Department of Immunobiology, Yale School of Medicine, New Haven, CT 06510, USA; Yale Center for Infection and Immunity, Yale School of Medicine, New Haven, CT 06510, USA.
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Cell Rep. 2023 Oct 31;42(10):113248. doi: 10.1016/j.celrep.2023.113248. Epub 2023 Oct 18.
The emergence of three highly pathogenic human coronaviruses-severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, Middle Eastern respiratory syndrome (MERS)-CoV in 2012, and SARS-CoV-2 in 2019-underlines the need to develop broadly active vaccines against the Merbecovirus and Sarbecovirus betacoronavirus subgenera. While SARS-CoV-2 vaccines protect against severe COVID-19, they do not protect against other sarbecoviruses or merbecoviruses. Here, we vaccinate mice with a trivalent sortase-conjugate nanoparticle (scNP) vaccine containing the SARS-CoV-2, RsSHC014, and MERS-CoV receptor-binding domains (RBDs), which elicited live-virus neutralizing antibody responses. The trivalent RBD scNP elicited serum neutralizing antibodies against bat zoonotic Wuhan Institute of Virology-1 (WIV-1)-CoV, SARS-CoV, SARS-CoV-2 BA.1, SARS-CoV-2 XBB.1.5, and MERS-CoV live viruses. The monovalent SARS-CoV-2 RBD scNP vaccine only protected against Sarbecovirus challenge, whereas the trivalent RBD scNP vaccine protected against both Merbecovirus and Sarbecovirus challenge in highly pathogenic and lethal mouse models. This study demonstrates proof of concept for a single pan-sarbecovirus/pan-merbecovirus vaccine that protects against three highly pathogenic human coronaviruses spanning two betacoronavirus subgenera.
三种高致病性人类冠状病毒——2003 年的严重急性呼吸综合征冠状病毒（SARS-CoV）、2012 年的中东呼吸综合征冠状病毒（MERS-CoV）和 2019 年的 SARS-CoV-2——的出现，凸显了开发针对 Merbecovirus 和 Sarbecovirus betacoronavirus 亚属的广泛有效的疫苗的必要性。虽然 SARS-CoV-2 疫苗能预防严重的 COVID-19，但它们不能预防其他 sarbecoviruses 或 merbecoviruses。在这里，我们用包含 SARS-CoV-2、RsSHC014 和 MERS-CoV 受体结合域（RBD）的三价 sortase 缀合纳米颗粒（scNP）疫苗对小鼠进行免疫接种，该疫苗能引发活病毒中和抗体反应。三价 RBD scNP 能诱导针对蝙蝠源性武汉病毒研究所-1（WIV-1）-CoV、SARS-CoV、SARS-CoV-2 BA.1、SARS-CoV-2 XBB.1.5 和 MERS-CoV 活病毒的血清中和抗体。单价 SARS-CoV-2 RBD scNP 疫苗只能预防 Sarbecovirus 攻击，而三价 RBD scNP 疫苗能在高致病性和致死性的小鼠模型中预防 Merbecovirus 和 Sarbecovirus 的攻击。这项研究证明了一种单泛 Sarbecovirus/泛 Merbecovirus 疫苗的概念验证，该疫苗能预防跨越两个 betacoronavirus 亚属的三种高致病性人类冠状病毒。
