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

Peter Zhou; Jacqueline Watt; Juntao Mai; Huibi Cao; Zhijie Li; Ziyan Chen; Rongqi Duan; Ying Quan; Anne-Claude Gingras; James M Rini; Jim Hu; Jun Liu

doi:10.3389/fimmu.2024.1430928

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

Front Immunol. 2024 Aug 30:15:1430928. doi: 10.3389/fimmu.2024.1430928. eCollection 2024.

Authors

Peter Zhou^#¹, Jacqueline Watt^#¹, Juntao Mai¹, Huibi Cao², Zhijie Li¹, Ziyan Chen^{2

3}, Rongqi Duan², Ying Quan¹, Anne-Claude Gingras^{1

4}, James M Rini^{1

5}, Jim Hu^{2

3}, Jun Liu¹

Affiliations

¹ Department of Molecular Genetics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
² Translational Medicine Program, Hospital for Sick Children Research Institute, Toronto, ON, Canada.
³ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
⁴ Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
⁵ Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.

^# Contributed equally.

Abstract

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; SARS-CoV-2; adenoviral vector; intranasal delivery; vaccine.

MeSH terms

Adenoviridae / genetics
Adenoviridae / immunology
Administration, Intranasal*
Angiotensin-Converting Enzyme 2 / genetics
Angiotensin-Converting Enzyme 2 / immunology
Angiotensin-Converting Enzyme 2 / metabolism
Animals
Antibodies, Neutralizing* / blood
Antibodies, Neutralizing* / immunology
Antibodies, Viral* / blood
Antibodies, Viral* / immunology
COVID-19 Vaccines* / administration & dosage
COVID-19 Vaccines* / immunology
COVID-19* / immunology
COVID-19* / prevention & control
Cricetinae
Female
Humans
Immunity, Mucosal*
Mesocricetus
Mice
Mice, Inbred BALB C*
Mice, Transgenic
SARS-CoV-2* / immunology
Spike Glycoprotein, Coronavirus* / genetics
Spike Glycoprotein, Coronavirus* / immunology

Substances

COVID-19 Vaccines
Spike Glycoprotein, Coronavirus
Antibodies, Viral
Antibodies, Neutralizing
spike protein, SARS-CoV-2
Angiotensin-Converting Enzyme 2

Supplementary concepts

SARS-CoV-2 variants

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by Canadian Institutes of Health Research (CIHR) grants, VR1-172771, VS-1-175531, GA-2-177717, and Covid-19 Immunity Task Force (CITF).