IMMUNOGENICITY OF PLASMODIUM-FALCIPARUM AND PLASMODIUM-VIVAX CIRCUMSPOROZOITE PROTEIN REPEAT MULTIPLE ANTIGEN CONSTRUCTS (MAC)

In this study we characterized the immunogenic properties of three dif ferent multispecies multiple antigen constructs (MACs) carrying the ci rcumsporozoite protein (CSP) repeats of human malaria parasites, Plasm odium falciparum and P. vivax We synthesized tetrameric MACs containin g the antigenic repents from the CSP of P. vivax-like parasite in two aims and CSP repeat sequences of either P. vivax type-1 (vivax-like/vi vax type-1 MAC), P. vivax type-2 (vivax-like/vivax type-2 MAC); or P. falciparum (vivax-like/falciparum MAC) in the other two arms. Mice of four different genetic backgrounds (H-2(a), H-2(h), H-2(d) and H-2(k)) were immunized with these MACs in Freund's adjuvant. All thr-ee MAC p reparations were found to elicit antibodies to P. vivax-like CSP repea ts in B10.BR, B10.A, and C57BL/6 mice. On the other hand, in B10.D2 mi ce only vivax-like/vivax type-1 MAC, but not the other two MACs induce d antibodies to the P. vivax-like CSP repeats. In mice immunized with vivax-like/vivax type-1 MAC, antibodies to P. vivax type-1 CS repent p eptides were induced in B10.BR, B10.A, and C57BL/6 mice, but not in B1 0.D2 mice. Antibody responses to P. vivax type-2 repeats were not indu ced in any of the four strains of mice that were immunized with vivax- like/vivax type-2 MAC. While B10.BR, B10.A, and C57BL/6 mice produced antibodies to NANP repeats of P. falciparum CSP following immunization with vivax-like/falciparum MAC, B10.D2 mice failed to elicit antibodi es to this repeat. All the sera that showed positive reactivity to pep tides in enzyme-linked immunosorbent assay were found to react with sp orozoites by IFA. In conclusion, these results showed that naturally i mmunogenic epitopes from different species of malaria parasites can be incorporated in a single vaccine construct to induce immune responses against multiple epitopes. (C) 1998 Elsevier-Science Ltd. All rights reserved.