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.
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