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bioRxiv · 10.1101/2025.05.12.653567

Development of a cross-protective common cold coronavirus vaccine

Penaloza-MacMaster, P.·Dangi, T.·Li, S.
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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.

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Penaloza-MacMaster, P., Dangi, T., Li, S.. 2025-05-14. Development of a cross-protective common cold coronavirus vaccine. https://doi.org/10.1101/2025.05.12.653567

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