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 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.
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 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.
Subject(s)
COVID-19 , Pulmonary Surfactants , Humans , Animals , Mice , Pulmonary Surfactants/pharmacology , SARS-CoV-2 , Interleukin-4/pharmacology , Pandemics , Immunity, Mucosal , Antibodies, Viral , Adjuvants, Immunologic , Immunity, Cellular , Immunoglobulin A/pharmacology , Immunoglobulin GABSTRACT
Human influenza virus infections occur annually worldwide and are associated with high morbidity and mortality. Hence, development of novel anti-influenza drugs is urgently required. Rice Power® extract developed by the Yushin Brewer Co. Ltd. is a novel aqueous extract of rice obtained via saccharization and fermentation with various microorganisms, such as Aspergillus oryzae, yeast [such as Saccharomyces cerevisiae], and lactic acid bacteria, possessing various biological and pharmacological properties. In our previous experimental screening with thirty types of Rice Power® extracts, we observed that the 30th Rice Power® (Y30) extract promoted the survival of influenza A virus-infected Madin-Darby canine kidney (MDCK) cells. Therefore, to identify compounds for the development of novel anti-influenza drugs, we aimed to investigate whether the Y30 extract exhibits anti-influenza A virus activity. In the present study, we demonstrated that the Y30 extract strongly promoted the survival of influenza A H1N1 Puerto Rico 8/34 (A/PR/8/34), California 7/09, or H3N2 Aichi 2/68 (A/Aichi/2/68) viruses-infected MDCK cells and inhibited A/PR/8/34 or A/Aichi/2/68 viruses infection and growth in the co-treatment and pre-infection experiments. The pre-treatment of Y30 extract on MDCK cells did not induce anti-influenza activity in the cell. The Y30 extract did not significantly affect influenza A virus hemagglutination, and neuraminidase and RNA-dependent RNA polymerase activities. Interestingly, the electron microscopy experiment revealed that the Y30 extract disrupts the integrity of influenza A virus particles by permeabilizing the viral membrane envelope, suggesting that Y30 extract has a direct virucidal effect against influenza A virus. Furthermore, we observed that compared to the ethyl acetate (EtOAc) extract, the water extract of Y30 extract considerably promoted the survival of cells infected with A/PR/8/34 virus. These results indicated that more anti-influenza components were present in the water extract of Y30 extract than in the EtOAc extract. Our results highlight the potential of a rice extract fermented with A. oryzae and S. cerevisiae as an anti-influenza medicine and a drug source for the development of anti-influenza compounds.