Longitudinal humoral and memory B-cell responses to repeated SARS-CoV-2 vaccination in long-term care facilities residents

BACKGROUND: Long-term care facility (LTCF) residents represent one of the populations most vulnerable to SARS-CoV-2 infection and have experienced repeated vaccination and natural viral exposure since the beginning of the COVID-19 pandemic. The long-term dynamics of humoral and cellular immunity in this population remain incompletely characterized. In this multicenter longitudinal study, SARS-CoV-2-specific antibody responses were monitored in LTCF residents over 12 months. A total of 388 residents from LTCF across five Italian regions were enrolled and stratified according to receipt of the SARS-CoV-2 XBB.1.5 mRNA booster during the 2023-2024 vaccination campaign. In a subgroup of residents, peripheral B-cell phenotypes and Spike-specific memory B cells were characterized by flow cytometry and compared with those of younger healthcare workers vaccinated with the same formulation. RESULTS: Anti-Spike IgG titers peaked in residents who received the XBB.1.5 booster and subsequently declined over time, consistent with contraction of vaccine-induced humoral responses. In contrast, individuals who did not receive the booster maintained lower but stable antibody levels. Anti-nucleocapsid seroconversion and clinically diagnosed intercurrent infections occurred at broadly comparable observed rates in boosted and non-boosted residents, suggesting a comparable incidence of SARS-CoV-2 infection during follow-up. Regarding B-cell-mediated immunity, LTCF residents exhibited age-associated remodeling of the B-cell compartment, with reduced total B-cell frequencies but preserved antigen-experienced memory populations. Despite declining circulating antibodies, Spike-specific memory B-cell frequencies remained stable. A late increase in anti-Spike titers coincided with rising anti-nucleocapsid seropositivity, suggesting reactivation of immune memory following natural viral exposure. CONCLUSIONS: These findings indicate that repeated vaccination and natural exposure generate durable immunological memory in LTCF residents. In highly exposed populations, immune maintenance may increasingly rely on reactivation of memory responses rather than persistently high antibody titers.