Peptide immunization restimulates the memory CD4 T cell response but fails to induce cytotoxic T lymphocytes in cynomolgus monkeys.
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.
Mavoungou
E
E
Unit of Immunology, International Center for Medical Research, Franceville, (CIRMF), Gabon. emavoung@cirmfrv.fr
Toure
F S
FS
Yaba
P
P
Délicat
A
A
Poaty-Mavoungou
V
V
D000818:Animals; D015704:CD4 Antigens / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology; D007114:Immunization / Q000662:veterinary*; D008213:Lymphocyte Activation; D008252:Macaca fascicularis / Q000276:immunology; D008297:Male; D010446:Peptide Fragments; D018449:SAIDS Vaccines / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D013744:Tetanus Toxin / Q000276:immunology
D015704:CD4 Antigens; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D018449:SAIDS Vaccines; D013744:Tetanus Toxin