Martinez David R, Schafer Alexandra, Gavitt Tyler D, Mallory Michael L, Lee Esther, Catanzaro Nicholas J, Chen Haiyan, Gully Kendra, Scobey Trevor, Korategere Pooja, Brown Alecia, Smith Lena, Parks Rob, Barr Maggie, Newman Amanda, Bowman Cindy, Powers John M, Mansouri Katayoun, Edwards Robert J, Baric Ralph S, Haynes Barton F, Saunders Kevin O
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.
bioRxiv. 2023 May 23:2023.05.22.540829. doi: 10.1101/2023.05.22.540829.
The emergence of three distinct highly pathogenic human coronaviruses - SARS-CoV in 2003, MERS-CoV in 2012, and SARS-CoV-2 in 2019 - underlines the need to develop broadly active vaccines against the and betacoronavirus subgenera. While SARS-CoV-2 vaccines are highly protective against severe COVID-19 disease, 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 and broad protection. Specifically, a 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. Moreover, the trivalent RBD scNP elicited serum neutralizing antibodies against SARS-CoV, MERS-CoV and SARS-CoV-2 BA.1 live viruses. Our findings show that a trivalent RBD nanoparticle vaccine displaying merbecovirus and sarbecovirus immunogens elicits immunity that broadly protects mice against disease. This study demonstrates proof-of-concept for a single pan-betacoronavirus vaccine to protect against three highly pathogenic human coronaviruses spanning two betacoronavirus subgenera.
三种不同的高致病性人类冠状病毒——2003年的SARS-CoV、2012年的MERS-CoV和2019年的SARS-CoV-2的出现，凸显了开发针对α和β冠状病毒亚属的广谱活性疫苗的必要性。虽然SARS-CoV-2疫苗对严重的COVID-19疾病具有高度保护作用，但它们不能预防其他沙贝病毒或中东呼吸综合征相关冠状病毒。在此，我们用一种三价分选酶偶联纳米颗粒（scNP）疫苗对小鼠进行免疫接种，该疫苗包含SARS-CoV-2、RsSHC014和MERS-CoV的受体结合域（RBD），可引发活病毒中和抗体反应和广泛保护。具体而言，单价SARS-CoV-2 RBD scNP疫苗仅能预防沙贝病毒攻击，而三价RBD scNP疫苗在高致病性和致死性小鼠模型中能预防中东呼吸综合征相关冠状病毒和沙贝病毒攻击。此外，三价RBD scNP引发了针对SARS-CoV、MERS-CoV和SARS-CoV-2 BA.1活病毒的血清中和抗体。我们的研究结果表明，展示中东呼吸综合征相关冠状病毒和沙贝病毒免疫原的三价RBD纳米颗粒疫苗可引发能广泛保护小鼠免受疾病侵害的免疫力。这项研究证明了单一泛β冠状病毒疫苗预防三种跨越两个β冠状病毒亚属的高致病性人类冠状病毒的概念验证。
