Cellular responses to modified Plasmodium falciparum MSP1 19 antigens in individuals previously exposed to natural malaria infection

Abstract Background MSP1 processing-inhibitory antibodies bind to epitopes on the 19 kDa C-terminal region of the Plasmodium falciparum merozoite surface protein 1 (MSP1 19 ), inhibiting erythrocyte invasion. Blocking antibodies also bind to this antigen but prevent inhibitory antibodies binding, al...

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Bibliographic Details
Published in:Malaria Journal
Main Authors: Awobode Henrietta O, Ayede Idowu, Uthaipibull Chairat, Omosun Yusuf O, Anumudu Chiaka I, Okafor Christian MF, Odaibo Alex B, Langhorne Jean, Holder Anthony A, Nwuba Roseangela I, Troye-Blomberg Marita
Format: Article in Journal/Newspaper
Language:English
Published: BMC 2009
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Online Access:https://doi.org/10.1186/1475-2875-8-263
https://doaj.org/article/7de09bbff6624ca0a0e77e5d2c96f363
Description
Summary:Abstract Background MSP1 processing-inhibitory antibodies bind to epitopes on the 19 kDa C-terminal region of the Plasmodium falciparum merozoite surface protein 1 (MSP1 19 ), inhibiting erythrocyte invasion. Blocking antibodies also bind to this antigen but prevent inhibitory antibodies binding, allowing invasion to proceed. Recombinant MSP1 19 had been modified previously to allow inhibitory but not blocking antibodies to continue to bind. Immunization with these modified proteins, therefore, has the potential to induce more effective protective antibodies. However, it was unclear whether the modification of MSP1 19 would affect critical T-cell responses to epitopes in this antigen. Methods The cellular responses to wild-type MSP1 19 and a panel of modified MSP1 19 antigens were measured using an in-vitro assay for two groups of individuals: the first were malaria-naïve and the second had been naturally exposed to Plasmodium falciparum infection. The cellular responses to the modified proteins were examined using cells from malaria-exposed infants and adults. Results Interestingly, stimulation indices (SI) for responses induced by some of the modified proteins were at least two-fold higher than those elicited by the wild-type MSP1 19 . A protein with four amino acid substitutions (Glu27→Tyr, Leu31→Arg, Tyr34→Ser and Glu43→Leu) had the highest stimulation index (SI up to 360) and induced large responses in 64% of the samples that had significant cellular responses to the modified proteins. Conclusion This study suggests that specific MSP1 19 variants that have been engineered to improve their antigenicity for inhibitory antibodies, retain T-cell epitopes and the ability to induce cellular responses. These proteins are candidates for the development of MSP1-based malaria vaccines.