CANDIDATE HIV TYPE-1 MULTIDETERMINANT CLUSTER PEPTIDE-P18MN VACCINE CONSTRUCTS ELICIT TYPE-1 HELPER T-CELLS, CYTOTOXIC T-CELLS, AND NEUTRALIZING ANTIBODY, ALL USING THE SAME ADJUVANT IMMUNIZATION

Cytotoxic T lymphocytes and Th1 cells have been suggested to play a cr itical role in the control of HIV infection, It is therefore considere d that a vaccine that induces a strong Th1 response and CTL response w ould be more efficacious than one that does not in providing protectio n against infection and progression toward AIDS. In this study we show that immunization with vaccine constructs consisting of multidetermin ant cluster peptides containing Th epitopes from the HIV-1IIIB envelop e colinearly synthesized to peptide 18MN, is capable of inducing a Th1 response in mice and, dependent on this help, both cytotoxic T cell r esponses and neutralizing antibody toward the homologous strain of HIV , Moreover, the cytotoxic T cell response elicited by immunization wit h a mixture of cluster peptide-P18MN vaccine constructs was at least a s cross-reactive against known viral variant P18 target sequences as a CTL line produced by immunization with a vaccinia construct expressin g recombinant gp160 MN. Four adjuvants were compared to optimize both CTL and antibody responses. A single adjuvant formulation of peptide i n ISA 51 could elicit all three: Th1 cells, CTLs, and neutralizing ant ibody. Thus, immunization directed toward the development of a cytotox ic T cell response does not preclude the development of neutralizing a ntibody and vice versa, i.e., the responses are not mutually exclusive . The immunization protocol described here should be directly applicab le for study in clinical trials aimed at HIV-1 immunotherapy or prophy laxis.