Protective efficacy, immunotherapeutic potential, and safety of hepatitis B vaccines
Hepatitis B vaccines are highly effective and safe and have been incorporated into national immunization programs in over 150 countries. The major humoral immune response is to the common a determinant of the surface antigen protein of the virus. Approximately 5–10% of healthy immunocompetent subjec...
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Published in | Journal of medical virology Vol. 78; no. 2; pp. 169 - 177 |
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Main Author | |
Format | Journal Article |
Language | English |
Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01.02.2006
Wiley-Liss |
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Abstract | Hepatitis B vaccines are highly effective and safe and have been incorporated into national immunization programs in over 150 countries. The major humoral immune response is to the common a determinant of the surface antigen protein of the virus. Approximately 5–10% of healthy immunocompetent subjects do not mount an antibody response (anti‐HBs). Non‐response is associated with different HLA‐DR alleles and impaired Th cell response, among other factors such as route of injection, age, gender, body mass, and other factors. Important hepatitis B surface antigen variants have also been identified, which may have a potential impact on immunization and routine screening of blood, blood products and tissues, and organs for transplantation. Strategies for hepatitis B immunization are reviewed. Over 1,000 million doses of hepatitis B vaccine have been used with an outstanding record of safety. There is no evidence of an association between hepatitis B vaccines and the sudden infant death syndrome, chronic fatigue syndrome, and multiple sclerosis (MS). Several studies are in progress on treatment of chronic hepatitis B infection by immunization with multiple antigenic components, combination of vaccine with antiviral drugs and cytokines, T cell vaccines, DNA vaccines alone or with DNA encoded immunomodulatory cytokines, and direct genetic manipulation of antigen presenting cells. J. Med. Virol. 78:169–177, 2006. © 2005 Wiley‐Liss, Inc. |
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AbstractList | Hepatitis B vaccines are highly effective and safe and have been incorporated into national immunization programs in over 150 countries. The major humoral immune response is to the common a determinant of the surface antigen protein of the virus. Approximately 5-10% of healthy immunocompetent subjects do not mount an antibody response (anti-HBs). Non-response is associated with different HLA-DR alleles and impaired Th cell response, among other factors such as route of injection, age, gender, body mass, and other factors. Important hepatitis B surface antigen variants have also been identified, which may have a potential impact on immunization and routine screening of blood, blood products and tissues, and organs for transplantation. Strategies for hepatitis B immunization are reviewed. Over 1,000 million doses of hepatitis B vaccine have been used with an outstanding record of safety. There is no evidence of an association between hepatitis B vaccines and the sudden infant death syndrome, chronic fatigue syndrome, and multiple sclerosis (MS). Several studies are in progress on treatment of chronic hepatitis B infection by immunization with multiple antigenic components, combination of vaccine with antiviral drugs and cytokines, T cell vaccines, DNA vaccines alone or with DNA encoded immunomodulatory cytokines, and direct genetic manipulation of antigen presenting cells. Hepatitis B vaccines are highly effective and safe and have been incorporated into national immunization programs in over 150 countries. The major humoral immune response is to the common a determinant of the surface antigen protein of the virus. Approximately 5–10% of healthy immunocompetent subjects do not mount an antibody response (anti‐HBs). Non‐response is associated with different HLA‐DR alleles and impaired Th cell response, among other factors such as route of injection, age, gender, body mass, and other factors. Important hepatitis B surface antigen variants have also been identified, which may have a potential impact on immunization and routine screening of blood, blood products and tissues, and organs for transplantation. Strategies for hepatitis B immunization are reviewed. Over 1,000 million doses of hepatitis B vaccine have been used with an outstanding record of safety. There is no evidence of an association between hepatitis B vaccines and the sudden infant death syndrome, chronic fatigue syndrome, and multiple sclerosis (MS). Several studies are in progress on treatment of chronic hepatitis B infection by immunization with multiple antigenic components, combination of vaccine with antiviral drugs and cytokines, T cell vaccines, DNA vaccines alone or with DNA encoded immunomodulatory cytokines, and direct genetic manipulation of antigen presenting cells. J. Med. Virol. 78:169–177, 2006. © 2005 Wiley‐Liss, Inc. Hepatitis B vaccines are highly effective and safe and have been incorporated into national immunization programs in over 150 countries. The major humoral immune response is to the common a determinant of the surface antigen protein of the virus. Approximately 5-10% of healthy immunocompetent subjects do not mount an antibody response (anti-HBs). Non-response is associated with different HLA-DR alleles and impaired Th cell response, among other factors such as route of injection, age, gender, body mass, and other factors. Important hepatitis B surface antigen variants have also been identified, which may have a potential impact on immunization and routine screening of blood, blood products and tissues, and organs for transplantation. Strategies for hepatitis B immunization are reviewed. Over 1,000 million doses of hepatitis B vaccine have been used with an outstanding record of safety. There is no evidence of an association between hepatitis B vaccines and the sudden infant death syndrome, chronic fatigue syndrome, and multiple sclerosis (MS). Several studies are in progress on treatment of chronic hepatitis B infection by immunization with multiple antigenic components, combination of vaccine with antiviral drugs and cytokines, T cell vaccines, DNA vaccines alone or with DNA encoded immunomodulatory cytokines, and direct genetic manipulation of antigen presenting cells. J. Med. Virol. 78:169-177, 2006. Hepatitis B vaccines are highly effective and safe and have been incorporated into national immunization programs in over 150 countries. The major humoral immune response is to the common a determinant of the surface antigen protein of the virus. Approximately 5-10% of healthy immunocompetent subjects do not mount an antibody response (anti-HBs). Non-response is associated with different HLA-DR alleles and impaired Th cell response, among other factors such as route of injection, age, gender, body mass, and other factors. Important hepatitis B surface antigen variants have also been identified, which may have a potential impact on immunization and routine screening of blood, blood products and tissues, and organs for transplantation. Strategies for hepatitis B immunization are reviewed. Over 1,000 million doses of hepatitis B vaccine have been used with an outstanding record of safety. There is no evidence of an association between hepatitis B vaccines and the sudden infant death syndrome, chronic fatigue syndrome, and multiple sclerosis (MS). Several studies are in progress on treatment of chronic hepatitis B infection by immunization with multiple antigenic components, combination of vaccine with antiviral drugs and cytokines, T cell vaccines, DNA vaccines alone or with DNA encoded immunomodulatory cytokines, and direct genetic manipulation of antigen presenting cells.Hepatitis B vaccines are highly effective and safe and have been incorporated into