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

Camila H. Coelho, Wai Kwan Tang, Martin Burkhardt, Jacob D. Galson, Olga Muratova, Nichole D. Salinas, Thiago Luiz Alves e Silva, Karine Reiter, Nicholas J. MacDonald, Vu Nguyen, Raul Herrera, Richard Shimp, David L. Narum, Miranda Byrne-Steele, Wenjing Pan, Xiaohong Hou, Brittany Brown, Mary Eisenhower, Jian Han, Bethany J. Jenkins, Justin Y. A. Doritchamou, Margery G. Smelkinson, Joel Vega-Rodríguez, Johannes Trück, Justin J. Taylor, Issaka Sagara, Sara A. Healy, Jonathan P. Renn, Niraj H. Tolia () and Patrick E. Duffy ()
Additional contact information
Camila H. Coelho: National Institutes of Health
Wai Kwan Tang: National Institutes of Health
Martin Burkhardt: National Institutes of Health
Jacob D. Galson: Division of Immunology and Children’s Research Center, University Children’s Hospital Zurich, University of Zurich (UZH)
Olga Muratova: National Institutes of Health
Nichole D. Salinas: National Institutes of Health
Thiago Luiz Alves e Silva: National Institutes of Health
Karine Reiter: National Institutes of Health
Nicholas J. MacDonald: National Institutes of Health
Vu Nguyen: National Institutes of Health
Raul Herrera: National Institutes of Health
Richard Shimp: National Institutes of Health
David L. Narum: National Institutes of Health
Miranda Byrne-Steele: iRepertoire Inc.
Wenjing Pan: iRepertoire Inc.
Xiaohong Hou: iRepertoire Inc.
Brittany Brown: iRepertoire Inc.
Mary Eisenhower: iRepertoire Inc.
Jian Han: iRepertoire Inc.
Bethany J. Jenkins: National Institutes of Health
Justin Y. A. Doritchamou: National Institutes of Health
Margery G. Smelkinson: National Institutes of Health
Joel Vega-Rodríguez: National Institutes of Health
Johannes Trück: Division of Immunology and Children’s Research Center, University Children’s Hospital Zurich, University of Zurich (UZH)
Justin J. Taylor: Fred Hutchinson Cancer Research Center
Issaka Sagara: University of Sciences, Techniques, and Technology
Sara A. Healy: National Institutes of Health
Jonathan P. Renn: National Institutes of Health
Niraj H. Tolia: National Institutes of Health
Patrick E. Duffy: National Institutes of Health

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-21955-1

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