Development of a cross-protective common cold coronavirus vaccine

Abstract

Common cold coronaviruses, such as OC43 and HKU1, generally cause mild respiratory infections in healthy people. However, they can lead to severe illness in high-risk groups, including immunocompromised individuals and older adults. Currently, there is no clinically approved vaccine to prevent infection by common cold coronaviruses. Here, we developed an mRNA vaccine expressing a stabilized spike protein derived from OC43 and tested its efficacy in different challenge models in C57BL/6 mice. This novel OC43 vaccine elicited OC43-specific immune responses, as well as cross-reactive immune response against other embecoviruses, including HKU1 and mouse hepatitis virus (MHV-A59). Interestingly, this OC43 vaccine protected mice not only against a lethal OC43 infection, but also against MHV-A59, which is only 65% matched. Vaccine cross-protection appeared to be mechanistically mediated by non-neutralizing antibodies, but not by CD8 and CD4 T cells. These findings provide insights for the development of common cold coronavirus vaccines, demonstrating the potential for a single vaccine to target different members of a coronavirus subgenus.