national immunization programs in over 150 countries. The major humoral immune response is to the common a determinant of the surface antigen protein of the virus. Approximately 5-10% of healthy immunocompetent subjects do not mount an antibody response (anti-HBs). Non-response is associated with different HLA-DR alleles and impaired Th cell response, among other factors such as route of injection, age, gender, body mass, and other factors. Important hepatitis B surface antigen variants have also been identified, which may have a potential impact on immunization and routine screening of blood, blood products and tissues, and organs for transplantation. Strategies for hepatitis B immunization are reviewed. Over 1,000 million doses of hepatitis B vaccine have been used with an outstanding record of safety. There is no evidence of an association between hepatitis B vaccines and the sudden infant death syndrome, chronic fatigue syndrome, and multiple sclerosis (MS). Several studies are in progress on treatment of chronic hepatitis B infection by immunization with multiple antigenic components, combination of vaccine with antiviral drugs and cytokines, T cell vaccines, DNA vaccines alone or with DNA encoded immunomodulatory cytokines, and direct genetic manipulation of antigen presenting cells. |
Author | Zuckerman, Jane N. |
Author_xml | – sequence: 1 givenname: Jane N. surname: Zuckerman fullname: Zuckerman, Jane N. email: j.zuckerman@medsch.ucl.ac.uk organization: Academic Centre for Travel Medicine and Vaccines and the WHO Collaborating Centre for Reference, Research and Training in Travel Medicine, Royal Free and University College Medical School, University College London, London, United Kingdom |
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Keywords | Immune response Toxicity Orthohepadnavirus Hepatic disease DNA vaccines Genetic vaccine Infection Virus Viral hepatitis B Hepadnaviridae Efficiency Viral disease Immunotherapy HBV mutants hepatitis B vaccines safety Digestive diseases Mutation Hepatitis B virus |
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Heathcote J, McHutchinson J, Lee S, Tong M, Reener K, Minuk G, Wright T, Fikes J, Livingston B, Settie A, Chestnut R. 1999. A pilot study of the CY-T cell vaccine in subjects chronically infected with hepatitis B virus. The CY 1999 T Cell vaccine Study Group. Hepatology 30: 531-536. Hernan MA, Jick SS, Olek MJ, Jick H. 2004. Recombinant hepatitis B vaccine and the risk of multiple sclerosis. Neurology 63: 838-842. Canada Communicable Disease Report. 1992. Adverse events following the administration of hepatitis B vaccines. Can Commun Dis Rep 18-7: 49-53. Hsu HY, Chang MH, Liaw SH, Ni YH, Chen HL. 1999. Changes of hepatitis B surface antigen variants in carrier children before and after universal vaccination in Taiwan. Hepatology 30: 1312-1317. Oon C-J, Lim G-K, Zaho Y, Goh K-T, Tan K-L, Yo S-L, Hopes E, Harrison TJ, Zuckerman AJ. 1995. Molecular epidemiology of hepatitis B virus vaccine variants in Singapore. Vaccine 13: 699-702. Carman WF, Zanetti AR, Karayiannis P, Waters J, Manzillo G, Tanzi E, Zuckerman AJ, Thomas HC. 1990. Vaccine-induced escape mutant of hepatitis B virus. Lancet 336: 325-329. Jarrosson L, Kolopp-Sarda MN, Aguillar P, Bene MC, Faure GC, Kohler C. 2004. Most humoral non-responders to hepatitis B vaccines develop HBV-specific cellular immune responses. Vaccine 22: 3789-3796. Jefferson T. 1998. Vaccination and its adverse effects: Real or perceived. Brit Med J 317: 159-160. Autram B, Carcelain G, Combadiere B, Debre P. 2004. Therapeutic vaccines for chronic infections. Science 305: 205-208. Gout O, Lyon-Caen O. 1998. Sclerotic plaques and vaccination against hepatitis B. Rev Neurol (Paris) 154: 205-207. Gonclaves L, Albarrar B, Salmen S, Borges L, Fields H, Montes H, Soyano A, Diaz Y, Berruta L. 2004. The non-response to hepatitis B vaccination is associated with impaired lymphocyte activation. Virology 326: 20-28. Canada Medical Association. 