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The Public Health Impact and Cost-Effectiveness of the R21/Matrix-M Malaria Vaccine: A Mathematical Modelling Study

26 Pages Posted: 11 Oct 2023

See all articles by Nora Schmit

Nora Schmit

Imperial College London - MRC Centre for Global Infectious Disease Analysis

Hillary M. Topazian

Imperial College London - MRC Centre for Global Infectious Disease Analysis

Magloire H. Natama

Institute de Recherche en Sciences de Santé (IRSS)

Duncan Bellamy

University of Oxford

Ousmane Traoré

Institute de Recherche en Sciences de Santé (IRSS)

Athasana M. Some

Institute de Recherche en Sciences de Santé (IRSS)

Toussaint Rouamba

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

Marc C. Tahita

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

Massa Achille Bonko

Institute de Recherche en Sciences de Santé (IRSS)

Aboubakary Sourabié

Institute de Recherche en Sciences de Santé (IRSS)

Hermann Sorgho

Institute de Recherche en Sciences de Santé (IRSS)

Lisa Stockdale

University of Oxford

Samuel Provstgaard-Morys

University of Oxford - The Jenner Institute

Jeremy Aboagye

University of Oxford - The Jenner Institute

Danielle Woods

University of Oxford - The Jenner Institute

Katerina Rapi

University of Oxford - The Jenner Institute

Mehreen S. Datoo

University of Oxford - Centre for Clinical Vaccinology and Tropical Medicine

Fernando Ramos Lopez

University of Oxford

Giovanni Charles

Imperial College London - MRC Centre for Global Infectious Disease Analysis

Kelly McCain

Imperial College London

Jean-Bosco Ouédraogo

Institute de Recherche en Sciences de Santé (IRSS)

Mainga Hamaluba

University of Oxford - KEMRI-Coast Centre for Geographical Medicine and Research

Ally Olotu

Ifakara Health Institute

Alassane Dicko

University of Sciences, Technique and Technologies of Bamako (USTTB) - Malaria Research and Training Centre

Halidou Tinto

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

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

Katie Ewer

GSK plc; University of Oxford - The Jenner Institute

Azra Ghani

Imperial College London - MRC Centre for Global Infectious Disease Analysis; Imperial College London - NIHR Health Protection Research Unit for Modelling and Health Economics

Peter Winskill

Imperial College London - MRC Centre for Global Infectious Disease Analysis

More...

Abstract

Background: The R21/Matrix-M vaccine which induces anti-circumsporozoite protein (CSP) antibodies against P. falciparum has demonstrated high efficacy against clinical malaria in Phase 2 and 3 trials in children in sub-Saharan Africa (SSA). We used data from these trials to estimate the public health impact and cost-effectiveness of vaccine introduction across SSA.

Methods: We fitted a semi-mechanistic model of the relationship between anti-CSP antibody titres and vaccine efficacy to immunogenicity and clinical data over 3 years of follow-up from the Phase 2b trial undertaken in Nanoro, Burkina Faso. We validated the model by comparing predicted vaccine efficacy to that observed over 12-18 months of follow-up in five Phase 3 trial sites. Integrating this model within a mathematical transmission model, we estimated the cases, malaria deaths and DALYs averted, and cost-effectiveness across a range of transmission settings in SSA over a 15-year time horizon. We report estimates at a median of 20% parasite prevalence in children aged 2-10 years (PfPR2-10) and ranges representing 3% and 65% PfPR2-10.

Findings: Anti-CSP antibody titres were found to satisfy the criteria for a surrogate of protection for vaccine efficacy against clinical malaria. Introduction of a four-dose regimen of R21/Matrix-M vaccine under age-based implementation is estimated to avert 190,602 [range 42,236 to 330,866] clinical cases and 632 [range 268 to 633] malaria deaths for every 100,000 fully vaccinated children in perennial settings, and 210,616 [range 32,428 to 398,620] clinical cases and 663 [range 216 to 719] malaria deaths per 100,000 fully vaccinated children in seasonal settings. Similar estimates were obtained for seasonal or hybrid implementation. R21/Matrix-M was more cost-effective in settings with higher parasite prevalence. Under an assumed dose price of US$3 we estimated a median incremental cost-effectiveness ratio compared with current interventions of $7 [range $42, $4] and $6 [range $56, $3] per clinical case averted and $36 [range $126, $34] and $33 [range $158, $27] per DALY averted in perennial and seasonal settings, respectively.

Interpretation: Introduction of the R21/Matrix-M malaria vaccine could have a substantial public health benefit and is cost-effective compared to other malaria interventions and other childhood vaccines.

Funding: This work was supported by a joint investigator award to ACG and Prof Katharina Hauck from the Wellcome Trust [reference 220900/Z/20/Z]. PW acknowledges support from the Bill and Melinda Gates Foundation [INV-043624]. ACG, NS, HT, and PW acknowledge funding from the MRC Centre for Global Infectious Disease Analysis (reference MR/R015600/1), jointly funded by the UK Medical Research Council (MRC) and the UK Foreign, Commonwealth & Development Office (FCDO), under the MRC/FCDO Concordat agreement and which is also part of the EDCTP2 programme supported by the European Union. The Phase 2 trial was mainly funded by a European and Developing Countries Clinical Trials Partnership (EDCTP2) grant (funded in turn by the European Union) to the Multi-Stage Malaria Vaccine Consortium (grant agreement RIA2016V-1649), with additional support from the Wellcome Trust through Translation Award 205981/Z/17/Z, and from the UK National Institute for Health Research to the Oxford Biomedical Research Centre's Vaccines for Emerging and Endemic Diseases theme. Vaccine manufacture and supply was supported and undertaken by the Serum Institute of India, and the Matrix-M adjuvant was provided by Novavax. The Phase 3 trial was mainly funded by the Serum Institute of India Pvt Ltd. (SIIPL) with additional funding to some trial sites from Open Philanthropy

Declaration of Interest: AVSH and KJE are named as co-inventors on patent applications related to R21. The other authors declare no competing interests.

