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Nasal prevention of SARS-CoV-2 infection by intranasal influenza-based boost vaccination in mouse models.
EBioMedicine. 2022 Jan; 75:103762.E

Abstract

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.

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Authors+Show Affiliations

Zhou R
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.
Wang P
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.
Wong YC
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.
Xu H
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.
Lau SY
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.
Liu L
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.
Mok BW
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.
Peng Q
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.
Liu N
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.
Woo KF
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.
Deng S
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.
Tam RC
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.
Huang H
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.
Zhang AJ
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.
Zhou D
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.
Zhou B
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.
Chan CY
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.
Du Z
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.
Yang D
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.
Au KK
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.
Yuen KY
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.
Chen H
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. Electronic address: hlchen@hku.hk.
Chen Z
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. Electronic address: zchenai@hku.hk.

MeSH

Administration, IntranasalAnimalsCOVID-19COVID-19 VaccinesChlorocebus aethiopsDisease Models, AnimalDogsFemaleHEK293 CellsHumansImmunity, MucosalImmunization, SecondaryInfluenza VaccinesMadin Darby Canine Kidney CellsMaleMiceMice, Inbred BALB CMice, TransgenicSARS-CoV-2Vaccines, AttenuatedVaccines, DNAVero Cells

Pub Type(s)

Journal Article

Language

eng

PubMed ID

34942445

Citation

Zhou, Runhong, et al. "Nasal Prevention of SARS-CoV-2 Infection By Intranasal Influenza-based Boost Vaccination in Mouse Models." EBioMedicine, vol. 75, 2022, p. 103762.
Zhou R, Wang P, Wong YC, et al. Nasal prevention of SARS-CoV-2 infection by intranasal influenza-based boost vaccination in mouse models. EBioMedicine. 2022;75:103762.
Zhou, R., Wang, P., Wong, Y. C., Xu, H., Lau, S. Y., Liu, L., Mok, B. W., Peng, Q., Liu, N., Woo, K. F., Deng, S., Tam, R. C., Huang, H., Zhang, A. J., Zhou, D., Zhou, B., Chan, C. Y., Du, Z., Yang, D., ... Chen, Z. (2022). Nasal prevention of SARS-CoV-2 infection by intranasal influenza-based boost vaccination in mouse models. EBioMedicine, 75, 103762. https://doi.org/10.1016/j.ebiom.2021.103762
Zhou R, et al. Nasal Prevention of SARS-CoV-2 Infection By Intranasal Influenza-based Boost Vaccination in Mouse Models. EBioMedicine. 2022;75:103762. PubMed PMID: 34942445.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nasal prevention of SARS-CoV-2 infection by intranasal influenza-based boost vaccination in mouse models. AU - Zhou,Runhong, AU - Wang,Pui, AU - Wong,Yik-Chun, AU - Xu,Haoran, AU - Lau,Siu-Ying, AU - Liu,Li, AU - Mok,Bobo Wing-Yee, AU - Peng,Qiaoli, AU - Liu,Na, AU - Woo,Kin-Fai, AU - Deng,Shaofeng, AU - Tam,Rachel Chun-Yee, AU - Huang,Haode, AU - Zhang,Anna Jinxia, AU - Zhou,Dongyan, AU - Zhou,Biao, AU - Chan,Chun-Yin, AU - Du,Zhenglong, AU - Yang,Dawei, AU - Au,Ka-Kit, AU - Yuen,Kwok-Yung, AU - Chen,Honglin, AU - Chen,Zhiwei, Y1 - 2021/12/21/ PY - 2021/07/29/received PY - 2021/11/11/revised PY - 2021/12/02/accepted PY - 2021/12/24/pubmed PY - 2022/2/2/medline PY - 2021/12/23/entrez KW - Live-attenuated influenza-based vaccine KW - Mucosal immunity KW - Nasal prevention KW - PD1-based DNA vaccine KW - Receptor binding domain KW - SARS-CoV-2 SP - 103762 EP - 103762 JF - EBioMedicine JO - EBioMedicine VL - 75 N2 - 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. SN - 2352-3964 UR - https://www.unboundmedicine.com/medline/citation/34942445/Nasal_prevention_of_SARS_CoV_2_infection_by_intranasal_influenza_based_boost_vaccination_in_mouse_models_ DB - PRIME DP - Unbound Medicine ER -