1993. Report of the working group on the possible relationship between hepatitis B vaccination and the chronic fatigue syndrome. Can Med Assoc J 149: 314-316. Zuckerman JN, Zuckerman AJ. 1998. Is there a need for boosters of hepatitis B vaccines? Viral Hepatitis Rev 4: 43-46. Zuckerman JN, Cockcroft A, Zuckerman AJ. 1992. Site of injection for vaccination. Brit Med J 305: 1158-1159. Confavreux C, Suissa S, Saddier P, Bourdes V, Vukusic S. 2001. Vaccinations and the risk of relapse in multiple sclerosis. New Eng J Med 344: 319-326. Wilson JN, Nokes DJ, Carman WF. 1999. The predicted pattern of emergence of vaccine-resistant hepatitis B: A cause for concern? Vaccine 17: 973-978. Michel M-L, Pol S, Brechot C, Tiollais P. 2001. Immunotherapy of chronic hepatitis B by anti-HBV vaccine: From present to future. Vaccine 19: 2395-2399. Krusall MS, Alper CA, Awdeh Z, Yunis EJ, Marcus-Bagley D. 1992. The immune response to hepatitis B vaccine in humans: Inheritance patterns in families. J Exp Med 175: 495-502. Wraith DC, Goldman M, Lambert P-H. 2003. Vaccination and autoimmune disease: What is the evidence? Lancet 362: 1659-1666. Ascherio A, Zhnag SM, Herbab MA, Olek MJ, Coplan PM, Brodovicz K, walker AM. 2001. Hepatitis B vaccination and the risk of multiple sclerosis. New Eng J Med 344: 327-332. European Consensus Group on Hepatitis B Immunity. 2002. Are booster immunisations needed for lifelong hepatitis B immunity? Lancet 355: 561-565. Tourbah A, Gout O, Liblau R, Lyon-Caen O, Bougniot C, Iba-Zizen Cabanis EA. 1999. Encephalitis after hepatitis B vaccination: Recurrent disseminated encephalitis or MS? Neurology 53: 396-401. Milich DR, McLachlan A, Chisari FV, Kent SB, Thornton GB. 1986. Immune response to the pre-S1 region of hepatitis B surface antigen: A pre-S1-specific T cell response can bypass non-responsiveness to the pre-S2 and S regions of HbsAg. J Immunol 137: 315-322. Whittle H, Jaffar S, Warnsborough M, Mendy M, Dumpis U, Collinson A, Hall XX. 2002. Observational study of vaccine efficacy 14 years after trial of hepatitis B vaccination in Gambian children. Brit Med J 325: 569-572. McDermott AB, Cohen SBA, Zuckerman JN, Madrigal J. 1999. Human leukocyte antigens influence the immune response to a pre-S1, pre-S2, S hepatitis B vaccine. Vaccine 17: 330-339. 2004; 22 2001; 344 2004; 63 1986; 137 2002; 12 2002; 355 1995; 13 1998; 317 1996; 50 2002; 1 1997 1996 1992; 305 1998; 154 2004; 305 1993; 149 2004; 326 1996; 348 1999 1990; 336 1992; 18‐7 1989; 321 1992; 175 1999; 17 2002; 68 2002; 66 1999; 58 2001; 19 2002; 325 1999; 53 1999; 30 1999; 72 1998; 4 2003; 362 1988 Heathcote (10.1002/jmv.20524-BIB16) 1999; 30 Canada Medical Association (10.1002/jmv.20524-BIB8) 1993; 149 Tourbah (10.1002/jmv.20524-BIB30) 1999; 53 Gout (10.1002/jmv.20524-BIB15) 1998; 154 Arif (10.1002/jmv.20524-BIB2) 1988 Beckebaum (10.1002/jmv.20524-BIB6) 2002; 12 Confavreux (10.1002/jmv.20524-BIB10) 2001; 344 Zuckerman (10.1002/jmv.20524-BIB38) 2002; 1 Canada Communicable Disease Report (10.1002/jmv.20524-BIB7) 1992; 18-7 Zuckerman (10.1002/jmv.20524-BIB36) 1998; 4 Banatvala (10.1002/jmv.20524-BIB5) 1996 European Consensus Group on Hepatitis B Immunity (10.1002/jmv.20524-BIB12) 2002; 355 Hsu (10.1002/jmv.20524-BIB18) 1999; 30 Jefferson (10.1002/jmv.20524-BIB20) 1998; 317 Margolis (10.1002/jmv.20524-BIB22) 1999 Nainan (10.1002/jmv.20524-BIB27) 2002; 68 Zuckerman (10.1002/jmv.20524-BIB37) 1999; 58 McDermott (10.1002/jmv.20524-BIB23) 1999; 17 Wraith (10.1002/jmv.20524-BIB34) 2003; 362 Alper (10.1002/jmv.20524-BIB1) 1989; 321 Hernan (10.1002/jmv.20524-BIB17) 2004; 63 Francois (10.1002/jmv.20524-BIB13) 2001; 19 Jarrosson (10.1002/jmv.20524-BIB19) 2004; 22 WER (10.1002/jmv.20524-BIB31) 1999; 72 Zuckerman (10.1002/jmv.20524-BIB35) 1996; 50 Carman (10.1002/jmv.20524-BIB9) 1990; 336 Krusall (10.1002/jmv.20524-BIB21) 1992; 175 Whittle (10.1002/jmv.20524-BIB32) 2002; 325 Gonclaves (10.1002/jmv.20524-BIB14) 2004; 326 Oon (10.1002/jmv.20524-BIB28) 1995; 13 Michel (10.1002/jmv.20524-BIB24) 2001; 19 Oon (10.1002/jmv.20524-BIB29) 1996; 348 Ascherio (10.1002/jmv.20524-BIB3) 2001; 344 Milich (10.1002/jmv.20524-BIB25) 1986; 137 Nainan (10.1002/jmv.20524-BIB26) 1997 Wilson (10.1002/jmv.20524-BIB33) 1999; 17 Zuckerman (10.1002/jmv.20524-BIB39) 1992; 305 Autram (10.1002/jmv.20524-BIB4) 2004; 305 Dahmen (10.1002/jmv.20524-BIB11) 2002; 66 |
