Syracuse

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

Archive ouverte

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

Edité par CCSD ; Nature Publishing Group -

International audience. 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.

• Description
• Sujet/Public
• Outil
• Outil d'anticipation
• Mémoire et thèse
• Gestion