Peptide immunization in humans: a combined CD8 + /CD4 + T cell‐targeted vaccine restimulates the memory CD4 T cell response but fails to induce cytotoxic T lymphocytes (CTL)

Immunization with short antigenic peptides represents a potential strategy to induce peptide‐specific CTL in vivo . In this study, a synthetic vaccine consisting of an HIV‐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 humans. Thirteen volunteers were immunized and boosted twice with 100 μg of the CTL epitope plus 300 μg 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 HIV peptide‐specific CTL in any of the volunteers was observed. However, a wide pattern of mild and transient side reactions was 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 antibodies against the HIV‐derived peptides nor against p30 were 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.