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First published online September 23, 2003

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The Journal of Experimental Biology 206, 3789-3802 (2003)
doi: 10.1242/jeb.00615

Review Article

Utilization of genomic sequence information to develop malaria vaccines

D. L. Doolan^1,2,*, J. C. Aguiar^1,3, W. R. Weiss¹, A. Sette⁵, P. L. Felgner⁶, D. P. Regis¹, P. Quinones-Casas^1,4, J. R. Yates, III⁷, P. L. Blair¹, T. L. Richie¹, S. L. Hoffman^1, and D. J. Carucci¹

¹ Malaria Program, Naval Medical Research Center, Silver Spring, MD 20910-7500, USA
² Department of Molecular Microbiology and Immunology, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, MD 21205-2179, USA
³ Pan American Health Organization, Washington, DC 20910, USA
⁴ Henry M. Jackson Foundation, Rockville, MD 20852, USA
⁵ La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA
⁶ University of California Irvine, Irvine, CA 92697, USA
⁷ The Scripps Research Institute, La Jolla, CA 92037, USA

^* Author for correspondence (e-mail: dooland{at}nmrc.navy.mil)

Accepted 21 July 2003

Recent advances in the fields of genomics, proteomics and molecular immunology offer tremendous opportunities for the development of novel interventions against public health threats, including malaria. However, there is currently no algorithm that can effectively identify the targets of protective T cell or antibody responses from genomic data. Furthermore, the identification of antigens that will stimulate the most effective immunity against the target pathogen is problematic, particularly if the genome is large. Malaria is an attractive model for the development and validation of approaches to translate genomic information to vaccine development because of the critical need for effective anti-malarial interventions and because the Plasmodium parasite is a complex multistage pathogen targeted by multiple immune responses. Sterile protective immunity can be achieved by immunization with radiation-attenuated sporozoites, and anti-disease immunity can be induced in residents in malaria-endemic areas. However, the 23 Mb Plasmodium falciparum genome encodes more than 5300 proteins, each of which is a potential target of protective immune responses. The current generation of subunit vaccines is based on a single or few antigens and therefore might elicit too narrow a breadth of response. We are working towards the development of a new generation vaccine based on the presumption that duplicating the protection induced by the whole organism may require a vaccine nearly as complex as the organism itself. Here, we present our strategy to exploit the genomic sequence of P. falciparum for malaria vaccine development.

Key words: Plasmodium, P. falciparum, vaccine, genomics, proteomics, molecular immunology, immune screening, multi-epitope

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