2025/08/27 by Anass Abbad, Brian Lerman, Jordan Ehrenhaus +15 · 1 voice
Medicine · #COVID-19 Clinical Research Studies #Heparin-Induced Thrombocytopenia and Thrombosis #SARS-CoV-2 and COVID-19 Research
paper · pdf · doi:10.1101/2025.08.24.25333689
openalex publication_date 2025/08/27 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22
ABSTRACT 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, dramatic 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. Overall, our data suggest that KP.2 boosting predominantly enhances cross-reactive responses imprinted by previously encountered spike antigens, with limited adaptation to antigenically drifted variants. IMPORTANCE 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.