Improved immunogenicity in mice of a mammalian cell-derived recombinant hepatitis B vaccine containing pre-S1 and pre-S2 antigens as compared with conventional yeast-derived vaccines

Vaccine. 1994 Nov;12(15):1453-9. doi: 10.1016/0264-410x(94)90155-4.


The widely used hepatitis B virus (HBV) vaccines consist of the small hepatitis B surface (SHBs) protein produced in transfected yeast cells. The frequency of non-responders, especially among immunocompromised patients, has increased the demand for a more immunogenic vaccine. We evaluated the immunogenicity of recombinant HBs 20 nm particles secreted by transfected Chinese hamster ovary (CHO) cells, Bio-Hep-B (BioTechnology General Ltd, Israel), and compared it with yeast-derived vaccines. The CHO-derived vaccine contains the small hepatitis B surface antigen (SHBs protein) as the major component, as well as the middle HBs (MHBs, pre-S2) and the large HBs (LHBs, pre-S1) antigens. Nine groups of ten female Balb/c mice, 4-6 weeks old, were injected once intraperitoneally (i.p.) with 0.09, 0.27 or 0.81 micrograms of each of three vaccines: Bio-Hep-B or two conventional yeast-derived recombinant vaccines, Engerix-B (SmithKline Beecham, Belgium) and H-B-Vax II (Merck, Sharp & Dohme, USA) containing only non-glycosylated SHBs antigen. After 30 days, 40% of the mice injected with 0.09 microgram Bio-Hep-B had seroconverted, but none of the mice receiving the same dose of the other vaccines. The immunogenic dose in 50% of the mice at day 14 after injection was 0.13 microgram for Bio-Hep-B, but over 0.81 microgram for the other two vaccines. Mice of the strain B10/M (which are unresponsive to SHBs and MHBs antigens at the T-cell level) developed 100-fold higher anti-HBs titres after immunization with 1 microgram of Bio-Hep-B i.p., as compared with mice receiving the same amount of yeast-derived HBsAg vaccines.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cricetinae
  • Epitopes / immunology
  • Female
  • Hepatitis B Surface Antigens / immunology*
  • Hepatitis B Vaccines / genetics
  • Hepatitis B Vaccines / immunology*
  • Mice
  • Mice, Inbred Strains
  • Protein Precursors / immunology*
  • Saccharomyces cerevisiae / genetics
  • Species Specificity
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology*
  • Viral Envelope Proteins / immunology*


  • Epitopes
  • Hepatitis B Surface Antigens
  • Hepatitis B Vaccines
  • Protein Precursors
  • Vaccines, Synthetic
  • Viral Envelope Proteins
  • presurface protein 1, hepatitis B surface antigen
  • presurface protein 2, hepatitis B surface antigen