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Structural basis for recognition of the malaria vaccine candidate Pfs48/45 by a transmission blocking antibody

DOI: 10.1038/s41467-018-06340-9 DOI Help

Authors: Frank Lennartz (University of Oxford) , Florian Brod (University of Oxford) , Rebecca Dabbs (University of Oxford) , Kazutoyo Miura (National Institute of Allergy and Infectious Diseases) , David Mekhaiel (University of Oxford) , Arianna Marini (University of Oxford) , Matthijs Jore (Radboud University Medical Centre) , Max M. Søgaard (ExpreS2ion Biotechnologies) , Thomas Jørgensen (ExpreS2ion Biotechnologies) , Willem A. De Jongh (ExpreS2ion Biotechnologies) , Robert W. Sauerwein (Radboud University Medical Centre) , Carole A. Long (National Institute of Allergy and Infectious Diseases) , Sumi Biswas (University of Oxford) , Matthew Higgins (University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 9

State: Published (Approved)
Published: September 2018
Diamond Proposal Number(s): 18069

Open Access Open Access

Abstract: The quest to develop an effective malaria vaccine remains a major priority in the fight against global infectious disease. An approach with great potential is a transmission-blocking vaccine which induces antibodies that prevent establishment of a productive infection in mosquitos that feed on infected humans, thereby stopping the transmission cycle. One of the most promising targets for such a vaccine is the gamete surface protein, Pfs48/45. Here we establish a system for production of full-length Pfs48/45 and use this to raise a panel of monoclonal antibodies. We map the binding regions of these antibodies on Pfs48/45 and correlate the location of their epitopes with their transmission-blocking activity. Finally, we present the structure of the C-terminal domain of Pfs48/45 bound to the most potent transmission-blocking antibody, and provide key molecular information for future structure-guided immunogen design.

Journal Keywords: malaria vaccine

Subject Areas: Medicine


Instruments: I03-Macromolecular Crystallography

Documents:
s41467-018-06340-9.pdf