New Advances in Hepatitis B Vaccination for Adults
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Purpose of Review
The mainstay of elimination of hepatitis B virus is through primary prevention by vaccination recommended by the World Health Organization. This review seeks to update readers on the performance of the current second-generation vaccine and the challenges including primary and secondary vaccine failure, as well as compliance and coverage.
Primary vaccine failure in children may be overcome by HBIG and antiviral therapy in high-risk pregnancies, while in adults, a number of strategies to address this include intradermal delivery, double-dose vaccination, improved adjuvants, and a third-generation vaccine with pre-S1 and pre-S2 proteins. However, there is still no accepted standard therapy for primary vaccine failure. Secondary vaccine failure is less problematic with 3.9% of vaccines developing anti-HBc antibody, but only one reported case of chronicity has developed after vaccination.
The current second-generation prophylactic hepatitis B vaccines have performed extremely well, but there remain some challenges with regard to vaccine failure. A number of different strategies have been used to overcome this. Overall vaccine failure constitutes a relatively small proportion of vaccinees.
KeywordsHepatitis B vaccine Primary vaccine failure Secondary vaccine failure Vaccine non-compliance Pre-S1 Pre-S2 Adjuvants
Compliance with Ethical Standards
Conflict of Interest
Seng-Gee Lim reports grants, personal fees, and non-financial support from Gilead Sciences; personal fees from Abbvie; grants and personal fees from Abbott Diagnostics; grants and personal fees from Merck; grants and personal fees from Roche; and personal fees from Springbank outside the submitted work. Qingyao Daniel Huang declares no potential conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 1.Hepatitis B [Internet]. World Health Organization. [cited 2018 Jul 12]. Available from: http://www.who.int/news-room/fact-sheets/detail/hepatitis-b
- 10.Stephenne J. Development and production aspects of a recombinant yeast-derived hepatitis B vaccine. Vaccine 1990;8 Suppl:S69–73; discussion S79–80.Google Scholar
- 11.• Van Den Ende C, Marano C, Van Ahee A, Bunge EM, De Moerlooze L. The immunogenicity and safety of GSK’s recombinant hepatitis B vaccine in adults: a systematic review of 30 years of experience. Expert Rev Vaccines. 2017;16(8):811–32 A systematic review of Engerix B showing seroprotection rates of more than 90% in adults with an acceptable safety profile. CrossRefGoogle Scholar
- 12.• Schillie S. Prevention of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67. Available from: https://www.cdc.gov/mmwr/volumes/67/rr/rr6701a1.htm. The most up-to-date recommendations from the CDC regarding hepatitis B vaccination.
- 15.WHO | Global hepatitis report 2017. WHO. [cited 2018 Jul 12]. Available from: http://www.who.int/hepatitis/publications/global-hepatitis-report2017/en/
- 16.• Immunization coverage [Internet]. World Health Organization. [cited 2018 Jul 21]. Available from: http://www.who.int/news-room/fact-sheets/detail/immunization-coverage. World Health Organization data describing global coverage of newborns with the Hepatitis B vaccine.
- 17.• Auta A, Adewuyi EO, Kureh GT, Onoviran N, Adeloye D. Hepatitis B vaccination coverage among health-care workers in Africa: a systematic review and meta-analysis. Vaccine. 2018. Review showing suboptimal hepatitis B vaccine coverage among health care workers in Africa and describes reasons for poor compliance. Google Scholar
- 21.Omotowo IB, Meka IA, Ijoma UN, Okoli VE, Obienu O, Nwagha T, et al. Uptake of hepatitis B vaccination and its determinants among health care workers in a tertiary health facility in Enugu, South-East, Nigeria. BMC Infect Dis [Internet]. 2018 [cited 2018 Jul 24];18. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6027786/
- 24.WHO | Hepatitis B vaccination timing: results from demographic health surveys in 47 countries [Internet]. [cited 2018 Jul 23]. Available from: http://www.who.int.libproxy1.nus.edu.sg/bulletin/volumes/95/3/BLT-16-178822-table-T3.html
- 25.Wallace AS, Sobel H, Ryman TK, Mantaring JB, Silvestre M, Thorley M, et al. Timing of hepatitis B vaccination and impact of non-simultaneous vaccination with DTP vaccine following introduction of a hepatitis B birth dose in the Philippines. J Public Health Policy. 2012;33(3):368–81.CrossRefGoogle Scholar
