Peptide immunization restimulates the memory CD4 T cell response but fails to induce cytotoxic T lymphocytes in cynomolgus monkeys

Abstract

A potential strategy to induce peptide specific CTL in vivo was investigated. A synthetic vaccine consisting of an SIV-derived, HLA-A2. 1-binding CTL epitope and a tetanus toxin-derived T helper epitope was evaluated for its capacity to induce peptide-specific CTL in monkeys. Thirteen animals were immunized and boosted twice with 150 microg of CTL plus 250 microg of the T helper peptide (p30). Peripheral blood mononuclear cells (PBMC) were regularly analysed for cytotoxic and proliferative responses before, between, and after the immunizations, and the serum was tested for anti-peptide antibodies. No unequivocal induction of SIV peptide-specific CTL in any of the monkeys was observed. However, a wide pattern of mild and transient side reactions were observed, ranging from local redness at the injection site to generalized exanthema, myalgias, arthralgias, and fever. The side-effects were related to the T helper epitope, as they were similar to the side-effects experienced after tetanus immunization, correlated to the magnitude of the p30-specific in vitro proliferative response, and occurred only if p30 was co-injected. No antibody against the SIV-derived peptides nor against p30 was detectable in the serum after repeated immunizations. The data suggest that the CTL peptide, at the concentration used in this study, failed to induce a cytotoxic immune response in vivo, although the T helper peptide seems to be capable of restimulating the specific memory T cells.