Neutralizing antibody durability and SARS-CoV-2 infection in older adults six months after XBB-containing vaccine booster

The persistence of XBB-containing vaccine-induced immunity against evolving SARS-CoV-2 variants remains uncertain, particularly in older adults, who are at increased risk of severe outcomes and may experience more rapid immune decline. We previously reported neutralizing antibody (nAb) responses 21 days after a single booster dose of trivalent XBB.1.5 (Tri‑XBB.1.5), bivalent Omicron XBB (Bi‑Omi‑XBB), or tetravalent XBB.1 (Tetra‑XBB.1) vaccines in a cohort of 90 older adults aged >65 years. In this six-month longitudinal follow-up analysis of the same cohort, we assessed nAb durability and SARS-CoV-2 infections to extend our earlier findings. Six months post-vaccination, the nAb titers decreased over time, with 2.5‒4.6-fold reductions in the geometric mean titer against the variants KP.3.1.1 and XEC; however, the nAb titer remained detectable in most participants. The Tri‑XBB.1.5 vaccine exhibited marginally better antibody persistence than the Bi‑Omi‑XBB and Tetra‑XBB.1 vaccines did, suggesting potential formulation-dependent differences in long-term immunogenicity. Twenty-seven participants experienced SARS-CoV-2 infection, including 11 (12.2%) confirmed by rapid antigen testing and 16 (17.8%) classified as probably based on serological evidence, with relatively frequent infections in bivalent and tetravalent recipients. Lower nAb titers on day 21 were linked to early infections, whereas late infections reflected antibody waning. Infections transiently increased nAb levels, but the elevated titers were not sustained. These findings highlight the importance of updating booster formulations and improving vaccine designs to address emerging immune-evasive variants.