Analysis of the diverse antigenic landscape of the malaria protein RH5 identifies a potent vaccine-induced human public antibody clonotype.

Autor:	Barrett JR; Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK., Pipini D; Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK., Wright ND; Centre for Medicines Discovery, University of Oxford, Oxford OX3 7FZ, UK., Cooper AJR; Antibody Biology Unit, Laboratory of Immunogenetics, NIAID/NIH, Rockville, MD 20852, USA., Gorini G; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK., Quinkert D; Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK., Lias AM; Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK., Davies H; Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK., Rigby CA; Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK., Aleshnick M; Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006, USA., Williams BG; Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK., Bradshaw WJ; Centre for Medicines Discovery, University of Oxford, Oxford OX3 7FZ, UK., Paterson NG; Diamond Light Source Ltd., Harwell Science and Innovation Campus, Didcot, Oxfordshire OX11 0DE, UK., Martinson T; Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006, USA., Kirtley P; Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006, USA., Picard L; Department of Biological Engineering, MIT, Cambridge, MA, USA., Wiggins CD; Department of Biological Engineering, MIT, Cambridge, MA, USA., Donnellan FR; Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK., King LDW; Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK., Wang LT; Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK; Antibody Biology Unit, Laboratory of Immunogenetics, NIAID/NIH, Rockville, MD 20852, USA., Popplewell JF; Carterra, 825 N. 300 W. Ste. C309, Salt Lake City, UT 84103, USA., Silk SE; Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK., de Ruiter Swain J; Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK., Skinner K; Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK., Kotraiah V; Leidos Life Sciences, Frederick, MD, USA., Noe AR; Leidos Life Sciences, Frederick, MD, USA., MacGill RS; Center for Vaccine Innovation and Access, PATH, Washington, DC 20001, USA., King CR; Center for Vaccine Innovation and Access, PATH, Washington, DC 20001, USA., Birkett AJ; Center for Vaccine Innovation and Access, PATH, Washington, DC 20001, USA., Soisson LA; USAID, 1300 Pennsylvania Avenue NW, Washington, DC 20004, USA., Minassian AM; Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK., Lauffenburger DA; Department of Biological Engineering, MIT, Cambridge, MA, USA., Miura K; Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, MD 20852, USA., Long CA; Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, MD 20852, USA., Wilder BK; Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006, USA., Koekemoer L; Centre for Medicines Discovery, University of Oxford, Oxford OX3 7FZ, UK., Tan J; Antibody Biology Unit, Laboratory of Immunogenetics, NIAID/NIH, Rockville, MD 20852, USA., Nielsen CM; Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK., McHugh K; Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK., Draper SJ; Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK; The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK. Electronic address: simon.draper@bioch.ox.ac.uk.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2024 Sep 05; Vol. 187 (18), pp. 4964-4980.e21. Date of Electronic Publication: 2024 Jul 25.
DOI:	10.1016/j.cell.2024.06.015
Abstrakt:	The highly conserved and essential Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) has emerged as the leading target for vaccines against the disease-causing blood stage of malaria. However, the features of the human vaccine-induced antibody response that confer highly potent inhibition of malaria parasite invasion into red blood cells are not well defined. Here, we characterize 236 human IgG monoclonal antibodies, derived from 15 donors, induced by the most advanced PfRH5 vaccine. We define the antigenic landscape of this molecule and establish that epitope specificity, antibody association rate, and intra-PfRH5 antibody interactions are key determinants of functional anti-parasitic potency. In addition, we identify a germline IgG gene combination that results in an exceptionally potent class of antibody and demonstrate its prophylactic potential to protect against P. falciparum parasite challenge in vivo. This comprehensive dataset provides a framework to guide rational design of next-generation vaccines and prophylactic antibodies to protect against blood-stage malaria. Competing Interests: Declaration of interests J.R.B., A.J.R.C., G.G., B.G.W., L.D.W.K., L.T.W., J.T., K. McHugh, and S.J.D. are inventors on patent applications relating to RH5 malaria vaccines and/or antibodies. A.M.M. and S.J.D. have consulted to GSK on malaria vaccines. A.M.M. has an immediate family member who is an inventor on patent applications relating to RH5 malaria vaccines and antibodies. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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