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Open Access Highly Accessed Research

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

Keith Limbach12*, Joao Aguiar12, Kalpana Gowda1, Noelle Patterson12, Esteban Abot12, Martha Sedegah1, John Sacci3 and Thomas Richie1

Author Affiliations

1 U.S. Military Malaria Vaccine Program, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD, USA

2 Henry M. Jackson Foundation for the Advancement of Military Medicine, 1401 Rockville Pike (Suite 600), Rockville, MD, USA

3 Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA

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Malaria Journal 2011, 10:65  doi:10.1186/1475-2875-10-65

Published: 16 March 2011

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.