MODIFICATION OF DELIVERY SYSTEM ENHANCES MHC NONRESTRICTED IMMUNOGENICITY OF V3 LOOP REGION OF HIV-1 GP120

A successful peptide vaccine for AIDS is desired to elicit T-helper an d cytotoxic T lymphocyte responses besides neutralizing antibodies. Th e V3 loop peptide of HIV-1 has been shown to contain the principal neu tralizing domain, one of the most immunodominant regions, having both B-cell and T-cell determinants. In this study, the tip of the V3 loop region was mutated from GPGR to GPGQ based on the sequence of Indian i solates (CKRKIHIGPGQAFYT). To further enhance the immunogenicity of th is epitope, two delivery systems of immune stimulating complexes (ISCO Ms) and liposomes were used to incorporate the peptide. Mice of differ ing haplotypes, H-2(b), H-2(d), H-2(k) and H-2(s). showed no MHC restr iction when immunized with these formulations. The IgG levels as asses sed by ELISA were found to be significantly higher (P<0.05 to P<0.001) for even five-fold lower doses of the peptide in ISCOMs and Liposomes as compared to the conventional alum-based preparation. The major sub type elicited was IgG2a/IgG2b, suggestive of a Th1-like response for a ll the formulations. Thus, it would appear that the same peptide incor porated in ISCOMs and liposomes selects a Th1 response and may therefo re be important not only for neutralization but also for virus clearan ce.