Enhancing the immunogenicity of a P. falciparum MSP1-19 malaria vaccine using a putative MSP1-33 T helper epitope

Abstract

Developing an efficacious vaccine for the vector-borne infectious disease, Malaria, remains a top priority for disease control. The P. falciparum Merozoite Surface Protein 1(MSP1) is a leading blood-stage malaria vaccine candidate, and anti-MSP1 antibodies have been found to be important in providing protection against blood infections. MSP1 (195 kDa) goes through a number of proteolytic cleavage events to produce a 42-kDa fragment, which is further cleaved into 33-kDa (MSP1-33) and 19-kDa (MSP1-19) fragments. Although antibodies against MSP1-19 are protective, the MSP1-19 molecule alone cannot induce broad immune responsiveness due to lack of T helper epitopes on this protein fragment. We have recently identified four putative T epitopes on MSP1-33 that may enhance the quantity and quality of antibody responses to MSP1-19. We hypothesize that selective inclusion of one or more of these epitopes will have a measurable effect on the immunogenicity of MSP1-19. As proof of principle, we chose one of these epitopes to construct a new MSP1 vaccine by linking it to MSP1-19 via recombinant protein expression approach. The ability of this epitope to enhance the immunogenicity of MSP1-19 was examined in outbred mice in terms of production of high antibody titer, parasite growth inhibitory antibodies, and broad vaccine responsiveness. The recombinant protein tested produced a higher percentage of antibody responders than the native protein. The levels of Il-4 produced by antigen stimulation inferred that a TH2 response was also stimulated. These studies will hopefully lead to a rational approach to develop a more effective human malaria MSP1-42 vaccine.