Abstract
In novel coronavirus infection (COVID-19), the outbreak of acute lung injury due to trans-airway infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the starting point of severe disease. The COVID-19 pandemic highlights the need for a vaccine that prevents not only the disease but also its infection. Currently, the SARS-CoV-2 vaccine is administered via intramuscular injection and is generally not immunogenic to the mucosa. As a result, current vaccinations fail to reduce viral shedding and transmission and ultimately do not prevent infection. We established a mouse vaccine model in which a single dose of S1 protein and aluminum oxide gel (alum) subcutaneous vaccine was followed by a booster dose of S1 protein and CpG oligodeoxynucleotide intranasal vaccine. The group that received two doses of the intranasal vaccine booster showed a significant increase in IgG and IgA antibody titers against S1 and RBD in serum and BAL, and a significant difference in neutralizing antibody titers, particularly in BAL. One intranasal vaccine booster did not induce sufficient immunity, and the vaccine strategy with two booster intranasal doses produced systemic neutralizing antibodies and mucus-neutralizing antibodies against SARS-CoV-2. It will be an important tool against the emergence of new viruses and the next pandemic.