References_xml | – reference: Heathcote J, McHutchinson J, Lee S, Tong M, Reener K, Minuk G, Wright T, Fikes J, Livingston B, Settie A, Chestnut R. 1999. A pilot study of the CY-T cell vaccine in subjects chronically infected with hepatitis B virus. The CY 1999 T Cell vaccine Study Group. Hepatology 30: 531-536. – reference: Zuckerman JN. 1996. Non-response to hepatitis B vaccines and the kinetics of anti-HBs production. J Med Virol 50: 283-288. – reference: McDermott AB, Cohen SBA, Zuckerman JN, Madrigal J. 1999. Human leukocyte antigens influence the immune response to a pre-S1, pre-S2, S hepatitis B vaccine. Vaccine 17: 330-339. – reference: Wilson JN, Nokes DJ, Carman WF. 1999. The predicted pattern of emergence of vaccine-resistant hepatitis B: A cause for concern? Vaccine 17: 973-978. – reference: Francois G, Kew M, Van Damme P, Mphahled J, Meheus A. 2001. Mutant hepatitis B viruses: A matter of academic interest only or a problem with far-reaching implications? Vaccine 19: 3799-3815. – reference: Hernan MA, Jick SS, Olek MJ, Jick H. 2004. Recombinant hepatitis B vaccine and the risk of multiple sclerosis. Neurology 63: 838-842. – reference: Zuckerman JN, Zuckerman AJ. 1998. Is there a need for boosters of hepatitis B vaccines? Viral Hepatitis Rev 4: 43-46. – reference: Banatvala JE, Boxall E, Heptonstall J, Zuckerman AJ. 1996. Immunisation strategies: Proposal drafted in London and reviewed in prevention of hepatitis B in the newborn, children and adolescents. London: Royal Coll Physicians. pp 1-113. – reference: Zuckerman AJ, Zuckerman JN. 1999. Molecular epidemiology of hepatitis B virus mutants. J Med Virol 58: 193-195. – reference: Whittle H, Jaffar S, Warnsborough M, Mendy M, Dumpis U, Collinson A, Hall XX. 2002. Observational study of vaccine efficacy 14 years after trial of hepatitis B vaccination in Gambian children. Brit Med J 325: 569-572. – reference: Wraith DC, Goldman M, Lambert P-H. 2003. Vaccination and autoimmune disease: What is the evidence? Lancet 362: 1659-1666. – reference: Gout O, Lyon-Caen O. 1998. Sclerotic plaques and vaccination against hepatitis B. Rev Neurol (Paris) 154: 205-207. – reference: Oon C-J, Tan K-L, Harrison TJ, Zuckerman AJ. 1996. Natural history of hepatitis B surface antigen mutants in children. Lancet 348: 1524. – reference: Alper CA, Kruksall MS, Marcus_Bagley D, Craven DE, Katz AJ, Brink SJ, Dienstag JL, Awdeh Z, Yunis EJ. 1989. Genetic prediction of non-response to hepatitis B vaccine. New Eng J Med 321: 708-712. – reference: WER. 1999. Expanded Programme on Immunisation (EPI). Lack of evidence that hepatitis B vaccine causes multiple sclerosis. Wkly Epidemiol Rec 72: 149-152. – reference: Michel M-L, Pol S, Brechot C, Tiollais P. 2001. Immunotherapy of chronic hepatitis B by anti-HBV vaccine: From present to future. Vaccine 19: 2395-2399. – reference: Dahmen A, Herzog-Hauff S, Bocher WO, Galle PR, Lohr HF. 2002. Clinical and immunological efficacy of intradermal vaccine plus lamivudine with or without interleukin-2 in patients with chronic hepatitis B. J Med Virol 66: 452-460. – reference: Beckebaum S, Cicinnati VR, Gerken G. 2002. DNA-based immunotherapy: Potential for the treatment of chronic viral hepatitis? Rev Med Virol 12: 297-319. – reference: European Consensus Group on Hepatitis B Immunity. 