Journal Article

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

Duffy, Patrick E., Coelho, Camila H., Doritchamou, Justin Y. A., Herrera, Raul, Salinas, Nichole D., Han, Jian, Smelkinson, Margery G., Burkhardt, Martin, Tolia, Niraj H., Nguyen, Vu, Byrne-Steele, Miranda, Brown, Brittany, MacDonald, Nicholas J., Alves e Silva, Thiago Luiz, Pan, Wenjing, Hou, Xiaohong, Narum, David L., Trück, Johannes, Taylor, Justin J., Reiter, Karine, Jenkins, Bethany J., Sagara, Issaka, Healy, Sara A., Galson, Jacob D., Shimp, Richard, Eisenhower, Mary, Muratova, Olga, Renn, Jonathan P., Tang, Wai Kwan, Vega-Rodríguez, Joel

2021

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 101/1 / 13/1 / 13/31 / 38/1 / 38/47 / 38/77 / 45/23 / 631/250/590/2294 / 631/326/417/2546 / Adult / Animals / Antibodies, Monoclonal - immunology / Antibodies, Monoclonal - pharmacology / Antibodies, Protozoan - immunology / Antibodies, Protozoan - pharmacology / Antigens / Antigens, Protozoan - chemistry / Antigens, Protozoan - immunology / Aquatic insects / Binding Sites / Cells, Cultured / Culicidae / Developmental stages / Disease transmission / Domains / Epitopes / Epitopes - chemistry / Epitopes - immunology / Gametes / Germ Cells - immunology / Host-Parasite Interactions - drug effects / Host-Parasite Interactions - immunology / Humanities and Social Sciences / Humans / Life Sciences / Malaria / Malaria Vaccines - administration & dosage / Malaria Vaccines - immunology / Malaria, Falciparum - parasitology / Malaria, Falciparum - prevention & control / Malaria, Falciparum - transmission / Monoclonal antibodies / Mosquito Vectors - parasitology / Mosquitoes / multidisciplinary / Parasites / Plasmodium falciparum - drug effects / Plasmodium falciparum - immunology / Plasmodium falciparum - physiology / Protein Conformation / Proteins / Protozoan Proteins - chemistry / Protozoan Proteins - immunology / Santé publique et épidémiologie / Science / Science (multidisciplinary) / Structural members / Vaccines / Vector-borne diseases