Schiavone, Carmine (2025) Scale-Up from Individuals to Populations: Process-Aware Optimization of Antibody Durability and Boosting. [Tesi di dottorato]

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Abstract

Vaccination averts millions of deaths, but protection wanes and varies by variant, age, and immune competence. This thesis links within‑host immunodynamics to dosing policy to minimize vulnerability windows—the time antibody titers fall below efficacy‑relevant thresholds. We develop a mechanistic model of antigen presentation, T follicular helper mediated germinal‑center selection and affinity maturation, plasma‑cell (short‑lived and long‑lived) generation, and neutralizing IgG kinetics, calibrated to longitudinal datasets. We then perform schedule optimization over primary dose spacing and booster timing to balance near‑term coverage against maturation, stratified by immune status (healthy, mildly, highly immuno-compromised). At the individual level, early post‑dose titers inform compact parameter sets that predict peak magnitude and durability, enabling phenotype‑aware recommendations. Finally, individual parameter distributions are propagated through between‑host transmission models to compare phenotype‑aware boosting with coarse health‑factor rules, preferentially targeting weak responders while conserving doses in strong responders.

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