2002. Are booster immunisations needed for lifelong hepatitis B immunity? Lancet 355: 561-565. – reference: Nainan OV, Khristova ML, Byun K, Xia G, Taylor PE, Stevens CE, Margolis HS. 2002. Genetic variation of hepatitis B surface antigen coding region among infants with chronic hepatitis B virus infection. J Med Virol 68: 319-327. – reference: Zuckerman JN, Zuckerman AJ. 2002. Recombinant hepatitis B triple antigen vaccine: Hepacare™. Expert Rev Vaccine 1: 141-144. – reference: Zuckerman JN, Cockcroft A, Zuckerman AJ. 1992. Site of injection for vaccination. Brit Med J 305: 1158-1159. – reference: Tourbah A, Gout O, Liblau R, Lyon-Caen O, Bougniot C, Iba-Zizen Cabanis EA. 1999. Encephalitis after hepatitis B vaccination: Recurrent disseminated encephalitis or MS? Neurology 53: 396-401. – reference: Krusall MS, Alper CA, Awdeh Z, Yunis EJ, Marcus-Bagley D. 1992. The immune response to hepatitis B vaccine in humans: Inheritance patterns in families. J Exp Med 175: 495-502. – reference: Ascherio A, Zhnag SM, Herbab MA, Olek MJ, Coplan PM, Brodovicz K, walker AM. 2001. Hepatitis B vaccination and the risk of multiple sclerosis. New Eng J Med 344: 327-332. – reference: Confavreux C, Suissa S, Saddier P, Bourdes V, Vukusic S. 2001. Vaccinations and the risk of relapse in multiple sclerosis. New Eng J Med 344: 319-326. – reference: Canada Communicable Disease Report. 1992. Adverse events following the administration of hepatitis B vaccines. Can Commun Dis Rep 18-7: 49-53. – reference: Jarrosson L, Kolopp-Sarda MN, Aguillar P, Bene MC, Faure GC, Kohler C. 2004. Most humoral non-responders to hepatitis B vaccines develop HBV-specific cellular immune responses. Vaccine 22: 3789-3796. – reference: Gonclaves L, Albarrar B, Salmen S, Borges L, Fields H, Montes H, Soyano A, Diaz Y, Berruta L. 2004. The non-response to hepatitis B vaccination is associated with impaired lymphocyte activation. Virology 326: 20-28. – reference: Carman WF, Zanetti AR, Karayiannis P, Waters J, Manzillo G, Tanzi E, Zuckerman AJ, Thomas HC. 1990. Vaccine-induced escape mutant of hepatitis B virus. Lancet 336: 325-329. – reference: Milich DR, McLachlan A, Chisari FV, Kent SB, Thornton GB. 1986. Immune response to the pre-S1 region of hepatitis B surface antigen: A pre-S1-specific T cell response can bypass non-responsiveness to the pre-S2 and S regions of HbsAg. J Immunol 137: 315-322. – reference: Autram B, Carcelain G, Combadiere B, Debre P. 2004. Therapeutic vaccines for chronic infections. Science 305: 205-208. – reference: Oon C-J, Lim G-K, Zaho Y, Goh K-T, Tan K-L, Yo S-L, Hopes E, Harrison TJ, Zuckerman AJ. 1995. Molecular epidemiology of hepatitis B virus vaccine variants in Singapore. Vaccine 13: 699-702. – reference: Canada Medical Association. 1993. Report of the working group on the possible relationship between hepatitis B vaccination and the chronic fatigue syndrome. Can Med Assoc J 149: 314-316. – reference: Hsu HY, Chang MH, Liaw SH, Ni YH, Chen HL. 1999. Changes of hepatitis B surface antigen variants in carrier children before and after universal vaccination in Taiwan. Hepatology 30: 1312-1317. – reference: Jefferson T. 1998. Vaccination and its adverse effects: Real or perceived. 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Snippet | Hepatitis B vaccines are highly effective and safe and have been incorporated into national immunization programs in over 150 countries. The major humoral... |
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SubjectTerms | Age Factors Alleles Biological and medical sciences DNA vaccines Fundamental and applied biological sciences. Psychology HBV mutants Hepatitis B - immunology Hepatitis B - prevention & control Hepatitis B Antibodies - blood Hepatitis B Surface Antigens hepatitis B vaccines Hepatitis B Vaccines - administration & dosage Hepatitis B Vaccines - genetics Hepatitis B Vaccines - immunology Hepatitis B Vaccines - therapeutic use Hepatitis B, Chronic - therapy HLA-DR Antigens - genetics Human viral diseases Humans immune response immunotherapy Infectious diseases Injections Medical sciences Microbiology Miscellaneous Mutation Safety Sex Factors T-Lymphocytes, Helper-Inducer - immunology Vaccination Vaccines, DNA Viral diseases Viral hepatitis Virology |
Title | Protective efficacy, immunotherapeutic potential, and safety of hepatitis B vaccines |
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