Longitudinal antibody titers measured after COVID-19 mRNA vaccination can identify individuals at risk for subsequent infection

Abstract

A key issue in the post–COVID-19 pandemic era is the ongoing administration of COVID-19 vaccines. Repeated vaccination is essential for preparing against currently circulating and newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. However, optimizing vaccination strategies is crucial to efficiently manage medical resources and establish an effective vaccination framework. Therefore, a strategy to identify poor responders with lower sustained antibody titers would be beneficial because these individuals should be considered high priority for revaccination. We investigated longitudinal antibody titer data in a cohort of 2526 people in Fukushima, Japan, collected between April 2021 and November 2022. Using mathematical modeling and machine learning, we stratified the time-course patterns of antibody titers after two primary doses and one booster dose of COVID-19 messenger RNA vaccines. We identified three populations, which we refer to as the durable, the vulnerable, and the rapid-decliner populations, and approximately half of the participants remained in the same population after the booster dose. The rapid-decliner population experienced earlier infections than the others. Furthermore, when comparing spike protein–specific immunoglobulin G (IgG) titers, spike protein–specific IgA titers, and SARS-CoV-2–specific T cell responses between participants who experienced subsequent infections after booster vaccination and those who did not, we found that spike protein–specific IgA titers were lower during the early stage after booster vaccination in participants who went on to become infected with SARS-CoV-2. This approach could be used to inform policy decisions on vaccine distribution to maximize population-level immunity both in future pandemics and in the post–COVID-19 pandemic era.