IN-VIVO INDUCTION OF SPECIFIC CYTOTOXIC T-LYMPHOCYTES IN MICE AND RHESUS MACAQUES IMMUNIZED WITH DNA VECTOR ENCODING AN HIV EPITOPE FUSED WITH HEPATITIS-B SURFACE-ANTIGEN

DNA immunization offers a novel means to induce humoral and cellular i mmunity in inbred or in outbred animals. Here we have tested the effic iency of genetic immunization with hepatitis B virus (HBV) envelope-ba sed vectors. In naive primates, injection of a plasmid DNA encoding HB V envelope proteins induced an HBV-specific cytotoxic response and app earance of potentially protective anti-Has antibodies. Moreover, intra muscular and intradermal injections of a DNA expression vector encodin g an epitope of the human immunodeficiency virus envelope fused to the surface protein of the hepatitis B virus (HBsAg) induced strong humor al and cytotoxic responses to antigenic determinants of both viruses i n mice and nonhuman primates alike. In addition, in protein-primed Rhe sus monkeys B-cell memory was successfully boosted by DNA injection of hybrid vectors and animals subsequently developed a multispecific cel lular response. This suggests that DNA-based immunization could be use d to boost efficiently and broaden the immune response in individuals immunized with conventional vaccines, regardless of their genetic vari ability. These results also indicate that it might be possible to rati onally design HBsAg-based expression vectors to induce multispecific i mmune responses for vaccination against hepatitis B and other pathogen s. (C) 1998 Academic Press.