The structure of Plasmodium yoelii merozoite surface protein 119, antibody specificity and implications for malaria vaccine design |
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Authors: | Rachel D. Curd Berry Birdsall Madhusudan Kadekoppala Solabomi A. Ogun Geoffrey Kelly Anthony A. Holder |
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Affiliation: | 1.Divisions of Parasitology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK;2.Molecular Structure, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK;3.NMR Centre, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK |
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Abstract: | Merozoite surface protein 1 (MSP1) has been identified as a target antigen for protective immune responses against asexual blood stage malaria, but effective vaccines based on MSP1 have not been developed so far. We have modified the sequence of Plasmodium yoelii MSP119 (the C-terminal region of the molecule) and examined the ability of the variant proteins to bind protective monoclonal antibodies and to induce protection by immunization. In parallel, we examined the structure of the protein and the consequences of the amino acid changes. Naturally occurring sequence polymorphisms reduced the binding of individual protective antibodies, indicating that they contribute to immune evasion, but immunization with these variant proteins still provided protective immunity. One variant that resulted in the localized distortion of a loop close to the N-terminus of MSP119 almost completely ablated protection by immunization, indicating the importance of this region of MSP119 as a target for protective immunity and in vaccine development. |
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Keywords: | malaria vaccine MSP1 structure plasmodium |
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