Evaluation of the Immunogenicity and Vaccine Potential of Recombinant Plasmodium falciparum Merozoite Surface Protein 8

Abstract

ABSTRACT The C-terminal 19-kDa domain of merozoite surface protein 1 (MSP1 19 ) is the target of protective antibodies but alone is poorly immunogenic. Previously, using the Plasmodium yoelii murine model, we fused P. yoelii MSP1 19 ( Py MSP1 19 ) with full-length P. yoelii merozoite surface protein 8 (MSP8). Upon immunization, the MSP8-restricted T cell response provided help for the production of high and sustained levels of protective Py MSP1 19 - and Py MSP8-specific antibodies. Here, we assessed the vaccine potential of MSP8 of the human malaria parasite, Plasmodium falciparum . Distinct from Py MSP8, P. falciparum MSP8 ( Pf MSP8) contains an N-terminal asparagine and aspartic acid (Asn/Asp)-rich domain whose function is unknown. Comparative analysis of recombinant full-length Pf MSP8 and a truncated version devoid of the Asn/Asp-rich domain, Pf MSP8(ΔAsn/Asp), showed that both proteins were immunogenic for T cells and B cells. All T cell epitopes utilized mapped within r Pf MSP8(ΔAsn/Asp). The dominant B cell epitopes were conformational and common to both r Pf MSP8 and r Pf MSP8(ΔAsn/Asp). Analysis of native Pf MSP8 expression revealed that Pf MSP8 is present intracellularly in late schizonts and merozoites. Following invasion, Pf MSP8 is found distributed on the surface of ring- and trophozoite-stage parasites. Consistent with a low and/or transient expression of Pf MSP8 on the surface of merozoites, Pf MSP8-specific rabbit IgG did not inhibit the in vitro growth of P. falciparum blood-stage parasites. These studies suggest that the further development of Pf MSP8 as a malaria vaccine component should focus on the use of Pf MSP8(ΔAsn/Asp) and its conserved, immunogenic T cell epitopes as a fusion partner for protective domains of poor immunogens, including Pf MSP1 19 .