Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters.

Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters.
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DOI:
10.1038/s41591-020-1070-6
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发表时间:
2020-11
期刊:
影响因子:
82.9
通讯作者:
Barouch DH
Barouch DH
中科院分区:
医学1区
文献类型:
--
作者:
Tostanoski LH;Wegmann F;Martinot AJ;Loos C;McMahan K;Mercado NB;Yu J;Chan CN;Bondoc S;Starke CE;Nekorchuk M;Busman-Sahay K;Piedra-Mora C;Wrijil LM;Ducat S;Custers J;Atyeo C;Fischinger S;Burke JS;Feldman J;Hauser BM;Caradonna TM;Bondzie EA;Dagotto G;Gebre MS;Jacob-Dolan C;Lin Z;Mahrokhian SH;Nampanya F;Nityanandam R;Pessaint L;Porto M;Ali V;Benetiene D;Tevi K;Andersen H;Lewis MG;Schmidt AG;Lauffenburger DA;Alter G;Estes JD;Schuitemaker H;Zahn R;Barouch DH

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人类冠状病毒病2019(新冠肺炎)在临床上通常是一种轻微的疾病,但一些人会发展成严重的肺炎、呼吸衰竭和死亡。关于严重急性呼吸综合征冠状病毒2(SARS-CoV-2)在仓鼠和非人灵长类动物中感染的研究通常报道了轻微的临床疾病,临床前的SARS-CoV-2疫苗研究表明非人灵长类动物上呼吸道和下呼吸道的病毒复制减少。在这里,我们表明,大剂量鼻腔感染SARS-CoV-2会导致严重的临床疾病,包括组织中高水平的病毒复制、广泛的肺炎、体重减轻和动物亚群的死亡。表达稳定的SARS-CoV-2刺突蛋白的26型腺病毒载体疫苗一次免疫可诱导结合和中和抗体反应,并对SARS-CoV-2诱导的体重减轻、肺炎和死亡率具有保护作用。这些数据表明疫苗对SARS-CoV-2临床疾病具有保护作用。该模型将被证明对SARS-CoV-2疫苗、治疗和发病机制的临床前研究有用。表达稳定的SARS-CoV-2刺突蛋白的腺病毒载体疫苗一次免疫可诱导对SARS-CoV-2诱导的金黄地鼠体重减轻、肺炎和死亡的保护作用。
Coronavirus disease 2019 (COVID-19) in humans is often a clinically mild illness, but some individuals develop severe pneumonia, respiratory failure and death. Studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hamsters and nonhuman primates have generally reported mild clinical disease, and preclinical SARS-CoV-2 vaccine studies have demonstrated reduction of viral replication in the upper and lower respiratory tracts in nonhuman primates. Here we show that high-dose intranasal SARS-CoV-2 infection in hamsters results in severe clinical disease, including high levels of virus replication in tissues, extensive pneumonia, weight loss and mortality in a subset of animals. A single immunization with an adenovirus serotype 26 vector-based vaccine expressing a stabilized SARS-CoV-2 spike protein elicited binding and neutralizing antibody responses and protected against SARS-CoV-2-induced weight loss, pneumonia and mortality. These data demonstrate vaccine protection against SARS-CoV-2 clinical disease. This model should prove useful for preclinical studies of SARS-CoV-2 vaccines, therapeutics and pathogenesis. A single immunization with an adenovirus vector-based vaccine expressing a stabilized SARS-CoV-2 spike protein induces protection against SARS-CoV-2-induced weight loss, pneumonia and mortality in hamsters.
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