The coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need for effective prophylactic vaccination to prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Intranasal vaccination is an attractive strategy to prevent COVID-19 as the nasal mucosa represents the first-line barrier to SARS-CoV-2 entry. The current intramuscular vaccines elicit systemic immunity but not necessarily high-level mucosal immunity. Here, we tested a single intranasal dose of our candidate adenovirus type 5-vectored vaccine encoding the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein (AdCOVID) in inbred, outbred, and transgenic mice. A single intranasal vaccination with AdCOVID elicited a strong and focused immune response against RBD through the induction of mucosal IgA in the respiratory tract, serum neutralizing antibodies, and CD4 + and CD8 + T cells with a T h 1-like cytokine expression profile. A single AdCOVID dose resulted in immunity that was sustained for over six months. Moreover, a single intranasal dose completely protected K18-hACE2 mice from lethal SARS-CoV-2 challenge, preventing weight loss and mortality. These data show that AdCOVID promotes concomitant systemic and mucosal immunity and represents a promising vaccine candidate.
【저자키워드】 COVID-19, Viral vector, SARS-CoV-2, Vaccine, Receptor binding domain, IgA, mucosal immunity, intranasal, Adenovirus Vector, 【초록키워드】 coronavirus disease, coronavirus, immune response, vaccination, pandemic, Mortality, Immunity, Neutralizing antibodies, Prophylactic, CD4, CD8, Spike protein, Adenovirus, Spread, serum, T cell, RBD, vaccine candidate, K18-hACE2 mice, respiratory tract, nasal mucosa, intramuscular, mucosal, dose, weight loss, acute respiratory syndrome, SARS-CoV-2 entry, transgenic mice, Prevent, effective, tested, elicit, promote, the receptor-binding domain, elicited, sustained, cytokine expression profile, the SARS-CoV-2, 【제목키워드】 challenge, systemic, lethal,