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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1430928
This article is part of the Research Topic Immune studies of SARS-CoV2 and vaccines using preclinical modeling View all 8 articles
Intranasal HD-Ad-FS Vaccine Induces Systemic and Airway Mucosal Immunities Against SARS-CoV-2 and Systemic Immunity against SARS-CoV-2 Variants in Mice and Hamsters
Provisionally accepted
Zhichang P. Zhou
1
Jacqueline Watt
1
Juntao Mai
1
Huibi Cao
2*
Zhijie Li
1
Ziyan Chen
1,2
Rongqi Duan
2*
Ying Quan
1*
Anne-Claude Gingras
1,3
James M. Rini
1*
Jim Hu
1,2*
Jun Liu
1*- 1 University of Toronto, Toronto, Canada
- 2 Sick Kids Research Institute, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
- 3 Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
The outbreak of coronavirus disease 19 (COVID-19) has highlighted the demand for vaccines that are safe and effective in inducing systemic and airway mucosal immunity against the aerosol transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, we developed a novel helper-dependent adenoviral vector-based COVID-19 mucosal vaccine encoding a full-length SARS-CoV-2 spike protein (HD-Ad-FS). Through intranasal immunization (single-dose and prime-boost regimens), we demonstrated that the HD-Ad-FS was immunogenic and elicited potent systemic and airway mucosal protection in BALB/c mice, transgenic ACE2 (hACE2) mice, and hamsters. We detected high titers of neutralizing antibodies (NAbs) in sera and bronchoalveolar lavages (BALs) in the vaccinated animals. High levels of spike-specific secretory IgA (sIgA) and IgG were induced in the airway of the vaccinated animals. The single-dose HD-Ad-FS elicited a strong immune response and protected animals from SARS-CoV-2 infection. In addition, the prime-boost vaccination induced cross-reactive serum NAbs against variants of concern (VOCs; Beta, Delta, and Omicron). After challenge, VOC infectious viral particles were at undetectable or minimal levels in the lower airway. Our findings highlight the potential of airway delivery of HD-Ad-FS as a safe and effective vaccine platform for generating mucosal protection against SARS-CoV-2 and its VOCs.
Keywords: COVID-19, HD-Ad, Adenoviral vector, Intranasal delivery, SARS-CoV-2, Vaccine
Received: 10 May 2024; Accepted: 08 Aug 2024.
Copyright: © 2024 Zhou, Watt, Mai, Cao, Li, Chen, Duan, Quan, Gingras, Rini, Hu and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Huibi Cao, Sick Kids Research Institute, Hospital for Sick Children, University of Toronto, Toronto, M5G 1X8, Ontario, Canada
Rongqi Duan, Sick Kids Research Institute, Hospital for Sick Children, University of Toronto, Toronto, M5G 1X8, Ontario, Canada
Ying Quan, University of Toronto, Toronto, Canada
James M. Rini, University of Toronto, Toronto, Canada
Jim Hu, University of Toronto, Toronto, Canada
Jun Liu, University of Toronto, Toronto, Canada
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.