Immunological heterogeneity informs estimation of the durability of COVID-19 vaccine protection

Deciphering the properties of vaccines against coronavirus disease 2019 (COVID-19) is essential to predict the future course of the pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, current uncertainties about COVID-19 vaccine immunity raise the question of how much time will be needed to estimate these properties, in particular the durability of vaccine protection. Here we designed a simulation study, based on empirically validated epidemiological models of SARS-CoV-2 transmission, to predict the impact of a breadth of vaccines with different mean duration (range: 2–5 years) and heterogeneity (coefficient of variation range: 50–100%) of protection against infection. We then assessed how confidently the duration of protection could be estimated under a range of epidemiological scenarios in the year following the start of mass immunization. We found that lower population mean and higher inter-individual variability facilitated estimation of the duration of vaccine protection. Across the vaccines tested, high waning and high heterogeneity permitted complete identification of the duration of protection; in contrast, low waning and low heterogeneity allowed only estimation of the fraction of vaccinees with rapid loss of immunity. These findings suggest that key aspects of COVID-19 vaccine immunity can be estimated with limited epidemiological data. More generally, they highlight that immunological heterogeneity can sensitively determine the impact of COVID-19 vaccines and, it is likely, of other vaccines.