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. str ategy to induce peptide-specific CTL in vivo. In this study, a synthet ic vaccine consisting of an HIV-derived, HLA-A2.1-binding CTL epitope and a tetanus toxin-derived T helper epitope was evaluated for its cap acity to induce peptide-specific CTL in humans. Thirteen volunteers we re immunized and boosted twice with 100 mu g of the CTL epitope plus 3 00 mu g of the T helper peptide (p30). Peripheral blood mononuclear ce lls (PBMC) were regularly analysed for cytotoxic and proliferative res ponses before, between and after the immunizations, and the serum was tested for anti-peptide antibodies. No unequivocal induction of HIV pe ptide-specific CTL in any of the volunteers was observed. However, a w ide pattern of mild and transient side reactions was observed, ranging from local redness at the injection site to generalized exanthema, my algias, arthralgias and fever. The side-effects were related to the T helper epitope, as they were similar to tile side-effects experienced after tetanus immunization, correlated to the magnitude of the p30-spe cific 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 dat a suggest that the CTL peptide: at the concentration used in this stud y, failed to induct a cytotoxic immune response in vivo, although the T helper peptide seems to be capable of restimulating the specific mem ory T cells.