Superior antibody immunogenicity of a viral-vectored RH5 blood-stage malaria vaccine in Tanzanian infants as compared to adults.

Translation to humans

Journal

Med (New York, N.Y.)
ISSN: 2666-6340
Titre abrégé: Med
Pays: United States
ID NLM: 101769215

Informations de publication

Date de publication:
13 Oct 2023
Historique:
received: 14 04 2023
revised: 23 06 2023
accepted: 11 07 2023
pubmed: 13 8 2023
medline: 13 8 2023
entrez: 12 8 2023
Statut: ppublish

Résumé

RH5 is a leading blood-stage candidate antigen for a Plasmodium falciparum vaccine; however, its safety and immunogenicity in malaria-endemic populations are unknown. A phase 1b, single-center, dose-escalation, age-de-escalation, double-blind, randomized, controlled trial was conducted in Bagamoyo, Tanzania (NCT03435874). Between 12 Vaccinations were well tolerated, with profiles comparable across groups. No serious adverse events were reported. Vaccination induced RH5-specific cellular and humoral responses. Higher anti-RH5 serum immunoglobulin G (IgG) responses were observed post boost in young children and infants compared to adults. Vaccine-induced antibodies showed growth inhibition activity (GIA) in vitro against P. falciparum blood-stage parasites; their highest levels were observed in infants. The ChAd63-MVA RH5 vaccine shows acceptable safety and reactogenicity and encouraging immunogenicity in children and infants residing in a malaria-endemic area. The levels of functional GIA observed in RH5-vaccinated infants are the highest reported to date following human vaccination. These data support onward clinical development of RH5-based blood-stage vaccines to protect against clinical malaria in young African infants. Medical Research Council, London, UK.

Sections du résumé

BACKGROUND BACKGROUND
RH5 is a leading blood-stage candidate antigen for a Plasmodium falciparum vaccine; however, its safety and immunogenicity in malaria-endemic populations are unknown.
METHODS METHODS
A phase 1b, single-center, dose-escalation, age-de-escalation, double-blind, randomized, controlled trial was conducted in Bagamoyo, Tanzania (NCT03435874). Between 12
FINDINGS RESULTS
Vaccinations were well tolerated, with profiles comparable across groups. No serious adverse events were reported. Vaccination induced RH5-specific cellular and humoral responses. Higher anti-RH5 serum immunoglobulin G (IgG) responses were observed post boost in young children and infants compared to adults. Vaccine-induced antibodies showed growth inhibition activity (GIA) in vitro against P. falciparum blood-stage parasites; their highest levels were observed in infants.
CONCLUSIONS CONCLUSIONS
The ChAd63-MVA RH5 vaccine shows acceptable safety and reactogenicity and encouraging immunogenicity in children and infants residing in a malaria-endemic area. The levels of functional GIA observed in RH5-vaccinated infants are the highest reported to date following human vaccination. These data support onward clinical development of RH5-based blood-stage vaccines to protect against clinical malaria in young African infants.
FUNDING BACKGROUND
Medical Research Council, London, UK.

Identifiants

DOI: 10.1016/j.medj.2023.07.003 PMID: 37572659
pubmed: 37572659
pii: S2666-6340(23)00226-X
doi: 10.1016/j.medj.2023.07.003
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

668-686.e7

Informations de copyright

Copyright © 2023. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of interests S.J.D. is a named inventor on patent applications relating to RH5 malaria vaccines and adenovirus-based vaccines, is an inventor on intellectual property licensed by Oxford University Innovation to AstraZeneca, 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 adenovirus-based vaccines, and is an inventor on intellectual property licensed by Oxford University Innovation to AstraZeneca.

Auteurs

Sarah E Silk (SE)

Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford OX1 3QU, UK; Centre for Clinical Vaccinology and Tropical Medicine, Jenner Institute, University of Oxford, Old Road Campus, Oxford OX3 7LE, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford OX1 3QU, UK.

Wilmina F Kalinga (WF)

Interventions and Clinical Trials Department, Ifakara Health Institute, P.O. Box 74, Bagamoyo, Tanzania.

Ivanny M Mtaka (IM)

Interventions and Clinical Trials Department, Ifakara Health Institute, P.O. Box 74, Bagamoyo, Tanzania.

Nasoro S Lilolime (NS)

Interventions and Clinical Trials Department, Ifakara Health Institute, P.O. Box 74, Bagamoyo, Tanzania.

Maximillian Mpina (M)

Interventions and Clinical Trials Department, Ifakara Health Institute, P.O. Box 74, Bagamoyo, Tanzania.

Florence Milando (F)

Interventions and Clinical Trials Department, Ifakara Health Institute, P.O. Box 74, Bagamoyo, Tanzania.

