Development of a cross-protective common cold coronavirus vaccine.

Common cold coronaviruses, such as OC43 and HKU1, typically 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 coronavirus 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 a distant embecovirus, MHV-A59. These findings provide insights for the development of common cold coronavirus vaccines, demonstrating their potential to protect against various coronaviruses. IMPORTANCE Human coronaviruses like OC43 cause disease in vulnerable populations, yet no approved vaccines exist. We developed an mRNA vaccine targeting the OC43 spike protein that protects mice not only against homologous OC43 challenges but also against the distantly related embecovirus MHV-A59. These findings demonstrate the feasibility of a single vaccine conferring broad protection across multiple coronaviruses within the same subgenus, advancing strategies for pan-coronavirus vaccine development.