Dangi Tanushree, Li Shiyi, Penaloza-MacMaster Pablo
Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
bioRxiv. 2025 May 14:2025.05.12.653567. doi: 10.1101/2025.05.12.653567.
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.
常见的感冒冠状病毒，如OC43和HKU1，通常在健康人群中引起轻度呼吸道感染。然而，它们可导致高危人群，包括免疫功能低下者和老年人出现严重疾病。目前，尚无临床批准的疫苗可预防常见感冒冠状病毒感染。在此，我们开发了一种表达源自OC43的稳定刺突蛋白的mRNA疫苗，并在C57BL/6小鼠的不同攻毒模型中测试了其疗效。这种新型OC43疫苗引发了OC43特异性免疫反应，以及针对其他包膜病毒的交叉反应性免疫反应，包括HKU1和小鼠肝炎病毒（MHV-A59）。有趣的是，这种OC43疫苗不仅保护小鼠免受致死性OC43感染，还能抵御匹配度仅为65%的MHV-A59。疫苗的交叉保护作用似乎是由非中和抗体介导的，而非CD8和CD4 T细胞。这些发现为感冒冠状病毒疫苗的开发提供了见解，证明了单一疫苗针对冠状病毒一个亚属的不同成员的潜力。
