Public health impact of catch-up vaccination or additional booster doses with pre-erythrocytic malaria vaccine R21/Matrix-M: a modelling study

Background The pre-erythrocytic malaria vaccine R21/Matrix-M is recommended for young children, who often bear the highest burden, in malaria endemic regions. However, the small proportion of the vaccine-eligible population and waning vaccine efficacy means that routine administration is unlikely to prevent all severe cases in older children who still experience significant disease burden and mortality. Given the anticipated wide availability of R21/Matrix-M, vaccinating older age groups may be warranted. Methods and Findings Using a stochastic, individual-based transmission model of P. falciparum malaria, we estimate the impact of (1) a one-off catch-up campaign expanding the R21/Matrix-M vaccine-eligible population to a range of previously unvaccinated age groups between 6 months and 14 years, and (2) extra booster doses at 2, 5 and/or 10 years after the primary series in a range of transmission settings. We assume that the vaccine efficacy in older children is the same as in the standard target age group of 5–17-month-olds. Prioritising expansion of the vaccine-eligible population through either catch-up campaigns to children under 5 years or via extra booster doses in areas of moderate or high transmission is predicted to prevent more clinical and severe cases per dose in nearly all scenarios than prioritising routine vaccination in areas of low transmission. For example, boosters 5 years post primary series averted 9 (95% CrI 5-13) severe cases per 1000 doses in a perennial setting with 45% PfPR2-10 versus 5 (95% CrI 2-8) severe cases per 1000 doses in children receiving routine vaccination at 5% PfPR2-10. Conclusion Additional doses of R21/Matrix-M delivered through catch-up campaigns or via extra booster doses can provide additional benefits to routine administration, but the value varies by transmission and seasonality setting. Further empirical studies, especially on vaccine efficacy in older children, are warranted to inform future policy guidance for malaria vaccination implementation.