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

Cell & Bioscience

Natasha Christie-Holmes¹  Betty Poon¹  Karen Mossman²  Scott D. Gray-Owen³  Zhichang Zhou³  Ming Li³  Sang Kyun Ahn³  Jun Liu³  Juntao Mai³  Jacqueline Watt³  Zhijie Li³  James M. Rini⁴  Rob Kozak⁵  Samira Mubareka⁵  Rongqi Duan⁶  Huibi Cao⁶  Jim Hu⁷  Ziyan Chen⁷  Ranmal Avinash Bandara⁷  Arinjay Banerjee⁸ 

[1] Combined Containment Level 3 Unit, Faculty of Medicine, University of Toronto, Toronto, ON, Canada;Department of Medicine Institute for Infectious Disease Research, McMaster Immunology Research Center, McMaster University, Hamilton, ON, Canada;Department of Molecular Genetics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada;Department of Molecular Genetics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada;Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada;Sunnybrook Heath Sciences Centre, Toronto, ON, Canada;Translational Medicine Program, Hospital for Sick Children Research Institute, Toronto, ON, Canada;Translational Medicine Program, Hospital for Sick Children Research Institute, Toronto, ON, Canada;Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada;Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK, Canada;Department of Veterinary Microbiology, University of Saskatchewan, Saskatoon, SK, Canada;Department of Biology, University of Waterloo, Waterloo, ON, Canada;

关键词: COVID-19;    HD-Ad;    Nasal delivery;    SARS-CoV2;    Vaccine;   

DOI  :  10.1186/s13578-021-00723-0

来源: Springer

【 摘 要 】

BackgroundThe 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.ResultsHere, 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.ConclusionOur approaches provide a powerful platform for constructing highly effective vaccines targeting SARS-CoV-2 and its emerging variants.

【 授权许可】

CC BY