Characterization and immunogenicity of nanoparticle vaccines displaying embecovirus spike proteins.

Endemic human coronaviruses OC43 and HKU1 cause widespread respiratory infections and can be associated with severe illness in immunocompromised and elderly individuals. Frequent adaptive evolution in the spike proteins of these embecoviruses and the potential for zoonotic transmission from a large animal reservoir necessitates the characterization of the immunogenic landscape of the spike proteins of embecoviruses. Here, we constructed nanoparticle vaccines displaying the spike antigens from OC43, HKU1 A, or HKU1 B, as well as a bivalent formulation incorporating spike antigens from OC43 and HKU1 A. Immunization of mice elicited spike-specific IgG antibody responses, with endpoint titers demonstrating cross-reactivity among clade-matched viruses. Notably, the bivalent formulation elicited antibody responses comparable to those of monovalent vaccines against matched antigens. These findings inform future design of vaccines against human-infecting embecoviruses and could serve as an important step toward a universal vaccine against common cold causing coronaviruses.