A single intranasal administration of AdCOVID protects against SARS-CoV-2 infection in the upper and lower respiratory tracts.

A single intranasal administration of AdCOVID protects against SARS-CoV-2 infection in the upper and lower respiratory tracts.
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DOI:
10.1080/21645515.2022.2127292
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发表时间:
2022-11-30
影响因子:
4.8
通讯作者:
--
中科院分区:
医学3区
文献类型:
--
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2019冠状病毒病(COVID-19)大流行表明,迫切需要有效的预防性疫苗接种,以防止严重急性呼吸系统综合征冠状病毒2(SARS-CoV-2)的传播。鼻内疫苗接种是预防COVID-19的一种有吸引力的方法,因为鼻粘膜是SARS-CoV-2最初进入和病毒复制的部位,然后吸入肺部。我们先前证明,单一鼻内施用编码SARS-CoV-2刺突蛋白受体结合结构域的候选5型腺病毒载体疫苗(AdCOVID)在气道粘膜和外周中诱导稳健的免疫,并且完全保护K18-hACE 2小鼠免受致死SARS-CoV-2攻击。在这里,我们表明,单次鼻内施用AdCOVID限制了K18-hACE 2小鼠鼻腔中的病毒复制。AdCOVID还诱导小鼠肺中的杀菌免疫,这反映在没有感染性病毒。最后,AdCOVID预防SARS-CoV-2诱导的小鼠肺部病理损伤。这些数据表明,AdCOVID不仅限制了呼吸道中的病毒复制,而且还预防了SARS-CoV-2感染后病毒诱导的炎症和免疫病理学。
The coronavirus disease 2019 (COVID-19) pandemic has illustrated the critical need for effective prophylactic vaccination to prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Intranasal vaccination is an attractive approach for preventing COVID-19 as the nasal mucosa is the site of initial SARS-CoV-2 entry and viral replication prior to aspiration into the lungs. We previously demonstrated that a single intranasal administration of a candidate adenovirus type 5-vectored vaccine encoding the receptor-binding domain of the SARS-CoV-2 spike protein (AdCOVID) induced robust immunity in both the airway mucosa and periphery, and completely protected K18-hACE2 mice from lethal SARS-CoV-2 challenge. Here we show that a single intranasal administration of AdCOVID limits viral replication in the nasal cavity of K18-hACE2 mice. AdCOVID also induces sterilizing immunity in the lungs of mice as reflected by the absence of infectious virus. Finally, AdCOVID prevents SARS-CoV-2 induced pathological damage in the lungs of mice. These data show that AdCOVID not only limits viral replication in the respiratory tract, but it also prevents virus-induced inflammation and immunopathology following SARS-CoV-2 infection.
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发表时间: 2021-02-04
期刊: The New England journal of medicine
影响因子: --
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Baden LR;El Sahly HM;Essink B;Kotloff K;Frey S;Novak R;Diemert D;Spector SA;Rouphael N;Creech CB;McGettigan J;Khetan S;Segall N;Solis J;Brosz A;Fierro C;Schwartz H;Neuzil K;Corey L;Gilbert P;Janes H;Follmann D;Marovich M;Mascola J;Polakowski L;Ledgerwood J;Graham BS;Bennett H;Pajon R;Knightly C;Leav B;Deng W;Zhou H;Han S;Ivarsson M;Miller J;Zaks T;COVE Study Group
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