A human monoclonal antibody blocks malaria transmission and defines a highly conserved neutralizing epitope on gametes - Archive ouverte HAL Access content directly
Journal Articles Nature Communications Year : 2021

A human monoclonal antibody blocks malaria transmission and defines a highly conserved neutralizing epitope on gametes

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Abstract

Malaria elimination requires tools that interrupt parasite transmission. Here, we characterize B cell receptor responses among Malian adults vaccinated against the first domain of the cysteine-rich 230 kDa gamete surface protein Pfs230, a key protein in sexual stage development of P. falciparum parasites. Among nine Pfs230 human monoclonal antibodies (mAbs) that we generated, one potently blocks transmission to mosquitoes in a complementdependent manner and reacts to the gamete surface; the other eight show only low or no blocking activity. The structure of the transmission-blocking mAb in complex with vaccine antigen reveals a large discontinuous conformational epitope, specific to domain 1 of Pfs230 and comprising six structural elements in the protein. The epitope is conserved, suggesting the transmission-blocking mAb is broadly functional. This study provides a rational basis to improve malaria vaccines and develop therapeutic antibodies for malaria elimination.
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Origin : Publication funded by an institution

Dates and versions

inserm-03832287 , version 1 (27-10-2022)

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Camila H Coelho, Wai Kwan Tang, Martin Burkhardt, Jacob D Galson, Olga Muratova, et al.. A human monoclonal antibody blocks malaria transmission and defines a highly conserved neutralizing epitope on gametes. Nature Communications, 2021, 12 (1), pp.1750. ⟨10.1038/s41467-021-21955-1⟩. ⟨inserm-03832287⟩

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