Public health impact of catch-up vaccination or additional booster doses with pre-erythrocytic malaria vaccine...

The malaria vaccine R21/Matrix-M is recommended for young children in malaria-endemic regions. However, the small vaccine-eligible population and waning vaccine efficacy mean that routine vaccination is unlikely to prevent severe cases in older children who experience significant malaria burden. As R21/Matrix-M vaccination expands, targeting older age groups may be warranted, depending on funding.

Using a stochastic, individual-based Plasmodium falciparum malaria transmission model, we estimate the impact of (1) one-off catch-up campaigns with R21/Matrix-M to previously unvaccinated age groups between age 6 months and 14 years, and/or (2) extra boosters at 2, 5, and/or 10 years after the primary series in low, moderate, and high transmission settings. We assume that vaccine immunogenicity in older children is equivalent to that of the standard target age group, though clinical trials have shown lower immunogenicity in older children.

Catch-up campaigns in moderate-to-high transmission settings targeting younger children averted the most uncomplicated cases per 1000 additional doses (358 (95% credible interval (CI) 113-570) in children aged 6 months-2 years at 45% PfPR_2-10), compared with targeting older children. In low transmission settings, the impact was similar across age groups, with a slightly higher impact when targeting school-aged children (373 (95% CrI 240-518) in children aged 5-9 years at 5% PfPR_2-10). Across extra booster strategies, an extra booster 10 years post- primary series averted the most severe cases per 1000 additional doses at low transmission (12 (95% CrI 6-18) at 5% PfPR_2-10), but the least at high transmission (- 4 (95% CrI - 11-3) at 45% PfPR_2-10). Expanding the vaccine-eligible population in areas of moderate-to-high transmission often had higher incremental efficiency than routine age-based vaccination at low transmission. For example, an extra booster 5 years post-primary series averted 835 (95% CrI 605-1274) clinical cases per 1000 additional doses in a 45% PfPR_2-10 perennial setting versus 247 (95% CrI 177-345) clinical cases per 1000 doses with routine vaccination in a 5% PfPR_2-10 perennial setting. Sensitivity analyses assuming lower immunogenicity in older children modestly reduced the per-dose impact, but overall conclusions remained unchanged.

Catch-up campaigns or extra booster doses of R21/Matrix-M can provide benefits beyond routine administration, with the per-additional-dose value approaching that of routine vaccination, but this varies by transmission and seasonality setting. Further empirical studies, particularly on vaccine efficacy in older children, are warranted to inform policy guidance for malaria vaccination implementation.