Journal article
Human Antibodies that Slow Erythrocyte Invasion Potentiate Malaria-Neutralizing Antibodies
DGW Alanine, D Quinkert, R Kumarasingha, S Mehmood, FR Donnellan, NK Minkah, B Dadonaite, A Diouf, F Galaway, SE Silk, A Jamwal, JM Marshall, K Miura, L Foquet, SC Elias, GM Labbé, AD Douglas, J Jin, RO Payne, JJ Illingworth Show all
Cell | CELL PRESS | Published : 2019
Abstract
The Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) is the leading target for next-generation vaccines against the disease-causing blood-stage of malaria. However, little is known about how human antibodies confer functional immunity against this antigen. We isolated a panel of human monoclonal antibodies (mAbs) against PfRH5 from peripheral blood B cells from vaccinees in the first clinical trial of a PfRH5-based vaccine. We identified a subset of mAbs with neutralizing activity that bind to three distinct sites and another subset of mAbs that are non-functional, or even antagonistic to neutralizing antibodies. We also identify the epitope of a novel group of non-neutra..
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Grants
Awarded by United States Agency for International Development
Funding Acknowledgements
The authors thank Julie Furze, Kathryn Hjerrild, Andrew Worth, Amelia Lias, Robert Ragotte, Oliver Lyth, Rebecca Dabbs, and Catherine Cherry (Jenner Institute, University of Oxford) for assistance; Kate Wright (Biochemistry Department, University of Oxford) for PfRH5 Delta NL; Zenon Zenonos (Wellcome Trust Sanger Institute) for chimeric mAb reagents; Patrick C. Wilson (University of Chicago) for expression plasmids; Oleg Fedorov (Structural Genomics Consortium, University of Oxford) for use of the Octet RED384; Ed Lowe and Pietro Roversi (Biochemistry Department, University of Oxford) for crystallographic dataset collection; Amy Duckett and Carly Banner (University of Oxford) for arranging contracts; and all the VAC057 PfRH5 vaccine clinical trial study volunteers. This work was supported by the European Union Seventh Framework Programme (FP7/2007-2013) grant MultiMalVax (305282), the Wellcome Trust (206194), and the European Union's Horizon 2020 research and innovation programme grant OptiMalVax (733273). GIA work was supported by the United States Agency for International Development (USAID) and the Intramural Program of the NIH, National Institute of Allergy and Infectious Diseases. S.M. and C.V.R. were funded by UK MRC programme (MR/N020413/1) and Wellcome Trust Instrument Grant (104923/Z/14/Z) for the HDX-MS platform. P.R.G. and R.K. were funded by NHMRC (1092789 for live-cell imaging). D.G.W.A. and B.G.W. hold UK MRC iCASE PhD Studentships (MR/K017632/1) and (MR/N013468/1). B.D. holds and J.J.I. held a PhD studentship in the Wellcome Trust Infection, Immunology and Translational Medicine PhD Programme (105399/Z/14/Z). A.D.D. holds a Wellcome Trust Early Postdoctoral Research Training Fellowship for Clinicians (201477/Z/16/Z). M.K.H. is a Wellcome Trust Senior Investigator (101020/Z/13/Z). S.J.D. is a Jenner Investigator, a Lister Institute Research Prize Fellow, and a Wellcome Trust Senior Fellow (106917/Z/15/Z).