EBioMedicine (Jan 2022)
Nasal prevention of SARS-CoV-2 infection by intranasal influenza-based boost vaccination in mouse models
- Runhong Zhou,
- Pui Wang,
- Yik-Chun Wong,
- Haoran Xu,
- Siu-Ying Lau,
- Li Liu,
- Bobo Wing-Yee Mok,
- Qiaoli Peng,
- Na Liu,
- Kin-Fai Woo,
- Shaofeng Deng,
- Rachel Chun-Yee Tam,
- Haode Huang,
- Anna Jinxia Zhang,
- Dongyan Zhou,
- Biao Zhou,
- Chun-Yin Chan,
- Zhenglong Du,
- Dawei Yang,
- Ka-Kit Au,
- Kwok-Yung Yuen,
- Honglin Chen,
- Zhiwei Chen
Affiliations
- Runhong Zhou
- AIDS Institute, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China
- Pui Wang
- Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; State Key Laboratory for Emerging Infectious Diseases, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China
- Yik-Chun Wong
- AIDS Institute, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China
- Haoran Xu
- AIDS Institute, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China
- Siu-Ying Lau
- Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; State Key Laboratory for Emerging Infectious Diseases, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China
- Li Liu
- AIDS Institute, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; State Key Laboratory for Emerging Infectious Diseases, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China
- Bobo Wing-Yee Mok
- Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; State Key Laboratory for Emerging Infectious Diseases, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; Centre for Virology, Vaccinology and Therapeutics Limited, the University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
- Qiaoli Peng
- AIDS Institute, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; National Clinical Research Center for Infectious Diseases, The Third People's Hospital of Shenzhen and The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, People's Republic of China
- Na Liu
- AIDS Institute, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China
- Kin-Fai Woo
- AIDS Institute, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China
- Shaofeng Deng
- Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; State Key Laboratory for Emerging Infectious Diseases, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China
- Rachel Chun-Yee Tam
- Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; State Key Laboratory for Emerging Infectious Diseases, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China
- Haode Huang
- AIDS Institute, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China
- Anna Jinxia Zhang
- Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; State Key Laboratory for Emerging Infectious Diseases, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; Centre for Virology, Vaccinology and Therapeutics Limited, the University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
- Dongyan Zhou
- AIDS Institute, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; Centre for Virology, Vaccinology and Therapeutics Limited, the University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
- Biao Zhou
- AIDS Institute, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China
- Chun-Yin Chan
- AIDS Institute, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China
- Zhenglong Du
- AIDS Institute, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China
- Dawei Yang
- AIDS Institute, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China
- Ka-Kit Au
- AIDS Institute, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China
- Kwok-Yung Yuen
- Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; State Key Laboratory for Emerging Infectious Diseases, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; Centre for Virology, Vaccinology and Therapeutics Limited, the University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China; Department of Clinical Microbiology and Infection Control, the University of Hong Kong-Shenzhen Hospital; Shenzhen, Guangdong, People's Republic of China
- Honglin Chen
- Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; State Key Laboratory for Emerging Infectious Diseases, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; Centre for Virology, Vaccinology and Therapeutics Limited, the University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China; Department of Clinical Microbiology and Infection Control, the University of Hong Kong-Shenzhen Hospital; Shenzhen, Guangdong, People's Republic of China; Correspondence: Zhiwei Chen (Lead contact), and Honglin Chen, Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, L5-45, 21 Sassoon Road, Pokfulam, Hong Kong SAR, People's Republic of China, Phone: 852-3917-9831; Fax: 852-3917-7805.
- Zhiwei Chen
- AIDS Institute, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; State Key Laboratory for Emerging Infectious Diseases, the University of Hong Kong; Pokfulam, Hong Kong Special Administrative Region, People's Republic of China; Centre for Virology, Vaccinology and Therapeutics Limited, the University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China; Department of Clinical Microbiology and Infection Control, the University of Hong Kong-Shenzhen Hospital; Shenzhen, Guangdong, People's Republic of China; Correspondence: Zhiwei Chen (Lead contact), and Honglin Chen, Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, L5-45, 21 Sassoon Road, Pokfulam, Hong Kong SAR, People's Republic of China, Phone: 852-3917-9831; Fax: 852-3917-7805.
- Journal volume & issue
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Vol. 75
p. 103762
Abstract
Summary: Background: Vaccines in emergency use are efficacious against COVID-19, yet vaccine-induced prevention against nasal SARS-CoV-2 infection remains suboptimal. Methods: Since mucosal immunity is critical for nasal prevention, we investigated the efficacy of an intramuscular PD1-based receptor-binding domain (RBD) DNA vaccine (PD1-RBD-DNA) and intranasal live attenuated influenza-based vaccines (LAIV-CA4-RBD and LAIV-HK68-RBD) against SARS-CoV-2. Findings: Substantially higher systemic and mucosal immune responses, including bronchoalveolar lavage IgA/IgG and lung polyfunctional memory CD8 T cells, were induced by the heterologous PD1-RBD-DNA/LAIV-HK68-RBD as compared with other regimens. When vaccinated animals were challenged at the memory phase, prevention of robust SARS-CoV-2 infection in nasal turbinate was achieved primarily by the heterologous regimen besides consistent protection in lungs. The regimen-induced antibodies cross-neutralized variants of concerns. Furthermore, LAIV-CA4-RBD could boost the BioNTech vaccine for improved mucosal immunity. Interpretation: Our results demonstrated that intranasal influenza-based boost vaccination induces mucosal and systemic immunity for effective SARS-CoV-2 prevention in both upper and lower respiratory systems. Funding: This study was supported by the Research Grants Council Collaborative Research Fund, General Research Fund and Health and Medical Research Fund in Hong Kong; Outbreak Response to Novel Coronavirus (COVID-19) by the Coalition for Epidemic Preparedness Innovations; Shenzhen Science and Technology Program and matching fund from Shenzhen Immuno Cure BioTech Limited; the Health@InnoHK, Innovation and Technology Commission of Hong Kong; National Program on Key Research Project of China; donations from the Friends of Hope Education Fund; the Theme-Based Research Scheme.
