Assessing the best time interval between doses in a two-dose vaccination regimen to reduce the number of deaths in an ongoing epidemic of SARS-CoV-2

The SARS-CoV-2 pandemic is a major concern all over the world and, as vaccines became available at the end of 2020, optimal vaccination strategies were subjected to intense investigation. Considering their critical role in reducing disease burden, the increasing demand outpacing production, and that most currently approved vaccines follow a two-dose regimen, the cost-effectiveness of delaying the second dose to increment the coverage of the population receiving the first dose is often debated. Finding the best solution is complex due to the trade-off between vaccinating more people with lower level of protection and guaranteeing higher protection to a fewer number of individuals. Here we present a novel extended age-structured SEIR mathematical model that includes a two-dose vaccination schedule with a between-doses delay modelled through delay differential equations and linear optimization of vaccination rates. By maintaining the minimum stock of vaccines under a given production rate, we evaluate the dose interval that minimizes the number of deaths. We found that the best strategy depends on an interplay between the vaccine production rate and the relative efficacy of the first dose. In the scenario of low first-dose efficacy, it is always better to vaccinate the second dose as soon as possible, while for high first-dose efficacy, the best strategy of time window depends on the production rate and also on second-dose efficacy provided by each type of vaccine. We also found that the rate of spread of the infection does not affect significantly the thresholds of the best window, but is an important factor in the absolute number of total deaths. These conclusions point to the need to carefully take into account both vaccine characteristics and roll-out speed to optimize the outcome of vaccination strategies.Author summary: Science responded quickly to the COVID-19 pandemic, and many vaccines became available to contain the disease severity around the world. With a wide variety of vaccines, decision makers need to choose the best time interval between the doses of vaccines to apply in a population, given the epidemic situation and the efficacy of the different vaccines. In this work, we studied the best interval between doses of three different vaccines against COVID-19 using a mathematical model. For the modeling, we took into account individuals of different age groups, as they respond differently to vaccination depending on their age, and also the efficacy of vaccines after one dose and after complete vaccination (2 doses). We evaluated which interval between doses leads to fewer deaths. We found that if the efficacy of the first dose is low compared to complete vaccination, then vaccinating the second dose at a short interval leads to fewer deaths. On the other hand, if the efficacy of the first dose is high enough, the best strategy depends on vaccine availability. If vaccine supply is large, giving the second dose earlier is better. However, the postponement of the second dose results in fewer deaths in a situation of vaccine shortage.