Differential non-Responsiveness in Humans of Candidate Plasmodium Falciparum Vaccine Antigens

Isabella A. QuakyiNational Institutes of Health, Medical Research Council Laboratories, The Gambia; and Georgetown University, Bethesda, Maryland

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Lizbeth N. OtooNational Institutes of Health, Medical Research Council Laboratories, The Gambia; and Georgetown University, Bethesda, Maryland

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David PomboNational Institutes of Health, Medical Research Council Laboratories, The Gambia; and Georgetown University, Bethesda, Maryland

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Lavencia Y. SugarsNational Institutes of Health, Medical Research Council Laboratories, The Gambia; and Georgetown University, Bethesda, Maryland

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Arun MenonNational Institutes of Health, Medical Research Council Laboratories, The Gambia; and Georgetown University, Bethesda, Maryland

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Anne S. DeGrootNational Institutes of Health, Medical Research Council Laboratories, The Gambia; and Georgetown University, Bethesda, Maryland

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Armead JohnsonNational Institutes of Health, Medical Research Council Laboratories, The Gambia; and Georgetown University, Bethesda, Maryland

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David AllingNational Institutes of Health, Medical Research Council Laboratories, The Gambia; and Georgetown University, Bethesda, Maryland

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Louis H. MillerNational Institutes of Health, Medical Research Council Laboratories, The Gambia; and Georgetown University, Bethesda, Maryland

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Michael F. GoodNational Institutes of Health, Medical Research Council Laboratories, The Gambia; and Georgetown University, Bethesda, Maryland

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Synthetic subunit vaccines to sporozoites, merozoites, and gametes are being developed for malaria. The vaccine strategy assumes that the population to be immunized will respond favorably to these vaccine antigens. Using sera of 35 adults and 50 children from the The Gambia, West Africa, where Plasmodium falciparum is highly endemic, we examined the humoral immune response to candidate malaria vaccine antigens from sporozoites, merozoites, and gametes. We observed widespread restricted immunogenicity to defined parasite antigens in children and adults. HLA typing of adult lymphocytes demonstrated a marked diversity in HLA haplotypes in this population. Our results and those from our studies in mice suggest that genetic factors may partly explain the immunological non-responsiveness. This may necessitate re-evaluation of the malaria vaccine strategy.

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