Immunologic Evaluation of First and Second Doses of SARS-CoV-2 XBB.1.5 and the KP.2 Monovalent Booster Vaccines in Nursing Home Residents.

Publication date: Dec 14, 2025

Nursing home residents (NHRs) remain at high risk for severe outcomes following SARS-CoV-2 infection. Omicron descendants have dominated circulating strains, with XBB in 2023 and KP. 2 strain by mid-2024, leading to immune escape and increased transmissibility. We aimed to assess the immunogenicity of one versus two prior doses of the XBB. 1.5 vaccines and potential differences in the subsequent response to the KP. 2 booster. We conducted a longitudinal immunologic evaluation of 131 NHRs in Ohio and Rhode Island. Samples were collected 2-6 weeks after the first and second XBB. 1.5 vaccination doses, 60 days before KP. 2 vaccination, and 2-6 weeks after the KP. 2 booster. We measured anti-spike and neutralizing antibody titers to both XBB. 1.5 and KP. 2. NHRs who received two booster doses of the XBB. 1.5 vaccine developed higher peak anti-spike antibody levels (29,777 AU/mL) and neutralizing titers (7082) compared to those with only one dose (13,788 AU/mL and 1293, respectively). Over time, anti-spike antibody and neutralizing titers declined, but both remained higher in the two-dose group before receiving the KP. 2 vaccine. After vaccination with XBB. 1.5, neutralization against KP. 2 was significantly lower than against XBB. 1.5, suggesting reduced cross-reactivity and highlighting the potential for immune escape. However, KP. 2 vaccination markedly boosted neutralizing titers in all participants, regardless of their prior XBB. 1.5 dose history. NHRs who received a two-dose regimen of the XBB. 1.5 vaccine demonstrated stronger immune responses and higher pre-KP. 2 titers than those who received a single dose. However, the diminished cross-protective neutralization of KP. 2 highlights the variant’s immune evasiveness. The KP. 2 booster effectively elicited anti-KP. 2 levels, supporting the continued use of updated, variant-matched boosters to protect high-risk populations such as NHRs.

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