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Induction of systemic, mucosal and cellular immunity against SARS-CoV-2 in mice intratracheally vaccinated with a viral S1 protein combined with a pulmonary surfactant-derived adjuvant SF-10
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  • Takashi Kimoto,
  • Satoko Sakai,
  • Keiko Kameda,
  • Ryoko Morita,
  • Etsuhisa Takahashi,
  • Yasuo Shinohara,
  • Hiroshi Kido
Takashi Kimoto
University of Tokushima

Corresponding Author:kimoto@tokushima-u.ac.jp

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Satoko Sakai
University of Tokushima
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Keiko Kameda
University of Tokushima
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Ryoko Morita
University of Tokushima
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Etsuhisa Takahashi
University of Tokushima
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Yasuo Shinohara
University of Tokushima
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Hiroshi Kido
University of Tokushima
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Abstract

Background There is a need for vaccines that can induce effective systemic, respiratory mucosal and cellular immunity to control the COVID-19 pandemic. We reported previously that a synthetic mucosal adjuvant SF-10 derived from human pulmonary surfactant works as an efficient antigen delivery vehicle to antigen presenting cells in the respiratory and gastrointestinal tracts and promotes induction of influenza virus antigen-specific serum IgG, mucosal IgA and cellular immunity. Methods The aim of the present study was to determine the effectiveness of a new administration method of intratracheal (IT) vaccine comprising recombinant SARS-CoV-2 spike protein 1 (S1) combined with SF-10 (S1-SF-10 vaccine) on systemic, local and cellular immunity in mice, compared with intramuscular injection (IM) of S1 with a potent adjuvant AS03 (S1-AS03 vaccine). Results S1-SF-10-IT vaccine induced S1-specific IgG and IgA in serum and lung mucosae. These IgG and IgA induced by S1-SF-10-IT showed significant protective immunity in a receptor binding inhibition test of S1 and angiotensin converting enzyme 2, a receptor of SARS-CoV-2, which were more potent and faster achievement than S1-AS03-IM. Enzyme-linked immunospot assay showed high numbers of S1-specific IgA and IgG secreting cells (ASCs) and S1-responsive IFN-γ, IL-4, IL-17A cytokine secreting cells (CSCs) in the spleen and lungs. S1-AS03-IM induced IgG ASCs and IL-4 CSCs in spleen higher than S1-SF10-IT, but the numbers of ASCs and CSCs in lungs were low and hardly detected. Conclusion Based on the need for effective systemic, respiratory and cellular immunity, the S1-SF-10-IT vaccine seems promising mucosal vaccine against respiratory infection of SARS-CoV-2.
08 Nov 2022Submitted to Influenza and other respiratory viruses
09 Nov 2022Submission Checks Completed
09 Nov 2022Assigned to Editor
02 Jan 2023Reviewer(s) Assigned
30 Jan 2023Review(s) Completed, Editorial Evaluation Pending
30 Jan 2023Editorial Decision: Revise Minor
14 Feb 20231st Revision Received
15 Feb 2023Submission Checks Completed
15 Feb 2023Assigned to Editor
16 Feb 2023Editorial Decision: Accept