Display options
Share it on

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2022 Jan 11; doi: 10.1007/s00103-021-03484-w. Epub 2022 Jan 11.

[Hepatitis B vaccines-history, achievements, challenges, and perspectives].

Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz

[Article in German]
Wolfram H Gerlich

Affiliations

  1. Institut für Medizinische Virologie, Nationales Referenzzentrum für Hepatitis-B-Viren und Hepatitis-D-Viren, Justus-Liebig-Universität Gießen, Schubertstr. 81, 35392, Gießen, Deutschland. [email protected].

PMID: 35015108 PMCID: PMC8751463 DOI: 10.1007/s00103-021-03484-w

Abstract

The first experimental vaccinations against hepatitis B virus (HBV) were performed in 1970, even before the nature of the administered "Australia antigen" was known. Soon, it was realized that this antigen was the envelope protein (HBV surface antigen, HBsAg), and it was purified from HBV-containing human plasma. Later, it was produced in genetically engineered yeast cells. The excellent efficacy of the HBsAg vaccine was confirmed in numerous studies, particularly in newborns from HBV-infected mothers who almost always become chronic HBV carriers without vaccination. But the vaccine is also highly effective in older children and adults and has been applied worldwide since 1984, leading to a circa tenfold decrease of HBV infections in the vaccinated.Still, there are several challenges with hepatitis B vaccination. In newborns from mothers with very high virus load, the vaccine may fail. Recipients who are immunocompromised, older, smokers, or obese may not produce protective antibodies. Early studies suggested that the vaccine with HBsAg subtype adw2 also protected against infections by other subtypes, but recent observations show that the protection is weaker against heterologous subtypes. Occasionally, escape mutations may develop.Most current HB vaccines are based on the knowledge of 40 years ago and could be significantly improved. Inclusion of the currently neglected preS domains in the HBV envelope would add the most important protective T‑ and B‑cell epitopes to the vaccines. Expression of the HBsAg in mammalian cell cultures would enhance the folding of neutralizing HBsAg epitopes. Use of the regionally prevalent HBsAg subtypes would increase the protection. Optimal adjuvants and epitope carriers may enhance the immunogenicity to the level necessary for immune therapy of chronic hepatitis B.

© 2022. The Author(s).

Keywords: HBV; HBsAg; Neutralizing antibody; PreS1; Protective epitopes

References

  1. Dig Dis Sci. 2021 Jun;66(6):2101-2106 - PubMed
  2. Lancet Infect Dis. 2021 Sep;21(9):1271-1281 - PubMed
  3. J Biol Stand. 1980;8(1):59-68 - PubMed
  4. Am J Med Sci. 1975 Sep-Oct;270(2):395-9 - PubMed
  5. Adv Exp Med Biol. 1987;225:233-9 - PubMed
  6. Intervirology. 2014;57(3-4):141-50 - PubMed
  7. N Engl J Med. 1980 Oct 9;303(15):833-41 - PubMed
  8. J Infect Dis. 2009 Jul 1;200(1):33-8 - PubMed
  9. Med Microbiol Immunol. 2015 Feb;204(1):39-55 - PubMed
  10. Expert Opin Biol Ther. 2008 Feb;8(2):235-47 - PubMed
  11. Hepatol Res. 2003 Aug;26(4):287-292 - PubMed
  12. Viruses. 2020 Jan 21;12(2): - PubMed
  13. Med Microbiol Immunol. 2015 Feb;204(1):57-68 - PubMed
  14. Lancet. 1981 Aug 22;2(8243):388-93 - PubMed
  15. Am J Med Sci. 1972 Jan;263(1):27-33 - PubMed
  16. Lancet. 1981 Feb 7;1(8215):289-92 - PubMed
  17. Hum Vaccin Immunother. 2020;16(2):251-268 - PubMed
  18. EBioMedicine. 2020 Sep;59:102953 - PubMed
  19. Virus Genes. 2020 Oct;56(5):546-556 - PubMed
  20. J Natl Cancer Inst. 2009 Oct 7;101(19):1348-55 - PubMed
  21. J Med Virol. 2013 Apr;85(4):597-601 - PubMed
  22. JAMA. 1971 Jul 5;217(1):41-5 - PubMed
  23. JAMA. 1967 May 1;200(5):365-73 - PubMed
  24. J Hepatol. 2011 Jul;55(1):29-37 - PubMed
  25. Sci Rep. 2021 Apr 21;11(1):8676 - PubMed
  26. J Gastroenterol Hepatol. 2010 Jan;25(1):19-25 - PubMed
  27. Science. 1972 Dec 22;178(4067):1300-1 - PubMed
  28. J Med Virol. 1983;11(1):1-9 - PubMed
  29. Z Gastroenterol. 2021 Jul;59(7):691-776 - PubMed
  30. EBioMedicine. 2016 Sep;11:58-67 - PubMed
  31. N Engl J Med. 1982 Dec 9;307(24):1481-6 - PubMed
  32. JAMA. 1989 Jun 9;261(22):3278-81 - PubMed
  33. Vaccine. 2021 Jun 8;39(25):3346-3352 - PubMed
  34. J Virol. 1974 Aug;14(2):384-91 - PubMed
  35. Virus Genes. 2020 Apr;56(2):109-119 - PubMed
  36. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4549-53 - PubMed
  37. N Engl J Med. 2018 Mar 08;378(10):911-923 - PubMed
  38. Proc Natl Acad Sci U S A. 1977 Apr;74(4):1530-4 - PubMed
  39. Hepatology. 2013 Jan;57(1):37-45 - PubMed
  40. Br Med J (Clin Res Ed). 1983 Apr 23;286(6374):1305-8 - PubMed
  41. J Virol. 1984 Nov;52(2):396-402 - PubMed
  42. Vaccines (Basel). 2021 Apr 01;9(4): - PubMed
  43. Proc Soc Exp Biol Med. 1976 Apr;151(4):694-700 - PubMed
  44. Elife. 2017 Sep 26;6: - PubMed
  45. Dtsch Med Wochenschr. 1982 Jan 29;107(4):125-31 - PubMed
  46. Biologicals. 2017 Nov;50:3-19 - PubMed
  47. N Engl J Med. 2016 Jun 16;374(24):2324-34 - PubMed
  48. Am J Med Sci. 1975 Sep-Oct;270(2):401-4 - PubMed
  49. Lancet. 1976 Jun 26;1(7974):1367-70 - PubMed
  50. Hepatology. 2015 Mar;61(3):823-33 - PubMed
  51. J Exp Med. 2020 Oct 5;217(10): - PubMed
  52. Proc Natl Acad Sci U S A. 1979 May;76(5):2222-6 - PubMed
  53. N Engl J Med. 2011 Jan 20;364(3):236-47 - PubMed
  54. Virol J. 2013 Jul 20;10:239 - PubMed
  55. Clin Immunol. 2016 Aug;169:16-27 - PubMed
  56. Antiviral Res. 2016 Jul;131:109-23 - PubMed
  57. Hepatology. 2011 Feb;53(2):429-36 - PubMed
  58. Nature. 1979 May 3;279(5708):43-7 - PubMed
  59. Nature. 1982 Oct 21;299(5885):740-2 - PubMed
  60. Proc Natl Acad Sci U S A. 1968 Jul;60(3):814-21 - PubMed
  61. Nature. 1979 Aug 30;280(5725):815-9 - PubMed

Publication Types