Halfmann Peter J, Patel Raj S, Loeffler Kathryn, Yasuhara Atsuhiro, Van De Velde Lee-Ann, Yang Jie E, Chervin Jordan, Troxell Chloe, Huang Min, Zheng Naiying, Wright Elizabeth R, Thomas Paul G, Wilson Patrick C, Kawaoka Yoshihiro, Kane Ravi S
Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA.
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
Nat Commun. 2025 Jan 7;16(1):462. doi: 10.1038/s41467-025-55824-y.
The continuing emergence of immune evasive SARS-CoV-2 variants and the previous SARS-CoV-1 outbreak collectively underscore the need for broadly protective sarbecovirus vaccines. Targeting the conserved S2 subunit of SARS-CoV-2 is a particularly promising approach to elicit broad protection. Here, we describe a nanoparticle vaccine displaying multiple copies of the SARS-CoV-1 S2 subunit. This vaccine alone, or as a cocktail with a SARS-CoV-2 S2 subunit vaccine, protects female transgenic K18-hACE2 mice from challenges with Omicron subvariant XBB as well as several sarbecoviruses identified as having pandemic potential including the bat sarbecovirus WIV1, BANAL-236, and a pangolin sarbecovirus. Challenge studies in female Fc-γ receptor knockout mice reveal that antibody-based cellular effector mechanisms play a role in protection elicited by these vaccines. These results demonstrate that our S2-based vaccines provide broad protection against clade 1 sarbecoviruses and offer insight into the mechanistic basis for protection.
免疫逃逸的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变异株持续出现，以及之前的SARS-CoV-1疫情，共同凸显了研发具有广泛保护作用的沙贝病毒疫苗的必要性。靶向SARS-CoV-2保守的S2亚基是一种特别有前景的引发广泛保护的方法。在此，我们描述了一种展示多个SARS-CoV-1 S2亚基拷贝的纳米颗粒疫苗。这种疫苗单独使用，或与SARS-CoV-2 S2亚基疫苗混合使用，可保护雌性转基因K18-hACE2小鼠免受奥密克戎变异株XBB以及几种被确定具有大流行潜力的沙贝病毒（包括蝙蝠沙贝病毒WIV1、BANAL-236和穿山甲沙贝病毒）的攻击。对雌性Fc-γ受体敲除小鼠的攻毒研究表明，基于抗体的细胞效应机制在这些疫苗引发的保护中发挥作用。这些结果表明，我们基于S2的疫苗可对第1进化枝沙贝病毒提供广泛保护，并为保护的机制基础提供了见解。
