2006). "Chapter 18 Hepatitis B". Immunisation Against Infectious Disease 2006 ("The Green Book") (PDF) (3rd edition (Chapter 18 revised 10 October 2007) ed.). Edinburgh: Stationery Office. p. 468. ISBN 0-11-322528-8.
- ^ King; Taylor, E. M.; Crow, S. D.; White, M. C.; Todd, J. R.; Poe, M. B.; Conrad, S. A.; Gelder, F. B. (1990). "Comparison of the immunogenicity of hepatitis B vaccine administered intradermally and intramuscularly". Reviews of infectious diseases. 12 (6): 1035–1043. doi:10.1093/clinids/12.6.1035. PMID 2148433.
- ^ Levitz; Cooper, B.; Regan, H. (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.; Åkerlind, B.; Sällberg, M.; Frydén, A. (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): 299–226. doi:10.1086/589722. PMID 18544037.
- ^ Roome, A. J.; Walsh, S.; Cartter, M.; Hadler, J. (1993). "Hepatitis B vaccine responsiveness in Connecticut public safety personnel". Journal of the American Medical Association. 270 (24): 2931–2934. doi:10.1001/jama.270.24.2931. PMID 8254852.
- ^ Rosman, Md, A.; Basu, P.; Galvin, K.; Lieber, C. (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): 217–222. doi:10.1016/S0002-9343(97)00132-0. PMID 9316554.
- ^ Pasricha, N.; Datta, U.; Chawla, Y.; Singh, S.; Arora, S.; Sud, A.; Minz, R.; Saikia, B.; Singh, H.; James, I.; Sehgal, S. (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; Davidson, M. (1987). "Hepatitis B vaccine: prospects for duration of immunity". The Yale Journal of Biology and Medicine. 60 (4): 333–339. PMC 2590237. PMID 3660859.
- ^ Petersen, K. M.; Bulkow, L. R.; McMahon, B. J.; Zanis, C.; Getty, M.; Peters, H.; Parkinson, A. J. (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): 650–655. doi:10.1097/01.inf.0000130952.96259.fd. PMID 15247604.
- ^ Gabbuti, A.; Romanò, L.; Blanc, P.; Meacci, F.; Amendola, A.; Mele, A.; Mazzotta, F.; Zanetti, A. R. (2007). "Long-term immunogenicity of hepatitis B vaccination in a cohort of Italian healthy adolescents". Vaccine. 25 (16): 3129–3132. doi:10.1016/j.vaccine.2007.01.045. PMID 17291637.
- ^ "Are booster immunisations needed for lifelong hepatitis B immunity?". The Lancet. 355 (9203): 561–565. 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 Med Infect Dis. 5 (2): 79–84. doi:10.1016/j.tmaid.2006.04.004. PMID 17298912.
- ^ "CDC - Hepatitis B and Multiple Sclerosis ( MS) - Vaccine Safety". cdc.gov.
- ^ Hernán; Jick, S. S.; Olek, M. J.; Jick, H. (2004). "Recombinant hepatitis B vaccine and the risk of multiple sclerosis: a prospective study". Neurology. 63 (5): 838–842. doi:10.1212/01.WNL.0000138433.61870.82. PMID 15365133.
- ^ Zuckerman, J. N. (2006). "Protective efficacy, immunotherapeutic potential, and safety of hepatitis B vaccines". Journal of Medical Virology. 78 (2): 169–177. doi:10.1002/jmv.20524. PMID 16372285.
- ^ Mikaeloff, Y.; Caridade, G.; Rossier, M.; Suissa, S.; Tardieu, M. (2007). "Hepatitis B Vaccination and the Risk of Childhood-Onset Multiple Sclerosis". Archives of Pediatrics & Adolescent Medicine. 161 (12): 1176–1182. doi:10.1001/archpedi.161.12.1176. PMID 18056563.
- ^ "Hepatitis B vaccine and the risk of CNS inflammatory demyelination in childhood". Neurology. 2009.
- ^ "Global Advisory Committee on Vaccine Safety: response to the paper (in press) by Y. Mikaeloff and colleagues in Neurology entitled "Hepatitis B vaccine and the risk of CNS inflammatory demyelination in childhood"". World Health Organization. 2008.
- ^ Bar-On ES, Goldberg E, Hellmann S, Leibovici L (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)". Cochrane Database Syst Rev (4): CD005530. doi:10.1002/14651858.CD005530.pub3. PMID 22513932.
- ^ "Hepatitis B (HepB3) Data by country". WHO. Retrieved 8 June 2016.
- ^ Blumberg B, Alter H (1965). "A "new" antigen in leukemia sera". JAMA. 191: 101–106. 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.
- ^ a b c d "World Hepatitis Day: The History of the Hepatitis B Vaccine" [Planned Parenthood Advocates of Arizona], 26 July 2012, http://blog.advocatesaz.org/2012/07/26/world-hepatitis-day-the-history-of-the-hepatitis-b-vaccine/
- ^ Fisher, Lawrence M. (October 13, 1986). "Biotechnology Spotlight Now Shines On Chiron". New York Times.
- ^ Blumberg, Baruch (2002), Hepatitis B: The Hunt for a Killer Virus, Princeton: Princeton University Press.
- ^ Offit, Paul A. (2007). Vaccinated:One Man's Quest to Defeat the World's Deadliest Diseases. New York: Smithsonian Books/Collins, pp 135-136. .
- ^ "Hepatitis B Vaccine from Merck". Retrieved 2010-05-09.
- ^ "CDC Viral Hepatitis". Atlanta, Georgia: Centers for Disease Control and Prevention. 2009-07-24. Retrieved 2009-10-22.
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Tomato
|
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Cotton
|
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Other
|
- Apple
- Arabidopsis
- Brinjal
- Canola
- Papaya
- Rose
- SmartStax
- Sugar beet
- Tobacco
- Trees
- Wheat
|
|
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|
Mammals
|
- Mouse
- Enviropig
- Herman the Bull
- Knockout rat
|
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Other animals
|
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Bacteria
and viruses
|
- Ice-minus bacteria
- Hepatitis B vaccine
- Oncolytic virus
|
|
|
| Processes |
|
Inserting DNA
|
- Agrobacteria
- Biolistics
- Electroporation
- Genetic transduction
- Lipofection
- Microinjection
- Transfection
|
|
|
Types
|
- Recombinant DNA
- Transgenesis
- Cisgenesis
|
|
|
| Uses |
|
In agriculture
|
- Genetically modified food
- Pharming
- Companies
- BASF
- Bayer
- Dow AgroSciences
- DuPont Pioneer
- Monsanto
- Syngenta
|
|
|
In humans and
diagnostics
|
- Gene therapy
- Genetic enhancement
|
|
|
In research
|
- Gene knockout
- Gene knockdown
- Gene targeting
|
|
|
Related
articles |
- Transgene
- Detection of genetically modified organisms
- Genetic pollution
- Genetic engineering in fiction
- Human enhancement
- Reverse transfection
- Transhumanism
|
|
| Regulation |
- Regulation of the release of GMOs
- Regulation of GMOs in the European Union
- Regulation of GMOs in Switzerland
- Cartagena Protocol on Biosafety
|
|
| Geography |
|
|
| Similar fields |
- Synthetic biology
- Cloning
- Stem cell research
|
|
- Biology
- Genetics
- Biotechnology
- Bioethics
|