IMMUNIZATION OF HUMAN HIV-SERONEGATIVE VOLUNTEERS WITH RECOMBINANT P17 P24-TY VIRUS-LIKE PARTICLES ELICITS HIV-1 P24-SPECIFIC CELLULAR AND HUMORAL IMMUNE-RESPONSES/

Objective: To evaluate the immune response to HIV-1 p24 generated in v ivo by p17/p24:Ty virus-like particles (p17/p24:Ty-VLP) by examining t he lymphoproliferative and antibody (Ab) responses to HIV-1 p24, as we ll as Gag-specific cytotoxic T lymphocytes (CTL), in HIV-seronegative volunteers immunized with hybrid p17/p24:Ty-VLP. Design and methods: S ixteen HIV-seronegative volunteers were immunized with pl 7/p24:Ty-VLP at two dose levels (100 or 500 mug) and monitored for the following 4 8 weeks for production of anti-p24 and anti-p17 Ab, in vitro lymphopro liferative responses to HIV-1 p24 and p17, and in vitro CTL responses to HIV-1 Gag. Results: Twelve out of the 16 volunteers had significant p24-specific proliferative responses, with volunteers on the higher d ose schedule exhibiting earlier proliferative responses than those on the lower dose schedule. Proliferative responses in both volunteer gro ups were similar in overall magnitude but appeared at different times during the immunization schedule. Anti-p24 Ab were detected in six out of the nine individuals in the lower dose group and in five out of th e seven in the higher dose group. There was a good correlation between the presence of p24-specific Ab and the detection of lymphoproliferat ive responses to the p24 protein in peripheral blood mononuclear cells isolated from the same individuals. Anti-p17 Ab were detected in five volunteers. No Gag-specific CTL responses were detected. Conclusion: We conclude that hybrid HIV-1 p17/p24:Ty-VLP are capable of inducing b oth cellular and humoral immunity to HIV-1 Cag p17 and p24 components and are worthy of further study as a potential HIV immunotherapeutic.