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

Sarah E Silk; Wilmina F Kalinga; Ivanny M Mtaka; Nasoro S Lilolime; Maximillian Mpina; Florence Milando; Saumu Ahmed; Ababacar Diouf; Fatuma Mkwepu; Beatus Simon; Thabit Athumani; Mohammed Rashid; Latipha Mohammed; Omary Lweno; Ali M Ali; Gloria Nyaulingo; Bakari Mwalimu; Sarah Mswata; Tunu G Mwamlima; Jordan R Barrett; Lawrence T Wang; Yrene Themistocleous; Lloyd D W King; Susanne H Hodgson; Ruth O Payne; Carolyn M Nielsen; Alison M Lawrie; Fay L Nugent; Jee-Sun Cho; Carole A Long; Kazutoyo Miura; Simon J Draper; Angela M Minassian; Ally I Olotu

doi:10.1016/j.medj.2023.07.003

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

Med. 2023 Oct 13;4(10):668-686.e7. doi: 10.1016/j.medj.2023.07.003. Epub 2023 Aug 11.

Authors

Sarah E Silk¹, Wilmina F Kalinga², Ivanny M Mtaka², Nasoro S Lilolime², Maximillian Mpina², Florence Milando², Saumu Ahmed², Ababacar Diouf³, Fatuma Mkwepu², Beatus Simon², Thabit Athumani², Mohammed Rashid², Latipha Mohammed², Omary Lweno², Ali M Ali², Gloria Nyaulingo², Bakari Mwalimu², Sarah Mswata², Tunu G Mwamlima², Jordan R Barrett¹, Lawrence T Wang⁴, Yrene Themistocleous⁵, Lloyd D W King¹, Susanne H Hodgson¹, Ruth O Payne⁵, Carolyn M Nielsen¹, Alison M Lawrie⁵, Fay L Nugent⁶, Jee-Sun Cho¹, Carole A Long³, Kazutoyo Miura³, Simon J Draper⁷, Angela M Minassian⁸, Ally I Olotu²

Affiliations

¹ 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.
² Interventions and Clinical Trials Department, Ifakara Health Institute, P.O. Box 74, Bagamoyo, Tanzania.
³ Laboratory of Malaria and Vector Research, NIAID/NIH, Rockville, MD 20852, USA.
⁴ 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.
⁵ Centre for Clinical Vaccinology and Tropical Medicine, Jenner Institute, University of Oxford, Old Road Campus, Oxford OX3 7LE, UK.
⁶ 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.
⁷ 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.
⁸ 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.

PMID: 37572659
DOI: 10.1016/j.medj.2023.07.003

Abstract

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: A phase 1b, single-center, dose-escalation, age-de-escalation, double-blind, randomized, controlled trial was conducted in Bagamoyo, Tanzania (NCT03435874). Between 12^th April and 25^th October 2018, 63 healthy adults (18-35 years), young children (1-6 years), and infants (6-11 months) received a priming dose of viral-vectored ChAd63 RH5 or rabies control vaccine. Sixty participants were boosted with modified vaccinia virus Ankara (MVA) RH5 or rabies control vaccine 8 weeks later and completed 6 months of follow-up post priming. Primary outcomes were the number of solicited and unsolicited adverse events post vaccination and the number of serious adverse events over the study period. Secondary outcomes included measures of the anti-RH5 immune response.

Findings: 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: 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: Medical Research Council, London, UK.

Keywords: Translation to humans.

Publication types

Clinical Trial, Phase I
Randomized Controlled Trial

MeSH terms

Adenoviruses, Simian
Adolescent
Adult
Antibodies, Viral
Child
Child, Preschool
Double-Blind Method
Humans
Infant
Malaria Vaccines* / adverse effects
Malaria Vaccines* / immunology
Malaria, Falciparum* / prevention & control
Rabies
Tanzania
Young Adult

Substances

Antibodies, Viral
Malaria Vaccines

Supplementary concepts

chimpanzee adenovirus serotype 63

Grants and funding

MR/P020593/1/MRC_/Medical Research Council/United Kingdom