Preclinical development of a stabilized RH5 virus-like particle vaccine that induces improved antimalarial antibodies.

Autor:	King LDW; Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, OX1 3QU Oxford, UK; Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, OX1 3QU Oxford, UK; The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK., Pulido D; The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK., Barrett JR; Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, OX1 3QU Oxford, UK; Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, OX1 3QU Oxford, UK; The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK., Davies H; Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, OX1 3QU Oxford, UK; Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, OX1 3QU Oxford, UK; The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK., Quinkert D; Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, OX1 3QU Oxford, UK; Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, OX1 3QU Oxford, UK; The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK., Lias AM; Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, OX1 3QU Oxford, UK; Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, OX1 3QU Oxford, UK; The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK., Silk SE; Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, OX1 3QU Oxford, UK; Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, OX1 3QU Oxford, UK; The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK., Pattinson DJ; The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK., Diouf A; Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, MD 20852, USA., Williams BG; Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, OX1 3QU Oxford, UK; Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, OX1 3QU Oxford, UK; The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK., McHugh K; Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, OX1 3QU Oxford, UK; Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, OX1 3QU Oxford, UK; The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK., Rodrigues A; Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, OX1 3QU Oxford, UK; Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, OX1 3QU Oxford, UK., Rigby CA; Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, OX1 3QU Oxford, UK; Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, OX1 3QU Oxford, UK., Strazza V; Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, OX1 3QU Oxford, UK; Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, OX1 3QU Oxford, UK., Suurbaar J; The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK; West African Centre for Cell Biology of Infectious Pathogens, University of Ghana, Accra LG 54, Ghana., Rees-Spear C; The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK; London School of Hygiene and Tropical Medicine, WC1E 7HT London, UK., Dabbs RA; The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK., Ishizuka AS; The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK., Zhou Y; The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK., Gupta G; The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK., Jin J; The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK., Li Y; The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK., Carnrot C; Novavax AB, Kungsgatan 109, 753 18 Uppsala, Sweden., Minassian AM; Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, OX1 3QU Oxford, UK; Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, OX1 3QU Oxford, UK; The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK., Campeotto I; Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, OX1 3QU Oxford, UK., Fleishman SJ; Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel., 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., Long CA; Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, MD 20852, USA., Miura K; Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, MD 20852, USA., Ashfield R; Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, OX1 3QU Oxford, UK; Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, OX1 3QU Oxford, UK; The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK., Skinner K; Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, OX1 3QU Oxford, UK; Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, OX1 3QU Oxford, UK; The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK., Howarth MR; Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, OX1 3QU Oxford, UK., Biswas S; The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK., Draper SJ; Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, OX1 3QU Oxford, UK; Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, OX1 3QU Oxford, UK; The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK. Electronic address: simon.draper@bioch.ox.ac.uk.
Jazyk:	angličtina
Zdroj:	Cell reports. Medicine [Cell Rep Med] 2024 Jul 16; Vol. 5 (7), pp. 101654.
DOI:	10.1016/j.xcrm.2024.101654
Abstrakt:	Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is a leading blood-stage malaria vaccine antigen target, currently in a phase 2b clinical trial as a full-length soluble protein/adjuvant vaccine candidate called RH5.1/Matrix-M. We identify that disordered regions of the full-length RH5 molecule induce non-growth inhibitory antibodies in human vaccinees and that a re-engineered and stabilized immunogen (including just the alpha-helical core of RH5) induces a qualitatively superior growth inhibitory antibody response in rats vaccinated with this protein formulated in Matrix-M adjuvant. In parallel, bioconjugation of this immunogen, termed "RH5.2," to hepatitis B surface antigen virus-like particles (VLPs) using the "plug-and-display" SpyTag-SpyCatcher platform technology also enables superior quantitative antibody immunogenicity over soluble protein/adjuvant in vaccinated mice and rats. These studies identify a blood-stage malaria vaccine candidate that may improve upon the current leading soluble protein vaccine candidate RH5.1/Matrix-M. The RH5.2-VLP/Matrix-M vaccine candidate is now under evaluation in phase 1a/b clinical trials. Competing Interests: Declaration of interests S.J.D. is an inventor on patent applications relating to RH5 malaria vaccines and antibodies, is a co-founder of and shareholder in SpyBiotech, and has been a consultant to GSK on malaria vaccines. A.M.M. has been a consultant to GSK on malaria vaccines, has an immediate family member who is an inventor on patent applications relating to RH5 malaria vaccines and antibodies, and is a co-founder of and shareholder in SpyBiotech. M.R.H. is an inventor on patents relating to peptide targeting via spontaneous amide bond formation and is a co-founder of and shareholder in SpyBiotech. S.B. is an inventor on patent applications relating to vaccines made using spontaneous amide bond formation and is a co-founder of, shareholder in, and employee of SpyBiotech. J.J. is an inventor on patent applications relating to vaccines made using spontaneous amide bond formation and is a co-founder of and shareholder in SpyBiotech. R.A.D. is an inventor on patent applications relating to vaccines made using spontaneous amide bond formation and shareholder in SpyBiotech. L.D.W.K., J.R.B., D.Q., A.M.L., S.E.S., B.G.W., K. McHugh, I.C., S.J.F., and D.P. are inventors on patent applications relating to RH5 malaria vaccines and/or antibodies. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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