Human antibodies that slow erythrocyte invasion potentiate malaria-neutralizing antibodies

DOI: 10.1016/j.cell.2019.05.025

Authors: Daniel G. W. Alanine (The Jenner Institute, University of Oxford) , Doris Quinkert (The Jenner Institute, University of Oxford) , Rasika Kumarasingha (Burnet Institute) , Shahid Mehmood (University of Oxford) , Francesca R. Donnellan (The Jenner Institute, University of Oxford) , Nana K. Minkah (Seattle Children’s Research Institute) , Bernadeta Dadonaite (The Jenner Institute, University of Oxford) , Ababacar Diouf (NIAID/NIH) , Francis Galaway (Wellcome Trust Sanger Institute) , Sarah E. Silk (The Jenner Institute, University of Oxford) , Abhishek Jamwal (University of Oxford) , Jennifer M. Marshall (The Jenner Institute, University of Oxford) , Kazutoyo Miura (NIAID/NIH) , Lander Foquet (Seattle Children’s Research Institute) , Sean C. Elias (The Jenner Institute, University of Oxford) , Geneviève M. Labbé (The Jenner Institute, University of Oxford) , Alexander D. Douglas (The Jenner Institute, University of Oxford) , Jing Jin (The Jenner Institute, University of Oxford) , Ruth O. Payne (The Jenner Institute, University of Oxford) , Joseph J. Illingworth (The Jenner Institute, University of Oxford) , David J. Pattinson (The Jenner Institute, University of Oxford) , David Pulido (The Jenner Institute, University of Oxford) , Barnabas G. Williams (The Jenner Institute, University of Oxford) , Willem A. De Jongh (ExpreS2ion Biotechnologies) , Gavin J. Wright (Wellcome Trust Sanger Institute) , Stefan H. I. Kappe (Seattle Children’s Research Institute) , Carol V. Robinson (University of Oxford) , Carole A. Long (NIAID/NIH) , Brendan S. Crabb (Burnet Institute) , Paul R. Gilson (Burnet Institute) , Matthew Higgins (University of Oxford) , Simon J. Draper (The Jenner Institute, University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Cell

State: Published (Approved)
Published: June 2019
Diamond Proposal Number(s): 18069

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-neutralizing antibodies that significantly reduce the speed of red blood cell invasion by the merozoite, thereby potentiating the effect of all neutralizing PfRH5 antibodies as well as synergizing with antibodies targeting other malaria invasion proteins. Our results provide a roadmap for structure-guided vaccine development to maximize antibody efficacy against blood-stage malaria.

Journal Keywords: malaria; blood-stagemerozoite; structural vaccinology; RH5; synergy; monoclonal antibody; neutralization; X-ray crystallography; live-cell microscopy

Diamond Keywords: Malaria

Subject Areas: Biology and Bio-materials, Medicine


Instruments: I03-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength) , I04-Macromolecular Crystallography

Added On: 19/06/2019 11:25

Documents:
mgf444.pdf

Discipline Tags:

Vaccines Infectious Diseases Disease in the Developing World Health & Wellbeing Structural biology Drug Discovery Life Sciences & Biotech Parasitology

Technical Tags:

Diffraction Macromolecular Crystallography (MX)