Humoral Immunity after mRNA Omicron JN.1 Vaccination

In late June 2024, the European Medicines Agency (EMA) recommended market authorization for a monovalent COVID-19 mRNA-vaccine based on JN.1 spike. We assessed immune responses in n=42 health-care workers (median age 47 years, interquartile range, IQR 19{middle dot}5 years, 48% male), who in August 2024 were vaccinated with 30 g of the updated mRNA omicron JN.1 vaccine (bretovameran, BioNTech/Pfizer, Mainz, Germany). Humoral immune responses were analyzed directly prior to and 13 days after vaccination. The omicron JN.1 vaccination resulted in a significant 1{middle dot}2-fold increase of anti-S IgG and 1{middle dot}2-fold increase of omicron anti-S IgG (p<0{middle dot}0001). To assess plasma neutralisation capacity, we employed a pseudovirus particle (pp) neutralisation assay including S proteins of seven SARS-CoV-2 lineages. Baseline response rates were 100% for XBB.1.5pp, 90% for JN.1pp and KP.2pp, 82% for KP.2.3pp, 92% for KP.3pp, and 72% for LB.1pp. Before JN.1 vaccination, particles bearing KP sublineage S proteins were slightly less efficiently neutralised compared with JN.1pp (median change, 1{middle dot}2-fold to 2{middle dot}6-fold), while LB.1pp neutralisation was 3-fold reduced, indicating antibody evasion. After vaccination, the response rates increased significantly for all pseudoviruses except XBB.1.5pp and KP.3pp. Thus, we observed a significant increase in neutralisation of JN.1pp, KP.2pp, KP.2.3pp, and LB.1pp, showing a median change of 2.2-fold, 3.8-fold, 3.3-fold, and 4.9-fold, respectively. In summary, bretovameran increased anti-S IgG and strengthened neutralising responses against circulating SARS-CoV-2-variants, except for KP.3. We wish to point out that our study population exhibited high pre-vaccination omicron-related hybrid immunity and may not be representative of other populations. Our data supports the notion that the new mRNA vaccine against omicron JN.1 most likely increases protection against hospitalization and post-COVID sequelae caused by most current variants.