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

Huibi Cao; Juntao Mai; Zhichang Zhou; Zhijie Li; Rongqi Duan; Jacqueline Watt; Ziyan Chen; Ranmal Avinash Bandara; Ming Li; Sang Kyun Ahn; Betty Poon; Natasha Christie-Holmes; Scott D Gray-Owen; Arinjay Banerjee; Karen Mossman; Rob Kozak; Samira Mubareka; James M Rini; Jim Hu; Jun Liu

doi:10.1186/s13578-021-00723-0

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

Cell Biosci. 2021 Dec 8;11(1):202. doi: 10.1186/s13578-021-00723-0.

Authors

Huibi Cao^#¹, Juntao Mai^#², Zhichang Zhou^#², Zhijie Li², Rongqi Duan¹, Jacqueline Watt², Ziyan Chen^{1

3}, Ranmal Avinash Bandara^{1

3}, Ming Li², Sang Kyun Ahn², Betty Poon⁴, Natasha Christie-Holmes⁴, Scott D Gray-Owen², Arinjay Banerjee^{5

6

7}, Karen Mossman⁸, Rob Kozak⁹, Samira Mubareka⁹, James M Rini^{10

11}, Jim Hu^{12

13}, Jun Liu¹⁴

Affiliations

¹ Translational Medicine Program, Hospital for Sick Children Research Institute, Toronto, ON, Canada.
² Department of Molecular Genetics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
³ Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
⁴ Combined Containment Level 3 Unit, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
⁵ Vaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK, Canada.
⁶ Department of Veterinary Microbiology, University of Saskatchewan, Saskatoon, SK, Canada.
⁷ Department of Biology, University of Waterloo, Waterloo, ON, Canada.
⁸ Department of Medicine Institute for Infectious Disease Research, McMaster Immunology Research Center, McMaster University, Hamilton, ON, Canada.
⁹ Sunnybrook Heath Sciences Centre, Toronto, ON, Canada.
¹⁰ Department of Molecular Genetics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada. james.rini@utoronto.ca.
¹¹ Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada. james.rini@utoronto.ca.
¹² Translational Medicine Program, Hospital for Sick Children Research Institute, Toronto, ON, Canada. jim.hu@sickkids.ca.
¹³ Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada. jim.hu@sickkids.ca.
¹⁴ Department of Molecular Genetics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada. jun.liu@utoronto.ca.

^# Contributed equally.

Abstract

Background: 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.

Results: 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.

Conclusion: Our approaches provide a powerful platform for constructing highly effective vaccines targeting SARS-CoV-2 and its emerging variants.

Keywords: COVID-19; HD-Ad; Nasal delivery; SARS-CoV2; Vaccine.

Abstract

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