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- Title
A human monoclonal antibody blocks malaria transmission and defines a highly conserved neutralizing epitope on gametes.
- Authors
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.
- 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. Vaccines that interrupt malaria transmission will be important tools for malaria elimination. Here the authors identify a human monoclonal antibody from Pfs230 vaccinated individuals that blocks transmission of Plasmodium falciparum to mosquitoes in a complement-dependent manner and reacts with gamete surface.
- Subjects
MONOCLONAL antibodies; GAMETES; B cell receptors; MALARIA; CYTOSKELETAL proteins; MALARIA vaccines; VACCINATION
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-21955-1