Saumu Ahmed (S)

Interventions and Clinical Trials Department, Ifakara Health Institute, P.O. Box 74, Bagamoyo, Tanzania.

Ababacar Diouf (A)

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

Fatuma Mkwepu (F)

Interventions and Clinical Trials Department, Ifakara Health Institute, P.O. Box 74, Bagamoyo, Tanzania.

Beatus Simon (B)

Interventions and Clinical Trials Department, Ifakara Health Institute, P.O. Box 74, Bagamoyo, Tanzania.

Thabit Athumani (T)

Interventions and Clinical Trials Department, Ifakara Health Institute, P.O. Box 74, Bagamoyo, Tanzania.

Mohammed Rashid (M)

Interventions and Clinical Trials Department, Ifakara Health Institute, P.O. Box 74, Bagamoyo, Tanzania.

Latipha Mohammed (L)

Interventions and Clinical Trials Department, Ifakara Health Institute, P.O. Box 74, Bagamoyo, Tanzania.

Omary Lweno (O)

Interventions and Clinical Trials Department, Ifakara Health Institute, P.O. Box 74, Bagamoyo, Tanzania.

Ali M Ali (AM)

Interventions and Clinical Trials Department, Ifakara Health Institute, P.O. Box 74, Bagamoyo, Tanzania.

Gloria Nyaulingo (G)

Interventions and Clinical Trials Department, Ifakara Health Institute, P.O. Box 74, Bagamoyo, Tanzania.

Bakari Mwalimu (B)

Interventions and Clinical Trials Department, Ifakara Health Institute, P.O. Box 74, Bagamoyo, Tanzania.

Sarah Mswata (S)

Interventions and Clinical Trials Department, Ifakara Health Institute, P.O. Box 74, Bagamoyo, Tanzania.

Tunu G Mwamlima (TG)

Interventions and Clinical Trials Department, Ifakara Health Institute, P.O. Box 74, Bagamoyo, Tanzania.

Jordan R Barrett (JR)

Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford OX1 3QU, UK; Centre for Clinical Vaccinology and Tropical Medicine, Jenner Institute, University of Oxford, Old Road Campus, Oxford OX3 7LE, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford OX1 3QU, UK.

Lawrence T Wang (LT)

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

Yrene Themistocleous (Y)

Centre for Clinical Vaccinology and Tropical Medicine, Jenner Institute, University of Oxford, Old Road Campus, Oxford OX3 7LE, UK.

Lloyd D W King (LDW)

Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford OX1 3QU, UK; Centre for Clinical Vaccinology and Tropical Medicine, Jenner Institute, University of Oxford, Old Road Campus, Oxford OX3 7LE, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford OX1 3QU, UK.

Susanne H Hodgson (SH)

Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford OX1 3QU, UK; Centre for Clinical Vaccinology and Tropical Medicine, Jenner Institute, University of Oxford, Old Road Campus, Oxford OX3 7LE, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford OX1 3QU, UK.

Ruth O Payne (RO)

Centre for Clinical Vaccinology and Tropical Medicine, Jenner Institute, University of Oxford, Old Road Campus, Oxford OX3 7LE, UK.

Carolyn M Nielsen (CM)

Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford OX1 3QU, UK; Centre for Clinical Vaccinology and Tropical Medicine, Jenner Institute, University of Oxford, Old Road Campus, Oxford OX3 7LE, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford OX1 3QU, UK.

Alison M Lawrie (AM)

Centre for Clinical Vaccinology and Tropical Medicine, Jenner Institute, University of Oxford, Old Road Campus, Oxford OX3 7LE, UK.

Fay L Nugent (FL)

Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford OX1 3QU, UK; Centre for Clinical Vaccinology and Tropical Medicine, Jenner Institute, University of Oxford, Old Road Campus, Oxford OX3 7LE, UK.

Jee-Sun Cho (JS)

Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford OX1 3QU, UK; Centre for Clinical Vaccinology and Tropical Medicine, Jenner Institute, University of Oxford, Old Road Campus, Oxford OX3 7LE, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford OX1 3QU, UK.

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.

Simon J Draper (SJ)

Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford OX1 3QU, UK; Centre for Clinical Vaccinology and Tropical Medicine, Jenner Institute, University of Oxford, Old Road Campus, Oxford OX3 7LE, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford OX1 3QU, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK.

Angela M Minassian (AM)

Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford OX1 3QU, UK; Centre for Clinical Vaccinology and Tropical Medicine, Jenner Institute, University of Oxford, Old Road Campus, Oxford OX3 7LE, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford OX1 3QU, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK. Electronic address: angela.minassian@bioch.ox.ac.uk.

Ally I Olotu (AI)

Interventions and Clinical Trials Department, Ifakara Health Institute, P.O. Box 74, Bagamoyo, Tanzania.

Classifications MeSH