Nature communications · 2021
A human monoclonal antibody blocks malaria transmission and defines a highly conserved neutralizing epitope on gametes.
СтатьяResearch Support, N.I.H., IntramuralПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Coelho Camila H, Tang Wai Kwan, Burkhardt Martin, Galson Jacob D, Muratova Olga, Salinas Nichole D, Alves E Silva Thiago Luiz, Reiter Karine, MacDonald Nicholas J, Nguyen Vu, Herrera Raul, Shimp Richard, Narum David L, Byrne-Steele Miranda, Pan Wenjing, Hou Xiaohong, Brown Brittany, Eisenhower Mary, Han Jian, Jenkins Bethany J, Doritchamou Justin Y A, Smelkinson Margery G, Vega-Rodríguez Joel, Trück Johannes, Taylor Justin J, Sagara Issaka, Healy Sara A, Renn Jonathan P, Tolia Niraj H, Duffy Patrick E
Аннотация
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 complement-dependent 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.