HEPATITIS-B VACCINE CONTAINING SURFACE-ANTIGEN AND SELECTED PRES1 ANDPRES2 SEQUENCES .2. IMMUNOGENICITY IN POOR RESPONDERS TO HEPATITIS-B VACCINES

The immunogenicity of a yeast-derived recombinant hepatitis B virus (H BV) vaccine containing surface antigen (S) and selected preS1 and preS 2 sequences (S-L) was compared with that of a vaccine containing S al one (Engerix(TM)-B) in 32 healthy adults with a previous history of po or response (anti-HBs < 10 mIU ml(-1)) after at least three consecutiv e monthly doses of hepatitis B vaccines. The poor responders were rand omized to receive three additional 20-mu g doses of either S-L or Eng erix(TM)-B in a double-blind fashion according to a 0-, 1-, 2-month sc hedule. In vivo humoral and in vitro lymphoproliferative responses to the S and preS regions were monitored. Although the addition of the se lected preS sequences to S did not enhance the in vivo humoral anti-HB s response, the administration of the three additional vaccine doses, irrespective of their preS content, induced seroprotective anti-HBs le vels in most vaccinees (29/32, 91%). In vitro proliferative responses to HBV surface antigens were only observed in subjects displaying anti -HBs titers > 1000 mIU ml(-1) after the third additional vaccine dose. (C) 1997 Elsevier Science Ltd.