Potent antibody lineage against malaria transmission elicited by human vaccination with Pfs25

Brandon McLeod, Kazutoyo Miura, Stephen W. Scally, Alexandre Bosch, Ngan Nguyen, Hanjun Shin, Dongkyoon Kim, Wayne Volkmuth, Sebastian Rämisch, Jessica A. Chichester, Stephen Streatfield, Colleen Woods, William R. Schief, Daniel Emerling, C. Richter King and Jean-Philippe Julien ()
Additional contact information
Brandon McLeod: The Hospital for Sick Children Research Institute
Kazutoyo Miura: National Institutes of Health
Stephen W. Scally: The Hospital for Sick Children Research Institute
Alexandre Bosch: The Hospital for Sick Children Research Institute
Ngan Nguyen: Atreca
Hanjun Shin: Atreca
Dongkyoon Kim: Atreca
Wayne Volkmuth: Atreca
Sebastian Rämisch: The Scripps Research Institute
Jessica A. Chichester: The University of Pennsylvania
Stephen Streatfield: Fraunhofer USA Center for Molecular Biotechnology CMB
Colleen Woods: PATH’s Malaria Vaccine Initiative
William R. Schief: The Scripps Research Institute
Daniel Emerling: Atreca
C. Richter King: PATH’s Malaria Vaccine Initiative
Jean-Philippe Julien: The Hospital for Sick Children Research Institute

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: Abstract Transmission-blocking vaccines have the potential to be key contributors to malaria elimination. Such vaccines elicit antibodies that inhibit parasites during their development in Anopheles mosquitoes, thus breaking the cycle of transmission. To date, characterization of humoral responses to Plasmodium falciparum transmission-blocking vaccine candidate Pfs25 has largely been conducted in pre-clinical models. Here, we present molecular analyses of human antibody responses generated in a clinical trial evaluating Pfs25 vaccination. From a collection of monoclonal antibodies with transmission-blocking activity, we identify the most potent transmission-blocking antibody yet described against Pfs25; 2544. The interactions of 2544 and three other antibodies with Pfs25 are analyzed by crystallography to understand structural requirements for elicitation of human transmission-blocking responses. Our analyses provide insights into Pfs25 immunogenicity and epitope potency, and detail an affinity maturation pathway for a potent transmission-blocking antibody in humans. Our findings can be employed to guide the design of improved malaria transmission-blocking vaccines.

Date: 2019
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DOI: 10.1038/s41467-019-11980-6

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