- 26.• Whitford K, Liu B, Micallef J, Yin JK, Macartney K, Van Damme P, et al. Long-term impact of infant immunization on hepatitis B prevalence: a systematic review and meta-analysis. Bull World Health Organ. 2018;96(7):484–97 A systematic review and meta-analysis of the long-term impact of newborn vaccination on hepatitis B prevalence. This study also provides definitions for primary and secondary vaccine failure. CrossRefGoogle Scholar
- 30.•• Tai C-S, Wu J-F, Chen H-L, Ni Y-H, Hsu H-Y, Chang M-H. The impact of hepatitis B vaccine failure on long-term natural course of chronic hepatitis B virus infection in hepatitis B e antigen-seropositive children. J Infect Dis. 2017;216(6):662–9 A large cohort study from Taiwan that reports long-term consequences of vaccine failure. CrossRefGoogle Scholar
- 49.• Werner JM, Abdalla A, Gara N, Ghany MG, Rehermann B. The hepatitis B vaccine protects re-exposed healthcare workers, but does not provide sterilizing immunity. Gastroenterology. 2013;145(5). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3884684/. Describes how HBsAg vaccine protects against chronic infection but is not sterilizing, as evidenced by HBcore- and polymerase-specific CD8+ T cells in vaccinated personnel.):1026–34.CrossRefGoogle Scholar
- 51.• O’Halloran JA, De Gascun CF, Dunford L, Carr MJ, Connell J, Howard R, et al. Hepatitis B virus vaccine failure resulting in chronic hepatitis B infection. J Clin Virol. 2011;52(2):151–4 A case report of secondary vaccine failure in an immune competent adult resulting in the development of chronic hepatitis B. Escape mutants were not detected. CrossRefGoogle Scholar
- 57.Borges O, Tavares J, de Sousa A, Borchard G, Junginger HE, Cordeiro-da-Silva A. Evaluation of the immune response following a short oral vaccination schedule with hepatitis B antigen encapsulated into alginate-coated chitosan nanoparticles. Eur J Pharm Sci. 2007;32(4–5):278–90.CrossRefGoogle Scholar
- 62.• Guidelines, recommendations and resources | Dialysis Safety | CDC [Internet]. 2017 [cited 2018 Aug 21]. Available from: http://www.cdc.gov/dialysis/guidelines/index.html. Guidelines from the CDC recommending a higher dose of hepatitis B vaccine for patients on hemodialysis.
- 64.Chaiklang K, Wipasa J, Chaiwarith R, Praparattanapan J, Supparatpinyo K. Comparison of immunogenicity and safety of four doses and four double doses vs. standard doses of hepatitis B vaccination in HIV-infected adults: a randomized, controlled trial. PLoS One. 2013;8(11):e80409.CrossRefGoogle Scholar
- 68.•• A two-dose hepatitis B vaccine for adults (Heplisav-B). JAMA 2018;319(8):822–3. A review article describing a two-dose hepatitis B vaccine. Google Scholar
- 69.Halperin SA, Dobson S, McNeil S, Langley JM, Smith B, McCall-Sani R, et al. Comparison of the safety and immunogenicity of hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide and a licensed hepatitis B vaccine in healthy young adults. Vaccine. 2006;24(1):20–6.CrossRefGoogle Scholar
- 70.Halperin SA, Ward B, Cooper C, Predy G, Diaz-Mitoma F, Dionne M, et al. Comparison of safety and immunogenicity of two doses of investigational hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide and three doses of a licensed hepatitis B vaccine in healthy adults 18-55 years of age. Vaccine. 2012;30(15):2556–63.CrossRefGoogle Scholar
- 71.Heyward WL, Kyle M, Blumenau J, Davis M, Reisinger K, Kabongo ML, et al. Immunogenicity and safety of an investigational hepatitis B vaccine with a toll-like receptor 9 agonist adjuvant (HBsAg-1018) compared to a licensed hepatitis B vaccine in healthy adults 40–70 years of age. Vaccine. 2013;31(46):5300–5.CrossRefGoogle Scholar
- 72.• Jackson S, Lentino J, Kopp J, Murray L, Ellison W, Rhee M, et al. Immunogenicity of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant compared with a licensed hepatitis B vaccine in adults. Vaccine. 2018;36(5):668–74 A large phase III randomized controlled trial comparing a novel two-dose hepatitis B vaccine against a second generation vaccine. CrossRefGoogle Scholar
- 73.•• Schillie S, Harris A, Link-Gelles R, Romero J, Ward J, Nelson N. Recommendations of the Advisory Committee on Immunization Practices for use of a hepatitis B vaccine with a novel adjuvant. MMWR Morb Mortal Wkly Rep. 2018;67(15):455–8 The CDC recommendations regarding a two-dose hepatitis B vaccine. CrossRefGoogle Scholar
- 78.• Elhanan E, Boaz M, Schwartz I, Schwartz D, Chernin G, Soetendorp H, et al. A randomized, controlled clinical trial to evaluate the immunogenicity of a PreS/S hepatitis B vaccine Sci-B-Vac™, as compared to Engerix B®, among vaccine naïve and vaccine non-responder dialysis patients. Clin Exp Nephrol. 2018;22(1):151–8 A randomized controlled trial comparing immunogenicity in the third-generation vaccine against the second generation vaccine in dialysis patients. CrossRefGoogle Scholar