Hepatitis B vaccine containing surface antigen and selected preS1 and preS2 sequences 2. Immunogenicity in poor responders to hepatitis B vaccines

The immunogenicity of a yeast-derived recombinant hepatitis B virus (HBV) vaccine containing surface antigen (S) and selected preS1 and preS2 sequences (S-L ∗) was compared with that of a vaccine containing S alone (Engerix™-B) in 32 healthy adults with a previous history of poor response (anti-HBs < 10 mIU ml −1) after at least three consecutive monthly doses of hepatitis B vaccines. The poor responders were randomized to receive three additional 20-μg doses of either S-L ∗ or Engerix™-B in a double-blind fashion according to a 0-, 1-, 2-month schedule. In vivo humoral and in vitro lymphoproliferative responses to the S and preS regions were monitored. Although the addition of the selected preS sequences to S did not enhance the in vivo humoral anti-HBs response, the administration of the three additional vaccine doses, irrespective of their preS content, induced seroprotective anti-HBs levels 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.