COMPARISON OF ADJUVANT FORMULATIONS FOR CYTOTOXIC T-CELL INDUCTION USING SYNTHETIC PEPTIDES

We have investigated the capacity of synthetic peptides delivered in d ifferent adjuvant formulations to induce cytotoxic T lymphocyte (CTL) responses to a class I H-2K(d)-restricted Plasmodium berghei circumspo rozoite epitope, CS 252-260. Using three immunogen formulations: soybe an emulsion, Montanide ISA720; and lipopeptide (P3-CS), we first evalu ated the effects of immunization routes on CTL induction. No CTL respo nse tvas induced in mice immunized s. c. or i.p. with CS peptide formu lated in soybean emulsion. In contrast, immunization with lipopeptide P3-CS either s.c. or i.p. effectively primed for CTL. Interestingly CS peptide emulsified in Montanide ISA720 induced a CTL response only wh en delivered s.c. and Mot i.p., indicating the critical influence of i mmunization routes on CTL induction, We then compared the effectivenes s of eight adjuvant formulations to induce CTL response following a si ngle s.c. immunization. Notably, lipopeptide P3-CS and CS peptide admi xed with P3 or POE lipid molecules stimulated a vigorous CTL response. However, only mice immunized with P3-CS and CS peptide admixed with P 3 molecule generated long-lilted CTL which persisted in vivo for 5 mon ths. Thus, based on a simultaneous comparison of the different adjuvan t formulations, we demonstrated that the conjugated and unconjugated P 3 lipopeptides were the most effective immunogens for eliciting primar y and memory CTL in mice. Copyright (C) 1996 Elsevier Science Ltd.