Peptide based cytotoxic T-cell vaccines; delivery of multiple epitopes, help, memory and problems

Synthetic CD8+ cytotoxic T-lymphocyte (CTL) peptide epitope based vaccines are being developed against a number of human diseases. Here we describe ex tensive preclinical testing of peptide epitope vaccines formulated with a p rotein as a source of CD4 help and Montanide ISA 720, an adjuvant currently in human clinical trials. Such water-in-oil formulations could effectively co-deliver several peptide epitopes and simultaneously induce multiple ind ependent CTL responses. The efficiency of CTL induction by some peptides wa s, however, dependent on the aqueous buffer conditions, with poor performan ce correlating with non-covalent peptide oligomerisation, Any of a number o f proteins currently used in human vaccines could supply CD4 help and no di fference in CTL induction was obtained if the CD4 response was amnestic or a primary. Peptide immunisation was found to induce long term CTL memory an d the recall of protective responses did not depend on an amnestic CD4 resp onse. Slow pyroglutamic acid formation and rapid oxidation of methionine re sidues was observed in water-in-oil formulations, however, the latter had n o effect on CTL induction. These data highlight the need to monitor for pot ential deleterious chemical events and interpeptide interactions, but illus trate that peptide based vaccination can effectively deliver multiple epito pes, in conjunction with any protein, and induce protective memory. (C) 199 9 Elsevier Science Ltd. All rights reserved.