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Science 15 April 1988:
Vol. 240. no. 4850, pp. 336 - 338
DOI: 10.1126/science.3281260
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Articles

Science, Vol 240, Issue 4850, 336-338
Copyright © 1988 by American Association for the Advancement of Science

articles

Oral Salmonella typhimurium vaccine expressing circumsporozoite protein protects against malaria

JC Sadoff, WR Ballou, LS Baron, WR Majarian, RN Brey, WT Hockmeyer, JF Young, SJ Cryz, J Ou, GH Lowell, and al. et

Department of Bacterial Diseases, Walter Reed Army Institute of Research, Washington, DC 20307-5100.

Immunization with radiation-attenuated malaria sporozoites induces potent cellular immune responses, but the target antigens are unknown and have not previously been elicited by subunit vaccines prepared from the circumsporozoite (CS) protein. A method is described here for inducing protective cell-mediated immunity to sporozoites by immunization with attenuated Salmonella typhimurium transformed with the Plasmodium berghei CS gene. These transformants constitutively express CS antigens and, when used to immunize mice orally, colonize the liver, induce antigen-specific cell-mediated immunity, and protect mice against sporozoite challenge in the absence of antisporozoite antibodies. These data indicate that the CS protein contains T cell epitopes capable of inducing protective cell-mediated immunity, and emphasize the importance of proper antigen presentation in generating this response. Analogous, orally administered vaccines against human malaria might be feasible.


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