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High Efficacy of a Low Dose Candidate Malaria Vaccine, R21 in 1 Adjuvant Matrix-M™, with Seasonal Administration to Children in Burkina Faso

30 Pages Posted: 20 Apr 2021

See all articles by Mehreen S. Datoo

Mehreen S. Datoo

University of Oxford - Centre for Clinical Vaccinology and Tropical Medicine

Hamtandi Magloire Natama

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Athanase Somé

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Ousmane Traoré

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Toussaint Rouamba

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Duncan Bellamy

University of Oxford - The Jenner Institute Laboratories

Prisca Yameogo

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Daniel Valia

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Moubarak Tegneri

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Florence Ouedraogo

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Rachidatou Soma

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Seydou Sawadogo

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Faizatou Sorgho

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Karim Derra

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Eli Rouamba

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Benedict Orindi

Kenya Medical Research Institute (KEMRI)

Fernando Ramos-Lopez

University of Oxford - Centre for Clinical Vaccinology and Tropical Medicine

Amy Flaxman

University of Oxford - The Jenner Institute

Federica Cappuccini

University of Oxford - The Jenner Institute

Reshma Kailath

University of Oxford - The Jenner Institute Laboratories

Sean C. Elias

University of Oxford - The Jenner Institute

Ekta Mukhopadhyay

University of Oxford - The Jenner Institute Laboratories

Andres Noe

University of Oxford - The Jenner Institute Laboratories

Matthew Cairns

London School of Hygiene & Tropical Medicine

Alison Lawrie

University of Oxford - Centre for Clinical Vaccinology and Tropical Medicine

Rachel Roberts

University of Oxford - Centre for Clinical Vaccinology and Tropical Medicine

Innocent Valéa

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Hermann Sorgho

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Nicola Williams

University of Oxford - Department of Primary Care Health Services

Gregory Glenn

Novavax

Louis Fries

Novavax

Jenny Reimer

Novavax AB

Katie J. Ewer

University of Oxford - The Jenner Institute Laboratories

Umesh Shaligram

Serum Institute of India Private Ltd

Adrian V. S. Hill

University of Oxford - The Jenner Institute; University of Oxford - Wellcome Trust Centre for Human Genetics; University of Oxford - Centre for Clinical Vaccinology and Tropical Medicine

Halidou Tinto

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

More...

Abstract

Background: Stalled progress in controlling Plasmodium falciparum malaria highlights the need for an effective and deployable vaccine. RTS,S/AS01, the most effective malaria vaccine candidate to date, demonstrated 55·8% (97·5% confidence interval [CI], 51-60) efficacy over 12 months in African children.

Methods: We conducted a double-blind, randomised, controlled trial of a low-dose circumsporozoite protein-based vaccine, R21, with two different doses of adjuvant, Matrix-M™ (MM), in children aged 5-17 months in Nanoro, Burkina Faso, a highly seasonal malaria transmission setting. Three vaccinations were administered at 4-week intervals prior to the malaria season with a fourth dose one year later. Vaccine safety, immunogenicity and efficacy were evaluated over one year.

Findings: 450 children were randomised to receive the R21/MM vaccine or a control rabies vaccine. R21/MM had a 43 favourable safety profile and was well-tolerated. At 6 months, 43/146 (29·5%) who received R21/MM with low44 dose adjuvant, 38/146 (26%) who received R21/MM with high-dose adjuvant, and 105/147 (71·4%) who received the rabies vaccine developed clinical malaria. Vaccine efficacy (VE) was 74% (95% CI, 63-82) and 77% (95% CI, 67-84) in the low- and high-dose adjuvant groups, respectively. At 1 year, VE remained high at 77% (95% CI, 67-84) in the high-dose adjuvant group. Participants vaccinated with R21/MM showed high titres of malaria-specific anti-NANP antibodies 28 days after the third vaccination, which were almost doubled with the higher adjuvant dose. Titres waned but were boosted to levels similar to peak titres following the primary series of vaccinations after a fourth dose administered one year later.

Interpretation: R21/Matrix-M appears safe and very immunogenic in African children, and demonstrates promising high-level efficacy.

Trial Registration: ClinicalTrials.gov number: NCT03896724.

Funding: The European & Developing Countries Clinical Trials Partnership (EDCTP), The Wellcome Trust and the NIHR Oxford Biomedical Research Centre.

Declaration of Interest: AVSH and KJE are named as co-inventors on patent applications related to R21. GG, LF, JR and PP-A are employees of Novavax, developers of the Matrix-M adjuvant, and US is an employee of the Serum Institute of India Private Ltd, co-developer of the R21/MM vaccine. Other authors declare no competing interests.

Ethical Approval: The trial was approved by the Comité d’Ethique pour la Recherche en Santé, Burkina Faso (CERS, reference number 2019-01-012), and by the national regulatory authority, Agence National de Régulation Pharmaceutique, Burkina Faso (ANRP, reference number 5005420193EC0000). Ethical approval was also granted in the United Kingdom by the Oxford Tropical Research Ethics Committee (OxTREC reference number 19-19).

