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.
| Original language | English |
|---|---|
| Article number | 881 |
| Journal | Vaccines |
| Volume | 9 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 2021 |
Bibliographical note
Publisher Copyright:© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Funding
Conflicts of Interest: Investigators at The University of Alabama at Birmingham (UAB: F.E.L. as project lead) and St. Louis University (SLU: J.D.B. as project lead) were funded by a sponsored research agreement from Altimmune to perform these studies. F.E.L., R.G.K. and T.D.R. serve as paid consultants for Altimmune. B.G., S.R., J.J.S., T.F., Y.L., B.S., V.K., I.P. and J.Z. are employees of Altimmune Inc. and may have received stock options and compensation as part of their employment. All other authors declare no potential conflicts of interest. Funding: Altimmune Inc. and the Barbara Ingalls Shook Foundation (to FEL) provided funding for the work reported in this article. Support for the development and validation of SARS-CoV-2 spike cytometric bead arrays was provided by U19 3U19AI142737 (to F.E.L., R.G.K., T.J.G., T.D.R.). Support for the development of the SARS-CoV-2 challenge model and FRNT was provided by NIH/NCI 1U01CA260541-01 (to J.D.B). Altimmune Inc. and the Barbara Ingalls Shook Foundation (to FEL) provided funding for the work reported in this article. Support for the development and validation of SARS-CoV-2 spike cytometric bead arrays was provided by U19 3U19AI142737 (to F.E.L., R.G.K., T.J.G., T.D.R.). Support for the development of the SARS-CoV-2 challenge model and FRNT was provided by NIH/NCI 1U01CA260541-01 (to J.D.B).
| Funders | Funder number |
|---|---|
| Altimmune Inc | |
| Barbara Ingalls Shook Foundation | U19 3U19AI142737 |
| National Institutes of Health (NIH) | |
| National Childhood Cancer Registry – National Cancer Institute | 1U01CA260541-01 |
| National Childhood Cancer Registry – National Cancer Institute | |
| Division of Bone and Mineral Diseases, John T. Milliken Department of Medicine, Washington University in St. Louis | |
| Sveriges Lantbruksuniversitet |
Keywords
- Adenovirus vector
- COVID-19
- IgA
- Intranasal
- Mucosal immunity
- Receptor binding domain
- SARS-CoV-2
- Vaccine
- Viral vector
ASJC Scopus subject areas
- Immunology
- Pharmacology
- Drug Discovery
- Infectious Diseases
- Pharmacology (medical)
