Neutralization of SARS-CoV-2 Omicron XBB.1.5 and JN.1 variants after COVID-19 booster-vaccination and infection

SARS-CoV-2 Omicron lineages continue to emerge and evolve into new sublineages, causing infection waves throughout 2022 and 2023, which has been attributed to immune escape. We examined neutralizing antibody responses to the recently emerged SARS-CoV-2 JN.1 variant in comparison to ancestral D614G and Omicron BA.1, BA.2, BA.5, and XBB.1.5 variants. We tested 79 human sera from cohorts with different combinations of vaccinations and infections, including 23 individuals who had been repeatedly exposed to Omicron. Individuals with a monovalent XBB.1.5 vaccine booster or XBB.1.5 breakthrough infection had robust antibody levels against all variants tested; however, JN.1 evaded antibodies in individuals after single Omicron BA.1, BA.2 or BA.5 breakthrough infections. Moreover, in the non-vaccinated cohort, serum antibodies demonstrated almost no cross-neutralization activities against D614G, XBB.1.5 and JN.1. after infections with earlier Omicron variants. These findings show that SARS-CoV-2-immunity is heterogeneous, depending on different combinations of vaccinations and infections, and emphasize the importance of considering different immune-backgrounds when evaluating novel variants.