The structure of Plasmodium yoelii merozoite surface protein 119, antibody specificity and implications for malaria vaccine design
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...
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The Royal Society
2014-01-01
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Series: | Open Biology |
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Online Access: | https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.130091 |
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author | Rachel D. Curd Berry Birdsall Madhusudan Kadekoppala Solabomi A. Ogun Geoffrey Kelly Anthony A. Holder |
author_facet | Rachel D. Curd Berry Birdsall Madhusudan Kadekoppala Solabomi A. Ogun Geoffrey Kelly Anthony A. Holder |
author_sort | Rachel D. Curd |
collection | DOAJ |
description | 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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institution | Directory Open Access Journal |
issn | 2046-2441 |
language | English |
last_indexed | 2024-04-13T10:54:39Z |
publishDate | 2014-01-01 |
publisher | The Royal Society |
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series | Open Biology |
spelling | doaj.art-8959a13c7aa4422bbf4029ebaf086f612022-12-22T02:49:34ZengThe Royal SocietyOpen Biology2046-24412014-01-014110.1098/rsob.130091130091The structure of Plasmodium yoelii merozoite surface protein 119, antibody specificity and implications for malaria vaccine designRachel D. CurdBerry BirdsallMadhusudan KadekoppalaSolabomi A. OgunGeoffrey KellyAnthony A. HolderMerozoite 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.https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.130091malaria vaccinemsp1 structureplasmodium |
spellingShingle | Rachel D. Curd Berry Birdsall Madhusudan Kadekoppala Solabomi A. Ogun Geoffrey Kelly Anthony A. Holder The structure of Plasmodium yoelii merozoite surface protein 119, antibody specificity and implications for malaria vaccine design Open Biology malaria vaccine msp1 structure plasmodium |
title | The structure of Plasmodium yoelii merozoite surface protein 119, antibody specificity and implications for malaria vaccine design |
title_full | The structure of Plasmodium yoelii merozoite surface protein 119, antibody specificity and implications for malaria vaccine design |
title_fullStr | The structure of Plasmodium yoelii merozoite surface protein 119, antibody specificity and implications for malaria vaccine design |
title_full_unstemmed | The structure of Plasmodium yoelii merozoite surface protein 119, antibody specificity and implications for malaria vaccine design |
title_short | The structure of Plasmodium yoelii merozoite surface protein 119, antibody specificity and implications for malaria vaccine design |
title_sort | structure of plasmodium yoelii merozoite surface protein 119 antibody specificity and implications for malaria vaccine design |
topic | malaria vaccine msp1 structure plasmodium |
url | https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.130091 |
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