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Infection and Immunity, May 2003, p. 2356-2364, Vol. 71, No. 5
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.5.2356-2364.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Oral Immunization with a Recombinant Malaria Protein Induces Conformational Antibodies and Protects Mice against Lethal Malaria

Lina Wang,¹ Lukasz Kedzierski,^1, Steven L. Wesselingh,^2,3 and Ross L. Coppel^1,4*

Department of Microbiology,¹ Victorian Bioinformatics Consortium,² Department of Medicine, Monash University, Clayton, Victoria 3800,³ Infectious Diseases Unit, Alfred Hospital, Prahran, Victoria 3181, Australia⁴

Received 21 August 2002/ Returned for modification 13 December 2002/ Accepted 9 January 2003

The increasing death toll from malaria, due to the decreasing effectiveness of current prophylactic and therapeutic regimens, has sparked a search for alternative methods of control, such as vaccines. Although several single proteins have shown some promise as subunit vaccines against sexual blood stages in experimental systems, it is clear that multicomponent vaccines are required. Many logistic difficulties make such an approach prohibitively expensive. In an effort to try to overcome some of these issues, we examined the possibility of oral immunization as a route for inducing host protective immunity. We report here that oral feeding of a malaria protein induced serum antibody levels similar to those induced by intraperitoneal immunization with Freund's adjuvant. Further, responses to conformational epitopes were induced. In the rodent challenge system, significant levels of protection to lethal challenge with malaria were induced in mice. The protective efficacy was highly correlated with antibody levels, which depended on the antigen dosage and required cholera toxin subunit B as an oral adjuvant. These findings offer new approaches to the development of a malaria vaccine and provide justification for the investigation of transgenic plants as a means of vaccine delivery.

Editor: J. M. Mansfield

Present address: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.

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