Natural malaria infection elicits rare but potent neutralizing antibodies to the blood-stage antigen RH5.

Plasmodium falciparum RH5 malaria monoclonal antibodies natural infection vaccine design

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
17 Jul 2024
Historique:
received: 15 09 2023
revised: 15 04 2024
accepted: 26 06 2024
medline: 27 7 2024
pubmed: 27 7 2024
entrez: 26 7 2024
Statut: aheadofprint

Résumé

Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is the most advanced blood-stage malaria vaccine candidate and is being evaluated for efficacy in endemic regions, emphasizing the need to study the underlying antibody response to RH5 during natural infection, which could augment or counteract responses to vaccination. Here, we found that RH5-reactive B cells were rare, and circulating immunoglobulin G (IgG) responses to RH5 were short-lived in malaria-exposed Malian individuals, despite repeated infections over multiple years. RH5-specific monoclonal antibodies isolated from eight malaria-exposed individuals mostly targeted non-neutralizing epitopes, in contrast to antibodies isolated from five RH5-vaccinated, malaria-naive UK individuals. However, MAD8-151 and MAD8-502, isolated from two malaria-exposed Malian individuals, were among the most potent neutralizers out of 186 antibodies from both cohorts and targeted the same epitopes as the most potent vaccine-induced antibodies. These results suggest that natural malaria infection may boost RH5-vaccine-induced responses and provide a clear strategy for the development of next-generation RH5 vaccines.

Identifiants

DOI: 10.1016/j.cell.2024.06.037 PMID: 39059381
pubmed: 39059381
pii: S0092-8674(24)00711-6
doi: 10.1016/j.cell.2024.06.037
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of interests J.T., L.T.W., and A.J.R.C. are co-inventors on a provisional patent filed on the mAbs described in this study. J.R.B., K.M., M.K.H., and S.J.D. are inventors on patent applications relating to RH5 malaria vaccines and/or antibodies. A.M.M. has an immediate family member who is an inventor on patent applications relating to RH5 malaria vaccines and antibodies. The content of this publication does not necessarily reflect the views or policies of the DHHS or of the institutions and companies with which the authors are affiliated.

Auteurs

Lawrence T Wang (LT)

Antibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK; Medical Scientist Training Program, University of California, San Diego School of Medicine, La Jolla, CA 92093, USA.

Andrew J R Cooper (AJR)

Antibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.

Brendan Farrell (B)

Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK.

Kazutoyo Miura (K)

Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.

Ababacar Diouf (A)

Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.

Nicole Müller-Sienerth (N)

Wellcome Sanger Institute, Cambridge CB10 1SA, UK.

Cécile Crosnier (C)

Department of Biology, Hull York Medical School, York Biomedical Research Institute, University of York, Heslington, York YO10 5DD, UK.

Lauren Purser (L)

Antibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.

Payton J Kirtley (PJ)

Vaccine and Gene Therapy Institute, Oregon Health & Science University, Portland, OR 97006, USA.

Maciej Maciuszek (M)

Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.

Jordan R Barrett (JR)

Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK.

Kirsty McHugh (K)

Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK.

Rodney Ogwang (R)

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Courtney Tucker (C)

Antibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.

Shanping Li (S)

Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.

Safiatou Doumbo (S)

Mali International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Point G, BP 1805 Bamako, Mali.

Didier Doumtabe (D)

Mali International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Point G, BP 1805 Bamako, Mali.

Chul-Woo Pyo (CW)

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Jeff Skinner (J)

Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.

Carolyn M Nielsen (CM)

Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK.

Sarah E Silk (SE)

Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK.

Kassoum Kayentao (K)

Mali International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Point G, BP 1805 Bamako, Mali.

Aissata Ongoiba (A)

Mali International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Point G, BP 1805 Bamako, Mali.

Ming Zhao (M)

Protein Chemistry Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.

Doan C Nguyen (DC)

Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Emory University, Atlanta, GA 30322, USA.

F Eun-Hyung Lee (FE)

Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Emory University, Atlanta, GA 30322, USA.

Angela M Minassian (AM)

Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK; NIHR Oxford Biomedical Research Centre, Oxford OX3 9DU, UK.

Daniel E Geraghty (DE)

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Boubacar Traore (B)

Mali International Center of Excellence in Research, University of Sciences, Technique and Technology of Bamako, Point G, BP 1805 Bamako, Mali.

Robert A Seder (RA)

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Brandon K Wilder (BK)

Vaccine and Gene Therapy Institute, Oregon Health & Science University, Portland, OR 97006, USA.

Peter D Crompton (PD)

Malaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.

Gavin J Wright (GJ)

Department of Biology, Hull York Medical School, York Biomedical Research Institute, University of York, Heslington, York YO10 5DD, UK.

Carole A Long (CA)

Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.

Simon J Draper (SJ)

Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK; NIHR Oxford Biomedical Research Centre, Oxford OX3 9DU, UK.

Matthew K Higgins (MK)

Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford OX1 3QU, UK.

Joshua Tan (J)

Antibody Biology Unit, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA. Electronic address: tanj4@nih.gov.

Classifications MeSH