Suggested Citation

Datoo, Mehreen S. and Magloire Natama, Hamtandi and Somé, Athanase and Traoré, Ousmane and Rouamba, Toussaint and Bellamy, Duncan and Yameogo, Prisca and Valia, Daniel and Tegneri, Moubarak and Ouedraogo, Florence and Soma, Rachidatou and Sawadogo, Seydou and Sorgho, Faizatou and Derra, Karim and Rouamba, Eli and Orindi, Benedict and Ramos-Lopez, Fernando and Flaxman, Amy and Cappuccini, Federica and Kailath, Reshma and Elias, Sean C. and Mukhopadhyay, Ekta and Noe, Andres and Cairns, Matthew and Lawrie, Alison and Roberts, Rachel and Valéa, Innocent and Sorgho, Hermann and Williams, Nicola and Glenn, Gregory and Fries, Louis and Reimer, Jenny and Ewer, Katie J. and Shaligram, Umesh and Hill, Adrian V. S. and Tinto, Halidou, High Efficacy of a Low Dose Candidate Malaria Vaccine, R21 in 1 Adjuvant Matrix-M™, with Seasonal Administration to Children in Burkina Faso (April 20, 2021). Available at SSRN: https://ssrn.com/abstract=3830681 or http://dx.doi.org/10.2139/ssrn.3830681

Mehreen S. Datoo

University of Oxford - Centre for Clinical Vaccinology and Tropical Medicine

Oxford
United Kingdom

Hamtandi Magloire Natama

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Burkina Faso

Athanase Somé

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Burkina Faso

Ousmane Traoré

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Burkina Faso

Toussaint Rouamba

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Burkina Faso

Duncan Bellamy

University of Oxford - The Jenner Institute Laboratories

Oxford
United Kingdom

Prisca Yameogo

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Burkina Faso

Daniel Valia

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Burkina Faso

Moubarak Tegneri

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Burkina Faso

Florence Ouedraogo

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Burkina Faso

Rachidatou Soma

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Burkina Faso

Seydou Sawadogo

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Burkina Faso

Faizatou Sorgho

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Burkina Faso

Karim Derra

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Burkina Faso

Eli Rouamba

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Burkina Faso

Benedict Orindi

Kenya Medical Research Institute (KEMRI)

Kenya

Fernando Ramos-Lopez

University of Oxford - Centre for Clinical Vaccinology and Tropical Medicine

Oxford
United Kingdom

Amy Flaxman

University of Oxford - The Jenner Institute ( email )

Old Road Campus Research Building Roosevelt Drive
Oxford, Oxfordshire OX3 7DQ
United Kingdom

Federica Cappuccini

University of Oxford - The Jenner Institute ( email )

Old Road Campus Research Building Roosevelt Drive
Oxford, Oxfordshire OX3 7DQ
United Kingdom

Reshma Kailath

University of Oxford - The Jenner Institute Laboratories

Oxford
United Kingdom

Sean C. Elias

University of Oxford - The Jenner Institute

Mansfield Road
Oxford, Oxfordshire OX1 4AU
United Kingdom

Ekta Mukhopadhyay

University of Oxford - The Jenner Institute Laboratories

Oxford
United Kingdom

Andres Noe

University of Oxford - The Jenner Institute Laboratories

Oxford
United Kingdom

Matthew Cairns

London School of Hygiene & Tropical Medicine

Keppel Street
London, WC1E 7HT
United Kingdom

Alison Lawrie

University of Oxford - Centre for Clinical Vaccinology and Tropical Medicine

Oxford
United Kingdom

Rachel Roberts

University of Oxford - Centre for Clinical Vaccinology and Tropical Medicine

Oxford
United Kingdom

Innocent Valéa

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Burkina Faso

Hermann Sorgho

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro

Burkina Faso

Nicola Williams

University of Oxford - Department of Primary Care Health Services

Oxford
United Kingdom

Gregory Glenn

Novavax

Gaithersburg, MD
United States

Louis Fries

Novavax

Gaithersburg, MD
United States

Jenny Reimer

Novavax AB

Uppsala
Sweden

Katie J. Ewer

University of Oxford - The Jenner Institute Laboratories

Oxford
United Kingdom

Umesh Shaligram

Serum Institute of India Private Ltd

Pune
India

Adrian V. S. Hill (Contact Author)

University of Oxford - The Jenner Institute

Old Road Campus Research Building Roosevelt Drive
Oxford, Oxfordshire OX3 7DQ
United Kingdom

University of Oxford - Wellcome Trust Centre for Human Genetics ( email )

Old Road Campus
Roosevelt Drive
Oxford, OX3 7FZ
United Kingdom

University of Oxford - Centre for Clinical Vaccinology and Tropical Medicine ( email )

Oxford
United Kingdom

Halidou Tinto

Institute de Recherche en Sciences de Santé (IRSS) - Clinical Research Unit of Nanoro ( email )

Burkina Faso

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