Antibody responses to a synthetic peptide-based malaria vaccine candidate: influence of sequence variants of the peptide.

A synthetic peptide (Asn-Ala-Asn-Pro)3, representing a protective sequence from the sporozoite stage of Plasmodium falciparum, conjugated to tetanus toxoid has undergone clinical testing. Although some protection was obtained, anti-parasite responses were generally low. In attempting to improve the anti-parasite protein antibody response, we evaluated the efficacy of tetanus toxoid conjugates containing seven sequence variants of the peptide. Most of the conjugates tested in both mice and monkeys elicited anti-peptide antibodies with fine specificity differences, although there was a broad degree of cross-reactivity. In general, each conjugate tested evoked similarly high anti-sporozoite antibody responses in both species and, thus, based on antibody titer no evidence for a superior vaccine candidate was obtained. The biological activity of one antiserum actually increased the penetration of sporozoites into human liver cells. In contrast, antisera against the other conjugates inhibited sporozoite penetration, but to a similar degree. Based on these two criteria, none of the other conjugates would appear to be better vaccine candidates than the original conjugate. The lack of concordance between anti-peptide or anti-sporozoite titers and inhibitory activity in the case of one antiserum indicates that these two measures of antibody cannot always be used for predicting anti-sporozoite activity.