EPITOPE POLARITY AND ADJUVANTS INFLUENCE THE FINE SPECIFICITY OF THE HUMORAL RESPONSE AGAINST SEMLIKI-FOREST-VIRUS SPECIFIC PEPTIDE VACCINES

humoral response to synthetic peptide vaccines against Semliki Forest virus (SFV) in H-2(d) BALB/c mice was investigated with the enzyme lin ked immunosorbent assay and the pepscan technique. The peptide vaccine s consisted of amino acid sequences 240-255 (B) and 137-151 (T) of the E2 membrane protein of SFV colinearly synthesized in either orientati on T-B or B-T Sequence B contains an epitope inducing humoral immunity to lethal SFV infection and sequence T contains a H-2(d) restricted T -helper cell epitope. with sera from mice immunized subcutaneously wit h peptide T-B, and Quil A as adjuvant, two immunodominant B-cell epito pes were identified FVPRAD, at position 240-246 and PHYGKEI, at positi on 145-151. However; with peptide B-T and Quil A as adjuvant for immun ization the epitope PHYGKEI was clearly immunodominant, but antibodies elicited against this epitope were not reactive with SFV-infected L c ells in contrast to the antibodies elicited by epitope FVPRAD. An addi tional epitope EPARKGKVH, at position 247-255, was identified with ser a from mice immunized subcutaneously with either peptide T-B or B-T an d Montanide ISA 740 as an adjuvant. Monoclonal antibodies selected for reactivity with SFV-infected L cells did bind also to epitope FVPRAD. Interestingly, this epitope could induce antibodies cross-reactive wi th a synthetic peptide derived from macrophage migration inhibitory fa ctor that shares amino acid residues VPRA at position 9-12 with the pr otective B-cell epitope FVPRAD. The present study shows clearly that t he fine specifi city of the humoral response against peptide vaccines is differentially influenzed by bath adjuvant and epitope polarity whi ch may affect vaccine efficacy. Further; the study reminds us that pot entially autoimmune antibodies could be induced by vaccines. (C) 1998 Elsevier Science Ltd. All rights reserved.