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Human Antibodies that Slow Erythrocyte Invasion Potentiate Malaria-Neutralizing Antibodies.
Alanine, Daniel G W; Quinkert, Doris; Kumarasingha, Rasika; Mehmood, Shahid; Donnellan, Francesca R; Minkah, Nana K; Dadonaite, Bernadeta; Diouf, Ababacar; Galaway, Francis; Silk, Sarah E; Jamwal, Abhishek; Marshall, Jennifer M; Miura, Kazutoyo; Foquet, Lander; Elias, Sean C; Labbé, Geneviève M; Douglas, Alexander D; Jin, Jing; Payne, Ruth O; Illingworth, Joseph J; Pattinson, David J; Pulido, David; Williams, Barnabas G; de Jongh, Willem A; Wright, Gavin J; Kappe, Stefan H I; Robinson, Carol V; Long, Carole A; Crabb, Brendan S; Gilson, Paul R; Higgins, Matthew K; Draper, Simon J.
Affiliation
  • Alanine DGW; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK; Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
  • Quinkert D; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
  • Kumarasingha R; Burnet Institute, 85 Commercial Road, Melbourne, VIC 3004, Australia.
  • Mehmood S; Department of Chemistry, University of Oxford, Oxford OX1 3QZ, UK.
  • Donnellan FR; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
  • Minkah NK; Center for Global Infectious Disease Research, Seattle Children's Research Institute, 307 Westlake Ave. N., #500, Seattle, WA 98109, USA.
  • Dadonaite B; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
  • Diouf A; Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, MD 20852, USA.
  • Galaway F; Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
  • Silk SE; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
  • Jamwal A; Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
  • Marshall JM; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
  • Miura K; Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, MD 20852, USA.
  • Foquet L; Center for Global Infectious Disease Research, Seattle Children's Research Institute, 307 Westlake Ave. N., #500, Seattle, WA 98109, USA.
  • Elias SC; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
  • Labbé GM; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
  • Douglas AD; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
  • Jin J; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
  • Payne RO; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
  • Illingworth JJ; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
  • Pattinson DJ; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
  • Pulido D; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
  • Williams BG; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
  • de Jongh WA; ExpreS(2)ion Biotechnologies, SCION-DTU Science Park, Agern Allé 1, Hørsholm 2970, Denmark.
  • Wright GJ; Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
  • Kappe SHI; Center for Global Infectious Disease Research, Seattle Children's Research Institute, 307 Westlake Ave. N., #500, Seattle, WA 98109, USA.
  • Robinson CV; Department of Chemistry, University of Oxford, Oxford OX1 3QZ, UK.
  • Long CA; Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, MD 20852, USA.
  • Crabb BS; Burnet Institute, 85 Commercial Road, Melbourne, VIC 3004, Australia.
  • Gilson PR; Burnet Institute, 85 Commercial Road, Melbourne, VIC 3004, Australia.
  • Higgins MK; Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. Electronic address: matthew.higgins@bioch.ox.ac.uk.
  • Draper SJ; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK. Electronic address: simon.draper@ndm.ox.ac.uk.
Cell ; 178(1): 216-228.e21, 2019 06 27.
Article in En | MEDLINE | ID: mdl-31204103
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Plasmodium falciparum / Antibodies, Protozoan / Malaria, Falciparum / Malaria Vaccines / Erythrocytes / Antibodies, Neutralizing / Antibodies, Monoclonal Limits: Adolescent / Adult / Animals / Female / Humans / Male / Middle aged Language: En Journal: Cell Year: 2019 Type: Article Affiliation country: United kingdom
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Plasmodium falciparum / Antibodies, Protozoan / Malaria, Falciparum / Malaria Vaccines / Erythrocytes / Antibodies, Neutralizing / Antibodies, Monoclonal Limits: Adolescent / Adult / Animals / Female / Humans / Male / Middle aged Language: En Journal: Cell Year: 2019 Type: Article Affiliation country: United kingdom