Identification of two new protective pre-erythrocytic malaria vaccine antigen candidates

US Military Malaria Vaccine Program, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD, USA.
Malaria Journal (Impact Factor: 3.11). 03/2011; 10(1):65. DOI: 10.1186/1475-2875-10-65
Source: PubMed


Despite years of effort, a licensed malaria vaccine is not yet available. One of the obstacles facing the development of a malaria vaccine is the extensive heterogeneity of many of the current malaria vaccine antigens. To counteract this antigenic diversity, an effective malaria vaccine may need to elicit an immune response against multiple malaria antigens, thereby limiting the negative impact of variability in any one antigen. Since most of the malaria vaccine antigens that have been evaluated in people have not elicited a protective immune response, there is a need to identify additional protective antigens. In this study, the efficacy of three pre-erythrocytic stage malaria antigens was evaluated in a Plasmodium yoelii/mouse protection model.
Mice were immunized with plasmid DNA and vaccinia virus vectors that expressed one, two or all three P. yoelii vaccine antigens. The immunized mice were challenged with 300 P. yoelii sporozoites and evaluated for subsequent infection.
Vaccines that expressed any one of the three antigens did not protect a high percentage of mice against a P. yoelii challenge. However, vaccines that expressed all three antigens protected a higher percentage of mice than a vaccine that expressed PyCSP, the most efficacious malaria vaccine antigen. Dissection of the multi-antigen vaccine indicated that protection was primarily associated with two of the three P. yoelii antigens. The protection elicited by a vaccine expressing these two antigens exceeded the sum of the protection elicited by the single antigen vaccines, suggesting a potential synergistic interaction.
This work identifies two promising malaria vaccine antigen candidates and suggests that a multi-antigen vaccine may be more efficacious than a single antigen vaccine.

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    • "Sedegah et al [43] studied protection using only Vaxfectin with a CSP DNA construct that lacked the MIP3α component and obtained maximum bloodstream protection of 54%, similar to what we observed with that construct, but clearly less than the 80–100% protection observed with the addition of the MIP3α component. In a more recent trial, Limbach et al. [91] could protect only 57% of mice challenged intravenously with 300 P. yoelii sporozoites after immunization with plasmid DNA followed by a vaccinia virus vector boost that expressed one, two or three different P. yoelii vaccine antigens. In one of the few studies to show a high level of protection, Scheiblhofer et al. demonstrated that DNA immunization with a CSP construct from which the glycosylphosphatidylinositol signal sequence was deleted elicited 100% protection of Balb/c mice from intradermal challenge with P. berghei [92]. "
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