Abstract
The new coronavirus infection causes severe respiratory failure following respiratory tract infection with severe acute respiratory syndrome-related coronavirus (SARS-CoV-2). All currently approved vaccines are administered intramuscularly; however, intranasal administration enhances mucosal immunity, facilitating the production of a less invasive vaccine with fewer adverse events. Herein, a recombinant vaccine combining the SARS-CoV-2 spike protein receptor-binding domain (RBD), or S1 protein, with CpG-deoxyoligonucleotide (ODN) or aluminum hydroxide (alum) adjuvants was administered intranasally or subcutaneously to mice. Serum-specific IgG titers, IgA titers in the alveolar lavage fluid, and neutralizing antibody titers were analyzed. The nasal administration of RBD protein did not increase serum IgG or IgA titers in the alveolar lavage fluid. However, a significant increase in serum IgG was observed in the intranasal group administered with S1 protein with CpG-ODN and the subcutaneous group administered with S1 protein with alum. The IgA and IgG levels increased significantly in the alveolar lavage fluid only after the intranasal administration of the S1 protein with CpG-ODN. The neutralizing antibody titers in serum and bronchoalveolar lavage were significantly higher in the intranasal S1-CpG group than in every other group. Hence, the nasal administration of the S1 protein vaccine with CpG adjuvant might represent an effective vaccine candidate.