TY - JOUR
T1 - A human monoclonal antibody blocks malaria transmission and defines a highly conserved neutralizing epitope on gametes
AU - Coelho, Camila H.
AU - Tang, Wai Kwan
AU - Burkhardt, Martin
AU - Galson, Jacob D.
AU - Muratova, Olga
AU - Salinas, Nichole D.
AU - Alves e Silva, Thiago Luiz
AU - Reiter, Karine
AU - MacDonald, Nicholas J.
AU - Nguyen, Vu
AU - Herrera, Raul
AU - Shimp, Richard
AU - Narum, David L.
AU - Byrne-Steele, Miranda
AU - Pan, Wenjing
AU - Hou, Xiaohong
AU - Brown, Brittany
AU - Eisenhower, Mary
AU - Han, Jian
AU - Jenkins, Bethany J.
AU - Doritchamou, Justin Y.A.
AU - Smelkinson, Margery G.
AU - Vega-Rodríguez, Joel
AU - Trück, Johannes
AU - Taylor, Justin J.
AU - Sagara, Issaka
AU - Renn, Jonathan P.
AU - Tolia, Niraj H.
AU - Duffy, Patrick E.
N1 - Publisher Copyright:
© 2021, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85102902686&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-21955-1
DO - 10.1038/s41467-021-21955-1
M3 - Article
C2 - 33741942
AN - SCOPUS:85102902686
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1750
ER -