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

被引：17

作者：

Cao, Huibi ^{[1
]}

Mai, Juntao ^{[2
]}

Zhou, Zhichang ^{[2
]}

Li, Zhijie ^{[2
]}

Duan, Rongqi ^{[1
]}

Watt, Jacqueline ^{[2
]}

Chen, Ziyan ^{[1
,3
]}

Bandara, Ranmal Avinash ^{[1
,3
]}

Li, Ming ^{[2
]}

Ahn, Sang Kyun ^{[2
]}

Poon, Betty ^{[4
]}

Christie-Holmes, Natasha ^{[4
]}

Gray-Owen, Scott D. ^{[2
]}

Banerjee, Arinjay ^{[5
,6
,7
]}

Mossman, Karen ^{[8
]}

Kozak, Rob ^{[9
]}

Mubareka, Samira ^{[9
]}

Rini, James M. ^{[2
,10
]}

Hu, Jim ^{[1
,3
]}

Liu, Jun ^{[2
]}

机构：

[1] Hosp Sick Children, Translat Med Program, Res Inst, Toronto, ON, Canada

[2] Univ Toronto, Fac Med, Dept Mol Genet, Toronto, ON, Canada

[3] Univ Toronto, Fac Med, Dept Lab Med & Pathobiol, Toronto, ON, Canada

[4] Univ Toronto, Fac Med, Combined Containment Level Unit 3, Toronto, ON, Canada

[5] Univ Saskatchewan, Vaccine & Infect Dis Org, Saskatoon, SK, Canada

[6] Univ Saskatchewan, Dept Vet Microbiol, Saskatoon, SK, Canada

[7] Univ Waterloo, Dept Biol, Waterloo, ON, Canada

[8] McMaster Univ, McMaster Immunol Res Ctr, Dept Med, Inst Infect Dis Res, Hamilton, ON, Canada

[9] Sunnybrook Heath Sci Ctr, Toronto, ON, Canada

[10] Univ Toronto, Fac Med, Dept Biochem, Toronto, ON, Canada

来源：

CELL AND BIOSCIENCE | 2021年 / 11卷 / 01期

基金：

加拿大健康研究院;

关键词：

COVID-19; HD-Ad; Nasal delivery; SARS-CoV2; Vaccine; DEPENDENT ADENOVIRAL VECTORS; RECEPTOR-BINDING DOMAIN; TRANSGENE EXPRESSION; GENE-TRANSFER; IMMUNITY; DIFFERENTIATION; INFECTION; DELIVERY;

D O I：

10.1186/s13578-021-00723-0

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：13

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