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

Animals Malaria Vaccines / immunology Antibodies, Protozoan / immunology Plasmodium falciparum / immunology Vaccines, Virus-Like Particle / immunology Humans Mice Protozoan Proteins / immunology Rats Malaria, Falciparum / prevention & control Antigens, Protozoan / immunology Female Carrier Proteins / immunology Mice, Inbred BALB C
Plasmodium falciparum RH5 VLP antibody blood-stage malaria vaccine virus-like particle

Journal

Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894

Informations de publication

Date de publication:
16 Jul 2024
Historique:
received: 05 01 2024
revised: 12 04 2024
accepted: 19 06 2024
medline: 18 7 2024
pubmed: 18 7 2024
entrez: 17 7 2024
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.xcrm.2024.101654 PMID: 39019011
pubmed: 39019011
pii: S2666-3791(24)00368-9
doi: 10.1016/j.xcrm.2024.101654
pii:
doi:

Substances chimiques

Malaria Vaccines 0
Antibodies, Protozoan 0
Vaccines, Virus-Like Particle 0
Protozoan Proteins 0
RH5 protein, Plasmodium falciparum 0
Antigens, Protozoan 0
Carrier Proteins 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

101654

Informations de copyright

Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

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.

Auteurs

Lloyd D W 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.

David Pulido (D)

The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK.

Jordan R 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.

Hannah 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.

Doris 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.

Amelia M 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.

Sarah E 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.

David J Pattinson (DJ)

The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK.

Ababacar Diouf (A)

Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, MD 20852, USA.

Barnabas G 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.

Kirsty 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.

Ana 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.

Cassandra A 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.

Veronica 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.

Jonathan 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.

Chloe 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.

Rebecca A Dabbs (RA)

The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK.

Andrew S Ishizuka (AS)

The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK.

Yu Zhou (Y)

The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK.

Gaurav Gupta (G)

The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK.

Jing Jin (J)

The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK.

Yuanyuan Li (Y)

The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK.

Cecilia Carnrot (C)

Novavax AB, Kungsgatan 109, 753 18 Uppsala, Sweden.

Angela M 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.

Ivan Campeotto (I)

Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, OX1 3QU Oxford, UK.

Sarel J Fleishman (SJ)

Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.

Amy R Noe (AR)

Leidos Life Sciences, Frederick, MD, USA.

Randall S MacGill (RS)

Center for Vaccine Innovation and Access, PATH, Washington, DC 20001, USA.

C Richter King (CR)

Center for Vaccine Innovation and Access, PATH, Washington, DC 20001, USA.

Ashley J Birkett (AJ)

Center for Vaccine Innovation and Access, PATH, Washington, DC 20001, USA.

Lorraine A Soisson (LA)

USAID, 1300 Pennsylvania Avenue NW, Washington, DC 20004, USA.

Carole A Long (CA)

Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, MD 20852, USA.

Kazutoyo Miura (K)

Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, MD 20852, USA.

Rebecca 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.

Katherine 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.

Mark R Howarth (MR)

Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, OX1 3QU Oxford, UK.

Sumi Biswas (S)

The Jenner Institute, University of Oxford, Old Road Campus Research Building, OX3 7DQ Oxford, UK.

Simon J 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.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Preclinical development of a stabilized RH5...
questionsmedicales.fr › Mélanges complexes › Produits biologiques › Vaccins › Vaccins antiprotozoaires › Vaccins contre le paludisme › Preclinical development of a stabilized RH5...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps antiprotozoaires › Preclinical development of a stabilized RH5...
questionsmedicales.fr › Eucaryotes › Alveolata › Apicomplexa › Haemosporida › Plasmodium › Plasmodium falciparum › Preclinical development of a stabilized RH5...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Vaccins synthétiques › Vaccins à pseudo-particules virales › Preclinical development of a stabilized RH5...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Preclinical development of a stabilized RH5...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Preclinical development of a stabilized RH5...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de protozoaire › Preclinical development of a stabilized RH5...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › Preclinical development of a stabilized RH5...
questionsmedicales.fr › Infection › Maladies vectorielles › Paludisme › Paludisme à Plasmodium falciparum › Preclinical development of a stabilized RH5...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Antigènes de protozoaire › Preclinical development of a stabilized RH5...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de transport › Preclinical development of a stabilized RH5...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée BALB C › Preclinical development of a stabilized RH5...