A VACCINE-ELICITED, SINGLE VIRAL EPITOPE-SPECIFIC CYTOTOXIC T-LYMPHOCYTE RESPONSE DOES NOT PROTECT AGAINST INTRAVENOUS, CELL-FREE SIMIAN IMMUNODEFICIENCY VIRUS CHALLENGE

Protection against simian immunodeficiency virus (SIV) challenge was assessed in rhesus monkeys with a vaccine-elicited, single SIV epitope-specific cytotoxic T-lymphocyte (CTL) response in the absence of SIV-specific antibody. Strategies were first explored for eliciting an optimal SIV Gag epitope-specific CTL response, These studies were performed in rhesus monkeys expressing the major histocompatibility complex (MHC) class I gene Mamu-A*01, a haplotype associated with a predominant SIV CTL epitope mapped to residues 182 to 190 of the Gag protein (p11C). We demonstrated that a combined modality immunization strategy using a recombinant Mycobacterium bovis BCG-SIV Gag construct for priming, and peptide formulated in liposome for boosting, elicited a greater p11C-specific CTL response than did a single immunization with peptide-liposome alone. Vaccinated and control monkeys were then challenged with cell-free SIVmine by an intravenous route of inoculation. Despite a vigorous p11C-specific CTL response at the time of virus inoculation, all monkeys became infected with SIV. gag gene sequencing of the virus isolated from these monkeys demonstrated that the established viruses had no mutations in the p11C-coding region, Thus, the preexisting CTL response did not select for a viral variant that might escape T-cell immune recognition, These studies demonstrate that a potent SIV-specific CTL response can be elicited by combining live vector and peptide vaccine modalities, However, a single SIV Gag epitope-specific CTL response in the absence of SIV-specific antibody did not provide protection against a cell-free, intravenous SIV challenge.