Antibody responses to SARS-CoV-2 variants LP.8.1, LF.7.1, NB.1.8.1, XFG, and BA.3.2 following KP.2 monovalent mRNA vaccination.

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in antigenically distinct variants that challenge vaccine-induced immunity. The KP.2 monovalent mRNA vaccine was deployed in 2024 to address immune escape by emerging SARS-CoV-2 subvariants. We assessed neutralizing antibody responses in 56 adults with varied exposure histories following KP.2 vaccination against emerging variants including LP.8.1, LF.7.1, NB.1.8.1, XFG, and BA.3.2. While KP.2 vaccination enhanced neutralization against homologous variants, substantial reductions in neutralizing activity were observed against emerging Omicron variants across all exposure groups. Exposure history showed some influence on neutralization breadth, with self-reported vaccination-only participants exhibiting better cross-neutralization compared to individuals with hybrid immunity. Antigenic cartography revealed substantial antigenic distances between KP.2 and emerging variants, highlighting significant immune escape potential that threatens vaccine protection.IMPORTANCESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, producing variants that escape vaccine-induced immunity. The current work shows that KP.2 monovalent vaccination provides limited protection against antigenically distant Omicron variants (LP.8.1, LF.7.1, NB.1.8.1, XFG and BA.3.2). These findings highlight the ongoing challenge of maintaining vaccine effectiveness against evolving SARS-CoV-2 variants and argue for continuous updating of vaccines.