The public health impact and cost-effectiveness of the R21/Matrix-M malaria vaccine: a mathematical modelling study

Lancet Infect Dis. 2024 May;24(5):465-475. doi: 10.1016/S1473-3099(23)00816-2. Epub 2024 Feb 8.


Background: The R21/Matrix-M vaccine has demonstrated high efficacy against Plasmodium falciparum clinical malaria in children in sub-Saharan Africa. Using trial data, we aimed to estimate the public health impact and cost-effectiveness of vaccine introduction across sub-Saharan Africa.

Methods: We fitted a semi-mechanistic model of the relationship between anti-circumsporozoite protein antibody titres and vaccine efficacy to data from 3 years of follow-up in the phase 2b trial of R21/Matrix-M in Nanoro, Burkina Faso. We validated the model by comparing predicted vaccine efficacy to that observed over 12-18 months in the phase 3 trial. Integrating this framework within a mathematical transmission model, we estimated the cases, malaria deaths, and disability-adjusted life-years (DALYs) averted and cost-effectiveness over a 15-year time horizon across a range of transmission settings in sub-Saharan Africa. Cost-effectiveness was estimated incorporating the cost of vaccine introduction (dose, consumables, and delivery) relative to existing interventions at baseline. We report estimates at a median of 20% parasite prevalence in children aged 2-10 years (PfPR2-10) and ranges from 3% to 65% PfPR2-10.

Findings: Anti-circumsporozoite protein antibody titres were found to satisfy the criteria for a surrogate of protection for vaccine efficacy against clinical malaria. Age-based implementation of a four-dose regimen of R21/Matrix-M vaccine was estimated to avert 181 825 (range 38 815-333 491) clinical cases per 100 000 fully vaccinated children in perennial settings and 202 017 (29 868-405 702) clinical cases per 100 000 fully vaccinated children in seasonal settings. Similar estimates were obtained for seasonal or hybrid implementation. Under an assumed vaccine dose price of US$3, the incremental cost per clinical case averted was $7 (range 4-48) in perennial settings and $6 (3-63) in seasonal settings and the incremental cost per DALY averted was $34 (29-139) in perennial settings and $30 (22-172) in seasonal settings, with lower cost-effectiveness ratios in settings with higher PfPR2-10.

Interpretation: Introduction of the R21/Matrix-M malaria vaccine could have a substantial public health benefit across sub-Saharan Africa.

Funding: The Wellcome Trust, the Bill & Melinda Gates Foundation, the UK Medical Research Council, the European and Developing Countries Clinical Trials Partnership 2 and 3, the NIHR Oxford Biomedical Research Centre, and the Serum Institute of India, Open Philanthropy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Protozoan / blood
  • Burkina Faso / epidemiology
  • Child
  • Child, Preschool
  • Cost-Benefit Analysis*
  • Female
  • Humans
  • Infant
  • Malaria Vaccines* / administration & dosage
  • Malaria Vaccines* / economics
  • Malaria Vaccines* / immunology
  • Malaria, Falciparum* / economics
  • Malaria, Falciparum* / epidemiology
  • Malaria, Falciparum* / prevention & control
  • Male
  • Models, Theoretical*
  • Plasmodium falciparum / immunology
  • Protozoan Proteins / immunology
  • Public Health* / economics
  • Vaccine Efficacy


  • Malaria Vaccines
  • Protozoan Proteins
  • Antibodies, Protozoan
  • circumsporozoite protein, Protozoan