Journal
VACCINES
Volume 9, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/vaccines9080881
Keywords
COVID-19; SARS-CoV-2; receptor binding domain; vaccine; adenovirus vector; viral vector; intranasal; mucosal immunity; IgA
Categories
Funding
- Altimmune Inc.
- Barbara Ingalls Shook Foundation
- NIH/NCI [1U01CA260541-01]
- [U19 3U19AI142737]
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The study found that a single intranasal dose of AdCOVID vaccine can generate a strong and focused immune response against RBD, including mucosal IgA in the respiratory tract, serum neutralizing antibodies, and CD4(+) and CD8(+) T cells with a T(h)1-like cytokine expression profile. Additionally, a single AdCOVID dose can result in immunity sustained for over six months and completely protect K18-hACE2 mice from lethal SARS-CoV-2 challenge, preventing weight loss and mortality, indicating that AdCOVID promotes concomitant systemic and mucosal immunity and serves as a promising vaccine candidate.
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.
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