Humoral immunity to current variants of SARS-CoV-2 in exposed adults, September 2023 to September 2024.

SARS-CoV-2 evolves variants that evade population immunity. Monitoring group-level immunity is critical for assessing population susceptibility to newly circulating variants and updateability of imprinted immunity after exposure. We established a closely monitored cohort of 58 fully vaccinated adults in Berlin, Germany. Of these, 49 had at least one previous Omicron infection. In September 2023 and again in September 2024, we analyzed neutralizing antibody responses using full-virus plaque reduction neutralization tests against seven SARS-CoV-2 variants: B.1, BA.2, BA.5, EG.5.1, JN.1, KP.3.1.1, and XEC. Vaccination and exposure histories were traced using medical records, RT-PCR testing of any episode of respiratory tract infection, and serological testing for subclinical infections. Infecting variants were determined by sequencing or from unequivocal variant circulation at the time of positive testing. Titers from September 2023 included responses to both then-current and future variants. Over the study period, 13 subjects received monovalent XBB.1.5 vaccine. Thirty-four had one, and five more than one SARS-CoV-2 infection. None of the subjects was exposed to the most recent variant, XEC. Neutralization titers against all tested variants increased over time. Highest fold increases were seen against KP.3.1.1 and XEC. Reactivity profiles differed by exposure histories reflecting the most recent variant contact. Exposure to new variants leads to relative updates in population-level neutralizing antibody activity. Despite these updates, absolute group-level neutralization activity was low in September 2024 due to low titer levels against currently circulating variants KP.3.1.1 and XEC. Ongoing monitoring is needed to assess the need for further vaccine updates.IMPORTANCEAs new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants continue to emerge, understanding how population immunity evolves is essential to guide vaccine updates and public health strategies. Our study follows a group of fully vaccinated adults for 1 year (September 2023 to September 2024) to track how infection and vaccination affect the ability to neutralize new viral variants. Despite the continued emergence of immune escape variants, the results show that infection with recent variants helps to "update" immunity at the group level, even against newer variants such as KP.3.1.1 and XEC, although titers to new variants were low, confirming the existence of immune imprinting. These findings suggest that exposure to new variants adapts the immune system over time. This provides valuable insight into how populations build resilience against SARS-CoV-2 and whether updated vaccines are needed.