Single-Dose Intranasal Administration of AdCOVID Elicits Systemic and Mucosal Immunity against SARS-CoV-2 and Fully Protects Mice from Lethal Challenge.

Single-Dose Intranasal Administration of AdCOVID Elicits Systemic and Mucosal Immunity against SARS-CoV-2 and Fully Protects Mice from Lethal Challenge.
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DOI:
10.3390/vaccines9080881
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发表时间:
2021-08-09
期刊:
影响因子:
7.8
通讯作者:
Roberts MS
Roberts MS
中科院分区:
医学3区
文献类型:
--
作者:
King RG;Silva-Sanchez A;Peel JN;Botta D;Dickson AM;Pinto AK;Meza-Perez S;Allie SR;Schultz MD;Liu M;Bradley JE;Qiu S;Yang G;Zhou F;Zumaquero E;Simpler TS;Mousseau B;Killian JT Jr;Dean B;Shang Q;Tipper JL;Risley CA;Harrod KS;Feng T;Lee Y;Shiberu B;Krishnan V;Peguillet I;Zhang J;Green TJ;Randall TD;Suschak JJ;Georges B;Brien JD;Lund FE;Roberts MS

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2019冠状病毒病(COVID-19)大流行凸显了有效预防接种疫苗的迫切需要,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的一种有吸引力的策略,因为鼻粘膜是SARS-CoV-2进入的一线屏障。目前的肌内疫苗引起全身免疫,但不一定是高水平的粘膜免疫。在这里,我们在近交系、远交系和转基因小鼠中测试了单次鼻内剂量的我们的候选5型腺病毒载体疫苗,该疫苗编码SARS-CoV-2刺突蛋白(AdCOVID)的受体结合结构域(RBD)。AdCOVID单次鼻内接种通过诱导呼吸道粘膜伊加、血清中和抗体以及具有Th 1样细胞因子表达谱的CD 4+和CD 8 + T细胞,引发了针对RBD的强烈和集中的免疫应答。一剂AdCOVID疫苗可使免疫力持续6个月以上。此外,单次鼻内给药完全保护K18-hACE 2小鼠免受致死性SARS-CoV-2攻击,防止体重减轻和死亡。这些数据表明,AdCOVID促进伴随的全身和粘膜免疫,代表了一种有希望的候选疫苗。
The coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need for effective prophylactic vaccination to prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Intranasal vaccination is an attractive strategy to prevent COVID-19 as the nasal mucosa represents the first-line barrier to SARS-CoV-2 entry. The current intramuscular vaccines elicit systemic immunity but not necessarily high-level mucosal immunity. Here, we tested a single intranasal dose of our candidate adenovirus type 5-vectored vaccine encoding the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein (AdCOVID) in inbred, outbred, and transgenic mice. A single intranasal vaccination with AdCOVID elicited a strong and focused immune response against RBD through the induction of mucosal IgA in the respiratory tract, serum neutralizing antibodies, and CD4+ and CD8+ T cells with a Th1-like cytokine expression profile. A single AdCOVID dose resulted in immunity that was sustained for over six months. Moreover, a single intranasal dose completely protected K18-hACE2 mice from lethal SARS-CoV-2 challenge, preventing weight loss and mortality. These data show that AdCOVID promotes concomitant systemic and mucosal immunity and represents a promising vaccine candidate.
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