Cao Huibi, Mai Juntao, Zhou Zhichang, Li Zhijie, Duan Rongqi, Watt Jacqueline, Chen Ziyan, Bandara Ranmal Avinash, Li Ming, Ahn Sang Kyun, Poon Betty, Christie-Holmes Natasha, Gray-Owen Scott D, Banerjee Arinjay, Mossman Karen, Kozak Rob, Mubareka Samira, Rini James M, Hu Jim, Liu Jun
Translational Medicine Program, Hospital for Sick Children Research Institute, Toronto, ON, Canada.
Department of Molecular Genetics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Cell Biosci. 2021 Dec 8;11(1):202. doi: 10.1186/s13578-021-00723-0.
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.
持续的新冠疫情已在全球导致1.85亿例确诊病例和400多万人死亡。几种新冠疫苗已获批用于人类紧急使用,并在许多国家投入使用。然而,所有获批的疫苗均通过肌肉注射给药,这可能无法预防上呼吸道感染或病毒传播。
在此,我们描述了一种基于辅助依赖型腺病毒(HD-Ad)载体的新型鼻内递送新冠疫苗。该疫苗(HD-Ad_RBD)产生严重急性呼吸综合征冠状病毒2(SARS-CoV-2)刺突蛋白受体结合域(RBD)的可溶性分泌形式,并且我们证明它能诱导强大的黏膜和全身免疫。此外,使用初免-加强方案对K18-hACE2小鼠进行HD-Ad_RBD鼻内免疫,可对上呼吸道提供完全保护,使其免受SARS-CoV-2感染。
我们的方法为构建针对SARS-CoV-2及其新出现变体的高效疫苗提供了一个强大的平台。