6RCO

PfRH5-binding monoclonal antibody R5.004

Summary for 6RCO

• Entry DOI: 10.2210/pdb6rco/pdb
• Descriptor: R5.004 heavy chain, R5.004 light chain, GLYCEROL, ... (5 entities in total)
• Functional Keywords: plasmodium falciparum erythrocyte invasion neutralisation human monoclonal antibody, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 4
• Total formula weight: 96021.60

Authors

Alanine, D.G.W.,Draper, S.J.,Higgins, M.K. (deposition date: 2019-04-11, release date: 2019-06-26, Last modification date: 2024-10-23)

Primary citation

Alanine, D.G.W.,Quinkert, D.,Kumarasingha, R.,Mehmood, S.,Donnellan, F.R.,Minkah, N.K.,Dadonaite, B.,Diouf, A.,Galaway, F.,Silk, S.E.,Jamwal, A.,Marshall, J.M.,Miura, K.,Foquet, L.,Elias, S.C.,Labbe, G.M.,Douglas, A.D.,Jin, J.,Payne, R.O.,Illingworth, J.J.,Pattinson, D.J.,Pulido, D.,Williams, B.G.,de Jongh, W.A.,Wright, G.J.,Kappe, S.H.I.,Robinson, C.V.,Long, C.A.,Crabb, B.S.,Gilson, P.R.,Higgins, M.K.,Draper, S.J.
Human Antibodies that Slow Erythrocyte Invasion Potentiate Malaria-Neutralizing Antibodies.
Cell, 178:216-228.e21, 2019

PubMed 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.

PubMed: 31204103
DOI: 10.1016/j.cell.2019.05.025

Experimental method

X-RAY DIFFRACTION (1.66 Å)