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Abstract BackgroundThe emergence of antimalarial drug resistance poses a major threat to effective malaria treatment and control. This study aims to inform policymakers and vaccine developers on the potential of an effective malaria vaccine in reducing drug-resistant infections. MethodsA compartmental model estimating cases, drug-resistant cases, and deaths averted from 2021 to 2030 with a vaccine againstPlasmodium falciparuminfection administered yearly to 1-year-olds in 42 African countries. Three vaccine efficacy (VE) scenarios and one scenario of rapidly increasing drug resistance are modeled. ResultsWhen VE is constant at 40% for 4 years and then drops to 0%, 235.7 (Uncertainty Interval [UI] 187.8–305.9) cases per 1000 children, 0.6 (UI 0.4–1.0) resistant cases per 1000, and 0.6 (UI 0.5–0.9) deaths per 1000 are averted. When VE begins at 80% and drops 20 percentage points each year, 313.9 (UI 249.8–406.6) cases per 1000, 0.9 (UI 0.6–1.3) resistant cases per 1000, and 0.9 (UI 0.6–1.2) deaths per 1000 are averted. When VE remains 40% for 10 years, 384.7 (UI 311.7–496.5) cases per 1000, 1.0 (0.7–1.6) resistant cases per 1000, and 1.1 (UI 0.8–1.5) deaths per 1000 are averted. Assuming an effective vaccine and an increase in current levels of drug resistance to 80% by 2030, 10.4 (UI 7.3–15.8) resistant cases per 1000 children are averted. ConclusionsWidespread deployment of a malaria vaccine could substantially reduce health burden in Africa. Maintaining VE longer may be more impactful than a higher initial VE that falls rapidly.