Ethical Approval: The Phase 2 trial was approved by the Comité d'Ethique pour la Recherche en Santé, Burkina Faso (reference number 2019-01-012), and the national regulatory authority, Agence National de Régulation Pharmaceutique, Burkina Faso (reference number 5005420193EC0000). Ethical approval was also granted in the UK by the Oxford Tropical Research Ethics Committee (reference number 19-19). Ethical approval for the secondary data analysis was granted by Imperial College London (ICREC reference number 6278940). The Phase 3 trial was approved by the following ethics committees: L’Université des Sciences, des Techniques et des Technologies de Bamako, Faculté de Médecine et d’Odonto-Stomatologie, Faculté de Pharmacie/BP 1805, Bamako, Mali; Comité d’Ethique pour la Recherche en Santé (CERS), Ministère de l’Enseignement Superieur, de la Recherche Scientifique et de l’Innovation, Ministère de la Santé, 09 BP 7009 Ouagadougou 09, Burkina Faso; Kenya Medical Research Institute, Scientific and ethics review unit, PO Box 54840 00200, Nairobi, Kenya; National Institute for Medical Research (NIMR), 3 Barack Obama Drive, P. O. Box 9653, 11101 Dar es Salaam, Tanzania. Ethical approval was also granted in the UK by the Oxford Tropical Research Ethics Committee (reference number 8-21).

Suggested Citation

Schmit, Nora and Topazian, Hillary M. and Natama, Magloire H. and Bellamy, Duncan and Traoré, Ousmane and Some, Athasana M. and Rouamba, Toussaint and Tahita, Marc C. and Bonko, Massa Achille and Sourabié, Aboubakary and Sorgho, Hermann and Stockdale, Lisa and Provstgaard-Morys, Samuel and Aboagye, Jeremy and Woods, Danielle and Rapi, Katerina and Datoo, Mehreen S. and Lopez, Fernando Ramos and Charles, Giovanni and McCain, Kelly and Ouédraogo, Jean-Bosco and Hamaluba, Mainga and Olotu, Ally and Dicko, Alassane and Tinto, Halidou and Hill, Adrian V. S. and Ewer, Katie and Ghani, Azra and Winskill, Peter, The Public Health Impact and Cost-Effectiveness of the R21/Matrix-M Malaria Vaccine: A Mathematical Modelling Study. Available at SSRN: https://ssrn.com/abstract=4597985 or http://dx.doi.org/10.2139/ssrn.4597985

Nora Schmit (Contact Author)

Imperial College London - MRC Centre for Global Infectious Disease Analysis ( email )

Hillary M. Topazian

Imperial College London - MRC Centre for Global Infectious Disease Analysis ( email )

Magloire H. Natama

Institute de Recherche en Sciences de Santé (IRSS) ( email )

Duncan Bellamy

University of Oxford ( email )

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Ousmane Traoré

Institute de Recherche en Sciences de Santé (IRSS) ( email )

Athasana M. Some

Institute de Recherche en Sciences de Santé (IRSS) ( email )

Toussaint Rouamba

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

Burkina Faso

Marc C. Tahita

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

Massa Achille Bonko

Institute de Recherche en Sciences de Santé (IRSS) ( email )

Aboubakary Sourabié

Institute de Recherche en Sciences de Santé (IRSS) ( email )

Hermann Sorgho

Institute de Recherche en Sciences de Santé (IRSS) ( email )

Lisa Stockdale

University of Oxford ( email )

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Samuel Provstgaard-Morys

University of Oxford - The Jenner Institute ( email )

Jeremy Aboagye

University of Oxford - The Jenner Institute ( email )

Danielle Woods

University of Oxford - The Jenner Institute ( email )

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

Katerina Rapi

University of Oxford - The Jenner Institute ( email )

Mehreen S. Datoo

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

Fernando Ramos Lopez

University of Oxford ( email )

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Giovanni Charles

Imperial College London - MRC Centre for Global Infectious Disease Analysis ( email )

Kelly McCain

Imperial College London ( email )

Jean-Bosco Ouédraogo

Institute de Recherche en Sciences de Santé (IRSS) ( email )

Mainga Hamaluba

University of Oxford - KEMRI-Coast Centre for Geographical Medicine and Research ( email )

Ally Olotu

Ifakara Health Institute ( email )

Tanzania

Alassane Dicko

University of Sciences, Technique and Technologies of Bamako (USTTB) - Malaria Research and Training Centre ( email )

Halidou Tinto

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

Adrian V. S. Hill

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

Katie Ewer

GSK plc ( email )

Brentford
United Kingdom

University of Oxford - The Jenner Institute ( email )

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

Azra Ghani

Imperial College London - MRC Centre for Global Infectious Disease Analysis ( email )

South Kensington Campus
Exhibition Road
London, Greater London SW7 2AZ
United Kingdom

Imperial College London - NIHR Health Protection Research Unit for Modelling and Health Economics ( email )

London
United Kingdom

Peter Winskill

Imperial College London - MRC Centre for Global Infectious Disease Analysis ( email )

London
United Kingdom