| Literature DB >> 33741942 |
Camila H Coelho1, Wai Kwan Tang2, Martin Burkhardt3, Jacob D Galson4,5, Olga Muratova3, Nichole D Salinas2, Thiago Luiz Alves E Silva6, Karine Reiter3, Nicholas J MacDonald3, Vu Nguyen3, Raul Herrera3, Richard Shimp3, David L Narum3, Miranda Byrne-Steele7, Wenjing Pan7, Xiaohong Hou7, Brittany Brown7, Mary Eisenhower7, Jian Han7, Bethany J Jenkins1, Justin Y A Doritchamou1, Margery G Smelkinson8, Joel Vega-Rodríguez6, Johannes Trück4, Justin J Taylor9, Issaka Sagara10, Sara A Healy3, Jonathan P Renn3, Niraj H Tolia11, Patrick E Duffy12,13.
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 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.Entities:
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Year: 2021 PMID： 33741942 PMCID： PMC7979743 DOI： 10.1038/s41467-021-21955-1
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 17.694