Deviation from the recommended schedule: optimal dosing interval for a two-dose vaccination programme.

Optimizing vaccination impact during an emerging disease becomes crucial when vaccine supply is limited, and robust protection requires multiple doses. Facing this challenge during the early stages of the COVID-19 vaccine deployment, a pivotal policy question arose: whether to administer a single dose to a larger proportion of the population by deferring the second dose, or to prioritize stronger protection for a smaller subset of the population with the established dosing interval from clinical trials. Using a delay-differential model and considering waning immunity and distribution capacity, we compared these strategies. We found that the efficacy of the first dose significantly influences the impact of delaying the second dose. Even for a relatively low efficacy of the first dose, a delayed strategy may outperform vaccination with the recommended dosing interval in reducing short-term hospitalizations and deaths despite increase in infections. The optimal delay, however, depends on the specific outcome measured and timelines within which the vaccination strategy is evaluated. We found transition lines for the relative reduction of infection, hospitalization and death below which vaccination with the recommended schedule is the preferred strategy. In a realistic parameter space, our results highlight scenarios in which the conclusions of previous studies are invalid.