Monovalent XBB.1.5 mRNA Vaccine Recalls a More Durable and Coordinated Antibody Response to SARS-CoV-2 Spike than the Bivalent WT/BA.5 mRNA Vaccine

In the fall of 2023, the monovalent XBB.1.5 mRNA vaccine for COVID-19 became available. However, the comparative magnitude, durability, and functionality of antibody responses induced by the XBB.1.5 vaccine compared with the 2022-2023 bivalent wildtype (WT) + Omicron BA.5 vaccine remains to be fully determined. In this study, we compared antibody profiles generated by these two vaccines in healthcare workers. We show that the monovalent XBB.1.5 vaccine induced higher magnitude binding, neutralizing, and Fc-gamma receptor (Fc{gamma}R) binding antibodies to the XBB.1.5 spike compared with the bivalent vaccine against the WT and BA.5 spikes, both at both peak immunogenicity and at 6 months post-vaccination. Moreover, antibody interaction architectures and correlations remained more robust at 6 months post-vaccination with the XBB.1.5 vaccine, whereas these correlations were largely lost at 6 months with the bivalent vaccine. Our results suggest that the XBB.1.5 vaccine led to a more durable and functionally coordinated antibody response compared to the bivalent vaccine.