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Prophylactic vaccination against hepatitis B: achievements, challenges and perspectives

Abstract

Large-scale vaccination against hepatitis B virus (HBV) infection started in 1984 with first-generation vaccines made from plasma of chronic carriers containing HBV surface antigen (HBsAg). Thereafter, it was replaced in most countries by second-generation vaccines manufactured in yeast cells transformed with gene S encoding HBsAg. Both generations of vaccines have been applied for universal neonate and early childhood vaccination worldwide and have led to a 70–90 % decrease in chronic HBV carrier rates. However, 10–30 % of newborns from HBsAg/HBeAg-positive mothers cannot be protected by passive/active vaccination alone and become chronic HBV carriers themselves. Asymptomatic occult HBV infections are frequent even in those who have protective levels of anti-HBs. Suboptimal protection may be due to heterologous HBsAg subtypes that are present in 99 % of HBV carriers worldwide. Second-generation vaccines contain partially misfolded HBsAg and lack preS1 antigen that carries the major HBV attachment site and neutralizing epitopes. Third-generation vaccines produced in mammalian cells contain correctly folded HBsAg and neutralizing epitopes of the preS antigens, induce more rapid protection, overcome nonresponse to second-generation vaccines and, most importantly, may provide better protection for newborns of HBV-positive mothers. PreS/S vaccines expressed in mammalian cells are more expensive to manufacture, but introduction of more potent HBV vaccines should be considered in regions with a high rate of vertical transmission pending assessment of health economics and healthcare priorities. With optimal vaccines and vaccination coverage, eradication of HBV would be possible.

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Acknowledgments

The author thanks Dieter Glebe, Michael Roggendorf and Daniel Shouval for critical reading and fruitful collaboration over decades.

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Correspondence to Wolfram H. Gerlich.

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This article is part of the special issue “Therapeutic vaccination in chronic hepatitis B—approaches, problems, and new perspectives”.

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Gerlich, W.H. Prophylactic vaccination against hepatitis B: achievements, challenges and perspectives. Med Microbiol Immunol 204, 39–55 (2015). https://doi.org/10.1007/s00430-014-0373-y

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Keywords

  • Hepatitis B virus
  • HBsAg
  • Vaccine
  • PreS
  • Mother-to-child transmission
  • Escape mutant