Abstract
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 Th1-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.
Highlights
First reported in late 2019 in China, severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) evolved into a global pandemic within a few months [1]
The intranasal COVID-19 vaccine candidate is based on a replication-deficient E1and E3-deleted Ad5 vector platform [32]
Given the potent neutralizing antibody titers measured in AdCOVID vaccinated mice, we evaluated the ability of AdCOVID to elicit cellular immunity
Summary
First reported in late 2019 in China, severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) evolved into a global pandemic within a few months [1]. First reported in late 2019 in China, severe acute respiratory syndrome coronavirus 2. The World Health Organization estimates over 178 million cases of coronavirus disease. The global impact on human health and well-being underscores the immediate need for safe and effective vaccines against SARS-CoV-2 to end this pandemic and prevent its return. Despite the well-recognized role of mucosal immunity in prevention of disease [10,11], all of the COVID-19 vaccines granted emergency use authorization or have been advanced to Phase 3 clinical trials are administered via intramuscular injection [12,13,14,15]. Intramuscular injection elicits systemic immunity but does not result in potent mucosal immune responses
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