Evaluation of COVID-19 vaccination strategies with a delayed second dose (preprint)

ABSTRACT

COVID-19 vaccines currently approved in the United States require two doses, administered three to four weeks apart. Constraints in vaccine supply and distribution capacity, together with the rise of COVID-19 cases and hospitalizations, have sparked a policy debate on whether to vaccinate more individuals with the first dose of available vaccines and delay the second dose, or to continue with the recommended two-dose series as tested in clinical trials. We developed an agent-based model of COVID-19 transmission to compare the impact of these two vaccination strategies, while varying the temporal waning of vaccine efficacy against disease following the first dose, vaccine efficacy against infection, and the level of pre-existing immunity in the population. Our results show that for Moderna vaccines with 80% efficacy following the first dose, a delay of 9-12 weeks could enhance the program effectiveness and prevent additional infections, hospitalizations, and deaths, compared to a 4-week interval between the doses. However, for Pfizer-BioNTech vaccines with demonstrated efficacy of 52% after the first dose, there was no clear advantage for delaying the second dose beyond the 3-week tested schedule, unless the efficacy of the first dose did not wane over time. Our findings underscore the importance of quantifying the durability of vaccine-induced protection after the first dose as well as vaccine efficacy against infection in order to determine the optimal time interval between the two doses.