Immunogenicity of the Monovalent Omicron XBB.1.5-Adapted BNT162b2 COVID-19 Vaccine Against XBB.1.5, BA.2.86, and JN.1 Sublineages: A Phase 2/3 Trial <strong> </strong>

We report neutralization titer data against contemporary SARS-CoV-2 sublineages from an ongoing, open-label, phase 2/3 trial of a single 30-&mu;g dose of monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine. Healthy participants had previously received &ge;3 doses of a US-authorized mRNA vaccine, with the most recent being a bivalent Omicron BA.4/BA.5-adapted vaccine administered &ge;150 days before study vaccination. In this analysis, Omicron XBB.1.5, BA.2.86, and JN.1 serum neutralizing titers were assessed at baseline and 1 month after vaccination in a subset of &ge;18-year-olds (N = 40) with evidence of previous SARS-CoV-2 infection. Immunogenicity was also evaluated in a demographically matched group of participants who received bivalent BA.4/BA.5-adapted BNT162b2 in another study (ClinicalTrials.gov Identifier: NCT05472038). The XBB.1.5-adapted BNT162b2 vaccine elicited higher XBB.1.5, BA.2.86, and JN.1 neutralizing titers than those elicited by bivalent BA.4/BA.5-adapted BNT162b2. Overall geometric mean fold rises in neutralizing titers from baseline to 1 month after vaccination were higher among participants who received XBB.1.5-adapted BNT162b2 than those who received bivalent BA.4/BA.5-adapted BNT162b2 for XBB.1.5 (7.6 vs 5.6), slightly higher for JN.1 (3.9 vs 3.5), and similar for BA.2.86 (4.8 vs 4.9). ClinicalTrials.gov Identifier: NCT05997290.