Vaccine-mediated protection against merbecovirus and sarbecovirus challenge in mice.
Vaccine-mediated protection against merbecovirus and sarbecovirus challenge in mice.
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疫苗介导的针对小鼠 merbecovirus 和 sarbecovirus 攻击的保护。
DOI：
10.1101/2023.05.22.540829
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Bowman,C
中科院分区：
文献类型：
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作者：
Martinez,DavidR;Schafer,Alexandra;Gavitt,TylerD;Mallory,MichaelL;Lee,Esther;Catanzaro,NicholasJ;Chen,Haiyan;Gully,Kendra;Scobey,Trevor;Korategere,Pooja;Brown,Alecia;Smith,Lena;Parks,Rob;Barr,Maggie;Newman,Amanda;Bowman,C
三种高致病性人类冠状病毒的出现-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（MERS）-CoV和2019年的SARS-CoV-2-强调需要开发针对Merbecovirus和Sarbecovirus β冠状病毒亚属的广泛活性疫苗。虽然SARS-CoV-2疫苗可以预防严重的COVID-19，但它们不能预防其他Sarbecovirus或Merbecovirus。在这里，我们用含有SARS-CoV-2，RsSHC 014和MERS-CoV受体结合结构域（RBD）的三价分选酶缀合物纳米颗粒（scNP）疫苗接种小鼠，引发活病毒中和抗体应答。三价RBD scNP可诱导产生抗蝙蝠人畜共患病武汉病毒研究所1型（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疫苗仅保护抵抗Sarbecovirus攻击，而三价RBD scNP疫苗在高致病性和致死性小鼠模型中保护抵抗Merbecovirus和Sarbecovirus攻击。这项研究证明了单一泛Sarbecovirus/泛Merbecovirus疫苗的概念证明，该疫苗可预防跨越两个β冠状病毒亚属的三种高致病性人类冠状病毒。
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 theMerbecovirusandSarbecovirusbetacoronavirus 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 againstSarbecoviruschallenge, whereas the trivalent RBD scNP vaccine protected against bothMerbecovirusandSarbecoviruschallenge 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.