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Plasmodium vivax malaria in man: anti-disease and transmission blocking immunity

Objective



Two different aspects of immunity to human plasmodium vivax malaria will be explored. (1) Anti-disease immunity and (2) Transmission blocking immunity.

1) In residents of malaria endemic regions, repeated infections lead to a decrease in the severity of disease. This clinical immunity is distinct from, and appears before immunity directed against the parasite itself. The proposers have demonstrated that clinical paroxysms in P.vivax malaria i.e., periodic episodes of fever with chills and rigors, are accompanied by a transient but massive rise in serum TNF levels. Further, during paroxysms, TNF acting in conjunction with other as yet unidentified complementary serum factor(s) mediate killing of intraerythrocytic malaria parasites. Both serum TNF levels and other parasite killing factor(s) are significantly reduced in clinically immune subjects, suggesting that they are associated with clinical disease. There is evidence that clinical immunity is achieved by maintaining these cytokines at a low level; this is by the acquisition of antibodies which neutralize parasite antigens that induce the production of these cytokines. It is the purpose of this proposal to study disease and clinical immunity to P.vivax in humans With the objectives of identifying parasite antigens that induce cytokines associated with disease. This could form the basis of an "anti-disease" vaccine against malaria.

2) Another approach to vaccination against malaria is to immunize against the sexual stages which mediate transmission of the parasite from man to mosquito. Using monoclonal antibodies, we have identified several targets of such "transmission blocking immunity" in P.vivax. Epitopes involved in this immunity are dependent on tertiary conformational structure which cannot be reproduced in recombinant polypeptides expressed in bacteria. This hinders the cloning of the corresponding genes. Here we propose to use a eukaryotic expression system, COS cells, to overcome this problem and screen for cells expressing transmission blocking vaccine candidates by "panning" with our transmission blocking immune reagents.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

UNIVERSITY OF EDINBURGH
Address
King's Building, Darwing Building, Mayfield Road
EH9 3Jr Edinburgh
United Kingdom

Participants (2)

Institut Pasteur
France
Address
25 Rue Du Docteur Roux
75724 Paris
University of Colombo
Sri Lanka
Address
Kynsey Road
8 Colombo