IMPROVED IMMUNOGENICITY IN MICE OF A MAMMALIAN CELL-DERIVED RECOMBINANT HEPATITIS-B VACCINE CONTAINING PRE-S-1 AND PRE-S-2 ANTIGENS AS COMPARED WITH CONVENTIONAL YEAST-DERIVED VACCINES

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 secret ed by transfected Chinese hamster ovary (CHO) cells, Bio-Hep-B (BioTec hnology General Ltd, Israel), and compared it with yeast-derived vacci nes. The CHO-derived vaccine contains the small hepatitis B surface an tigen (SHBs protein) as the major component, as well as the middle HBs (MHBs, pre-S-2) and the large HBs (LHBs, pre-S-1) antigens. Nine grou ps of ten female Balb/c mice, 4-6 weeks old, were injected ones intrap eritoneally (i.p.) with 0.09, 0.27 or 0.81 mu g of each of three vacci nes. Bio-Hep-B or two conventional yeast-derived recombinant vaccines, Engerix-B (SmithKline Beecham, Belgium) and H-B-Vax II (Merck, Sharp and Dohme, USA) containing only non-glycosylated SHBs antigen. After 3 0 days, 40% of the mice injected with 0.09 mu g Bio-Hep-B had seroconv erted, but none of the mice receiving the same dose of the other vacci nes. The immunogenic dose in 50% of the mice at day 14 after injection was 0.13 mu g for Bio-Hep-B, but over 0.81 mu g for the other two vac cines. Mice of the strain B10/M (which are unresponsive to SHBs and MH Bs antigens at the T-cell level) developed 100-fold higher anti-HBs ti tres after immunization with 1 mu g of Bio-Hep-B i.p., as compared wit h mice receiving the same amount of yeast-derived HBsAg vaccines. Anti bodies to sequential LHBs and MHBs antigens were detected in mice or r abbits immunized with Bio-Hep-B, but not in mice injected with the oth er SHBs vaccines. These results indicate that the new recombinant vacc ine, produced from CHO cells transfected with HBV DNA encoding for all three HBs antigens, elicits an augmented anti-HBs response in mice as compared with mice receiving the currently used yeast-derived vaccine s. It remains to be seen whether the enhanced seroconversion rate and anti-HBs titres induced by this vaccine in mice will be of benefit in humans and will increase efficacy and prolong the duration of protecti on against HBV.