Induction of systemic, mucosal, and cellular immunity against SARS‐CoV‐2 in mice vaccinated by trans‐airway with a S1 protein combined with a pulmonary surfactant‐derived adjuvant SF‐10

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 route of trans‐airway (TA) 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 AddaS03™ (S1‐AddaS03™ vaccine). RESULTS: S1‐SF‐10‐TA vaccine induced S1‐specific IgG and IgA in serum and lung mucosae. These IgG and IgA induced by S1‐SF‐10‐TA 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‐AddaS03™‐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‐AddaS03™‐IM induced IgG ASCs and IL‐4 CSCs in spleen higher than S1‐SF‐10‐TA, but the numbers of ASCs and CSCs in lungs were low and hardly detected. CONCLUSIONS: Based on the need for effective systemic, respiratory, and cellular immunity, the S1‐SF‐10‐TA vaccine seems promising mucosal vaccine against respiratory infection of SARS‐CoV‐2.