Durability of Humoral Immune Response Following Booster Vaccination in Older Adults

Abstract

Booster vaccination has become a central strategy for restoring humoral immunity in older adults, whose primary vaccine responses are consistently blunted by immunosenescence, yet how long that restored protection actually persists in this population remains incompletely characterized. This article synthesizes the literature on the durability of antibody responses following booster vaccination in older adults, drawing primarily on the large real-world COVID-19 booster cohorts from Israel and Qatar alongside the longer-established influenza and pneumococcal vaccine durability literature. We trace the biological basis of age-related decline in germinal center function and long-lived plasma cell generation, the foundational trial and national booster evidence showing that a booster dose sharply restores antibody titers and clinical protection, and the subsequent kinetic studies showing that this restored protection itself wanes, often within months, with the extent of waning shaped by frailty, comorbidity, and prior infection history. We also examine the emerging evidence that hybrid immunity, combining infection and vaccination, confers greater durability than vaccination alone, complicating population-level durability estimates. Read together, the evidence supports a consistent restoration-then-waning pattern across vaccine platforms and cohorts, while leaving frailty-stratified, multi-year durability data and individualized revaccination intervals as an open research and policy agenda.