Primary and Secondary Responses to (NANP) Peptides by Plasmodium falciparum Sporozoites in Various Strains of Mice

Abstract

The repetitive epitope (Asn-Ala-Asn-Pro=NANP) of the Plasmodium falciparum circumsporozoite protein is considered as the basis for the development of a recombinant or synthetic subunit vaccine against malaria. Vaccines consisting of (NANP)_n molecules coupled to carrier proteins have already been tested in trials in human volunteers with partial success. In this paper we show that C57BL/6 mice, genetically responsive to carrier-free (NANP)_n molecules, exhibit a secondary antibody response to (NANP) if they are primed with carrier-free (NANP)₄₀ synthetic peptide, and then challenged with P. falciparum sporozoites However, such a sporozoite-mediated boosting effect is not observed if C57BL/6 and BALB/c mice were previously primed with (NANP)₄₀ peptide conjugated to carrier proteins the genetic restriction of the murine antibody response to (NANP)_n is overcome when mice bearing seven different H-2 haplotypes are immunized with entire P. falciparum sporozoites. These results may have implications for the understanding of natural or induced anti-sporozoite immunity, and show that the use of T-cell epitopes from the plasmodial antigenic repertoire would be very likely to represent an efficient approach for the development of a subunit malaria vaccine.