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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Main Authors: Rachel D. Curd, Berry Birdsall, Madhusudan Kadekoppala, Solabomi A. Ogun, Geoffrey Kelly, Anthony A. Holder
Format: Article
Language:English
Published: The Royal Society 2014-01-01
Series:Open Biology
Subjects:
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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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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