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158 HIV Envelope Peptide Cocktail Vaccine Protects against Chronic Infection and AIDS in the SHIV-Rhesus Model
P. N. Nehete*1, S. Chitta1, M. M. Hossain1, L. Hill1, R. B. Arlinghaus2, and K. J. Sastry1
Univ. of Texas M. D. Anderson Cancer Ctr., 1Bastrop, USA and 2Houston, USA
Background: We are pursuing a novel HIV vaccine concept based on the hypothesis that selective priming of cell-mediated immunity is important for preventing chronic infection and AIDS. Further, the vaccine should be multivalent consisting of peptide sequences from highly conserved regions of the virus that are broadly cross-reactive in the context of several MHC alleles. Based on our prior studies in mouse, monkey, chimpanzee, and human experimental systems, we have assembled a cocktail of 6 highly conserved HIV-1 envelope peptides as a prototype vaccine for testing in the SHIV-rhesus model.
Methods: Three monkeys were vaccinated with the peptide cocktail in Freund's adjuvant followed by autologous peptide-pulsed dendritic cells (DC). Two control monkeys received Freund's adjuvant and unpulsed DC. At 29 weeks post-immunization, the monkeys were challenged with SHIVKU-2 by the intravenous route.
Results: The vaccine elicited significant Th and CTL responses, but no neutralizing antibodies. Upon challenge with the pathogenic SHIVKU-2, antiviral CTL responses were boosted and virus-infected cells were cleared within 14 weeks in all 3 vaccinated animals. Antigen-specific IFN-gamma-producing cells were maintained beyond 42 weeks post-challenge. In contrast, both the control monkeys exhibited chronic infection indicated by significant levels of infected cells and plasma viremia beyond 38 weeks. In 1 control monkey, the CD4+ cells dropped to undetectable levels by week 39 post-challenge coinciding with high plasma viremia and AIDS. In a second study, separate groups of 7 and 6 monkeys each were vaccinated with the peptide cocktail in Freund's adjuvant and autologous DC, respectively. All the vaccinated monkeys exhibited strong CMI responses, and at 6 weeks post-challenge with SHIVKU-2 experienced 2(4 log reduction in virus-infected cells and a significant decrease in viral set point (p < 0.00005).
Conclusions: These results strongly support the multivalent peptide-based vaccine strategy to induce cellular immune responses for protection against chronic HIV infection and AIDS in humans.
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