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bioRxivImmunologyPreprint

A high affinity human monoclonal antibody against Pfs230 binds multiple parasite stages and blocks oocyst formation in mosquitoes

C. H. Coelho, W. K. Tang, M. Burkhardt, J. D. Galson, O. Muratova, N. Salinas, T. L. Alves e Silva, K. Reiter, N. MacDonald, V. Nguyen, M. Byrne-Steele, W. Pan, X. Hou, B. Brown, M. Eisenhower, J. Han, B. Jenkins, J. Y. A. Doritchamou, M. Smelkinson, J. Vega-Rodriguez, J. Truck, J. J. Taylor, I. Sagara, J. Renn, N. Tolia, P. Duffy

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Abstract

Malaria elimination requires tools that interrupt parasite transmission. Here, we characterized B cell receptor responses among Malian adults vaccinated against the first domain of the cysteine-rich 230kDa gamete surface protein Pfs2301-3 to neutralize sexual stage P. falciparum parasites and halt their further spread. We generated nine Pfs230 human monoclonal antibodies (mAbs). One mAb potently blocked transmission to mosquitoes in a complement-dependent manner and reacted strongly to gamete surface while eight mAbs showed only low or no blocking activity. This study provides a rational basis to improve malaria vaccines and develop therapeutic antibodies for malaria elimination.

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