Multivalent S2-based vaccines provide broad protection against SARS-CoV-2 variants of concern and pangolin coronaviruses.
Multivalent S2-based vaccines provide broad protection against SARS-CoV-2 variants of concern and pangolin coronaviruses.
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DOI：
10.1016/j.ebiom.2022.104341
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发表时间：
2022-12
期刊：
影响因子：
11.1
通讯作者：
Kane, Ravi S.
中科院分区：
文献类型：
--
作者：
Halfmann, Peter J.;Frey, Steven J.;Loef, Kathryn;Kuroda, Makoto;Maemura, Tadashi;Armbrust, Tammy;Yang, Jie E.;Hou, Yixuan J.;Baric, Ralph;Wright, Elizabeth R.;Kawaoka, Yoshihiro;Kane, Ravi S.
COVID-19疫情继续在全球造成发病率及死亡率。大多数获批的COVID-19疫苗产生的中和抗体反应主要针对SARS-CoV-2刺突蛋白的高度可变受体结合域（RBD）。SARS-CoV-2“令人担忧的变异体”在这一领域获得了突变，使它们能够逃避疫苗诱导的体液免疫。最近提高SARS-CoV-2以外的保护范围的方法需要使用来自不同肉瘤病毒的RBD抗原的混合物。因此，开发一种保护性免疫应答靶向S蛋白更保守区域的疫苗可能是有益的。在这里，我们已经开发了一种疫苗的基础上保守的S2亚基的S蛋白，并优化佐剂和免疫方案在叙利亚仓鼠和BALB/c小鼠。我们已经确定了疫苗对SARS-CoV-2变异体和其他冠状病毒的有效性。用基于S2的构建体免疫引发了广泛的交叉反应性IgG抗体应答，其不仅识别SARS-CoV-2变体的刺突蛋白，还识别SARS-CoV-1和四种地方性人类冠状病毒的刺突蛋白。重要的是，免疫接种降低了SARS-CoV-2变异体B.1.351（beta）、B.1.617.2（delta）和BA.1（omicron）以及穿山甲冠状病毒攻击的接种动物呼吸道组织中的病毒滴度。这些结果表明，基于S2的构建体可以引发广泛的交叉反应性抗体应答，导致有限的病毒复制，从而为设计引发针对冠状病毒的广泛保护的疫苗提供了框架。、主席基金，以及。
The COVID-19 pandemic continues to cause morbidity and mortality worldwide. Most approved COVID-19 vaccines generate a neutralizing antibody response that primarily targets the highly variable receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein. SARS-CoV-2 “variants of concern” have acquired mutations in this domain allowing them to evade vaccine-induced humoral immunity. Recent approaches to improve the breadth of protection beyond SARS-CoV-2 have required the use of mixtures of RBD antigens from different sarbecoviruses. It may therefore be beneficial to develop a vaccine in which the protective immune response targets a more conserved region of the S protein. Here we have developed a vaccine based on the conserved S2 subunit of the S protein and optimized the adjuvant and immunization regimen in Syrian hamsters and BALB/c mice. We have characterized the efficacy of the vaccine against SARS-CoV-2 variants and other coronaviruses. Immunization with S2-based constructs elicited a broadly cross-reactive IgG antibody response that recognized the spike proteins of not only SARS-CoV-2 variants, but also SARS-CoV-1, and the four endemic human coronaviruses. Importantly, immunization reduced virus titers in respiratory tissues in vaccinated animals challenged with SARS-CoV-2 variants B.1.351 (beta), B.1.617.2 (delta), and BA.1 (omicron) as well as a pangolin coronavirus. These results suggest that S2-based constructs can elicit a broadly cross-reactive antibody response resulting in limited virus replication, thus providing a framework for designing vaccines that elicit broad protection against coronaviruses. , , Chair Fund, and .
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影响因子：
8.8
作者：
Halfmann PJ;Kuroda M;Armbrust T;Accola M;Valdez R;Kowalski-Dobson T;Rehrauer W;Gordon A;Kawaoka Y
通讯作者：
Kawaoka Y
影响因子：
30.5
作者：
He, Wan-ting;Musharrafieh, Rami;Song, Ge;Dueker, Katharina;Tse, Longping V.;Martinez, David R.;Schafer, Alexandra;Callaghan, Sean;Yong, Peter;Beutler, Nathan;Torres, Jonathan L.;Volk, Reid M.;Zhou, Panpan;Yuan, Meng;Liu, Hejun;Anzanello, Fabio;Capozzola, Tazio;Parren, Mara;Garcia, Elijah;Rawlings, Stephen A.;Smith, Davey M.;Wilson, Ian A.;Safonova, Yana;Ward, Andrew B.;Rogers, Thomas F.;Baric, Ralph S.;Gralinski, Lisa E.;Burton, Dennis R.;Andrabi, Raiees
通讯作者：
Andrabi, Raiees
影响因子：
10
作者：
Castro A;Carreño JM;Duehr J;Krammer F;Kane RS
通讯作者：
Kane RS
影响因子：
64.5
作者：
Hoffmann M;Krüger N;Schulz S;Cossmann A;Rocha C;Kempf A;Nehlmeier I;Graichen L;Moldenhauer AS;Winkler MS;Lier M;Dopfer-Jablonka A;Jäck HM;Behrens GMN;Pöhlmann S
通讯作者：
Pöhlmann S
影响因子：
56.9
作者：
Hsieh, Ching-Lin;Goldsmith, Jory A.;McLellan, Jason S.
通讯作者：
McLellan, Jason S.