Background/Aim: Resurgence risk in immunization programs is driven less by vaccine efficacy than by heterogeneous coverage, immunity debt, and waning protection, where indiscriminate booster expansion may underperform targeted primary catch-up. We aimed to develop a decision-grade mathematical model to determine when booster versus primary vaccination maximizes population health impact under access inequities and supply constraints.
Methods: We constructed a harmonized country–age structured panel (2000–2024) for all Asia-Pacific countries with complete WHO–UNICEF WUENIC vaccine coverage time series (DTP3, MCV1/MCV2), IHME Global Burden of Disease incidence, mortality, and DALYs for vaccine-preventable outcomes, and World Bank World Development Indicators capturing demographic structure and health-system capacity. An age-structured SEIR–SIRS transmission model with two access strata (high- vs low-access populations) was calibrated using Bayesian particle Markov chain Monte Carlo with negative-binomial observation processes. Vaccine protection followed a bi-phasic waning structure (fast and slow decay components). We solved a constrained optimal-control problem allocating limited annual doses between primary-series expansion and booster vaccination to maximize discounted DALYs averted under supply and delivery-speed constraints. We derived the Coverage–Waning Interaction Index (CWI²), defined as the marginal DALYs averted per 100,000 booster doses relative to primary-series expansion, with uncertainty propagated from posterior simulations.
Results: Substantial within-country coverage inequities persisted during 2021–2024, markedly increasing modeled susceptibility despite stable national averages (p<0.001 versus pre-2020). Under immunity-debt recovery scenarios, optimal strategies favored primary-series expansion in most settings: reallocating 20% of booster supply to low-access primary catch-up reduced projected 2030 DALYs by 11.6% (95% UI 7.9–15.4) and decreased outbreak probability from 0.34 to 0.21 (Δ −0.13; 95% UI −0.19 to −0.06). In contrast, a subset of countries showed CWI²>1, where booster expansion yielded greater marginal benefit, averting an additional 4.1 DALYs per 100,000 doses (95% UI 2.2–6.3). A consistent policy tipping point emerged: once low-access primary coverage exceeded approximately 86% (range 82–90), booster strategies became dominant. These findings remained robust under probabilistic sensitivity analyses varying waning kinetics, rollout velocity, and supply ceilings by ±25%, with country policy rankings preserved in 92% of posterior simulations and outcome uncertainty intervals remaining non-overlapping. Model calibration achieved median posterior predictive error below 6%, with effective reproduction numbers declining proportionally to optimized dose reallocation across age strata.
Conclusions: This model identifies when booster vaccination outperforms primary coverage expansion under waning immunity and unequal access, providing dose-allocation thresholds that maximize DALYs averted under supply constraints across Asia-Pacific.