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

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Title:Enhancing the immunogenicity of a P. falciparum MSP1-19 malaria vaccine using a putative MSP1-33 T helper epitope
Authors:Hokama, Acasia
Contributors:Hui, George (advisor)
Microbiology (department)
merozoite surface protein
Date Issued:May 2015
Publisher:University of Hawaii at Manoa
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.
Pages/Duration:42 pages
Rights:All UHM Honors Projects are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission from the copyright owner.
Appears in Collections: Honors Projects for Microbiology

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