Intranasal HD-Ad vaccine protects the upper and lower respiratory tracts of hACE2 mice against SARS-CoV-2.

Intranasal HD-Ad vaccine protects the upper and lower respiratory tracts of hACE2 mice against SARS-CoV-2.
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DOI:
10.1186/s13578-021-00723-0
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发表时间:
2021-12-08
期刊:
影响因子:
7.5
通讯作者:
Liu J
Liu J
中科院分区:
生物学2区
文献类型:
--
作者:
Cao H;Mai J;Zhou Z;Li Z;Duan R;Watt J;Chen Z;Bandara RA;Li M;Ahn SK;Poon B;Christie-Holmes N;Gray-Owen SD;Banerjee A;Mossman K;Kozak R;Mubareka S;Rini JM;Hu J;Liu J

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持续的COVID-19大流行已导致全球1. 85亿例记录病例和超过400万例死亡。几种COVID-19疫苗已被批准用于人类紧急使用,并正在许多国家使用。然而,所有批准的疫苗都是通过肌肉注射给药,这可能无法预防上呼吸道感染或病毒传播。在这里,我们描述了一种基于辅助依赖性腺病毒(HD-Ad)载体的新型鼻内递送COVID-19疫苗。该疫苗(HD-Ad_RBD)产生SARS-CoV-2刺突蛋白的受体结合结构域(RBD)的可溶性分泌形式,并且我们显示其诱导了稳健的粘膜和全身免疫。此外,使用初免-加强方案用HD-Ad_RBD鼻内免疫K18-hACE 2小鼠,导致完全保护上呼吸道免受SARS-CoV-2感染。我们的方法为构建针对SARS-CoV-2及其新变种的高效疫苗提供了一个强大的平台。在线版本包含补充材料,可通过10.1186/s13578-021-00723-0获得。
The ongoing COVID-19 pandemic has resulted in 185 million recorded cases and over 4 million deaths worldwide. Several COVID-19 vaccines have been approved for emergency use in humans and are being used in many countries. However, all the approved vaccines are administered by intramuscular injection and this may not prevent upper airway infection or viral transmission. Here, we describe a novel, intranasally delivered COVID-19 vaccine based on a helper-dependent adenoviral (HD-Ad) vector. The vaccine (HD-Ad_RBD) produces a soluble secreted form of the receptor binding domain (RBD) of the SARS-CoV-2 spike protein and we show it induced robust mucosal and systemic immunity. Moreover, intranasal immunization of K18-hACE2 mice with HD-Ad_RBD using a prime-boost regimen, resulted in complete protection of the upper respiratory tract against SARS-CoV-2 infection. Our approaches provide a powerful platform for constructing highly effective vaccines targeting SARS-CoV-2 and its emerging variants. The online version contains supplementary material available at 10.1186/s13578-021-00723-0.
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