Vaccines (Aug 2021)
Single-Dose Intranasal Administration of AdCOVID Elicits Systemic and Mucosal Immunity against SARS-CoV-2 and Fully Protects Mice from Lethal Challenge
- R. Glenn King,
- Aaron Silva-Sanchez,
- Jessica N. Peel,
- Davide Botta,
- Alexandria M. Dickson,
- Amelia K. Pinto,
- Selene Meza-Perez,
- S. Rameeza Allie,
- Michael D. Schultz,
- Mingyong Liu,
- John E. Bradley,
- Shihong Qiu,
- Guang Yang,
- Fen Zhou,
- Esther Zumaquero,
- Thomas S. Simpler,
- Betty Mousseau,
- John T. Killian,
- Brittany Dean,
- Qiao Shang,
- Jennifer L. Tipper,
- Christopher A. Risley,
- Kevin S. Harrod,
- Tsungwei Feng,
- Young Lee,
- Bethlehem Shiberu,
- Vyjayanthi Krishnan,
- Isabelle Peguillet,
- Jianfeng Zhang,
- Todd J. Green,
- Troy D. Randall,
- John J. Suschak,
- Bertrand Georges,
- James D. Brien,
- Frances E. Lund,
- M. Scot Roberts
Affiliations
- R. Glenn King
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Aaron Silva-Sanchez
- Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Jessica N. Peel
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Davide Botta
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Alexandria M. Dickson
- Department of Molecular Microbiology & Immunology, Saint Louis University, St. Louis, MO 63104, USA
- Amelia K. Pinto
- Department of Molecular Microbiology & Immunology, Saint Louis University, St. Louis, MO 63104, USA
- Selene Meza-Perez
- Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- S. Rameeza Allie
- Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Michael D. Schultz
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Mingyong Liu
- Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- John E. Bradley
- Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Shihong Qiu
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Guang Yang
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Fen Zhou
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Esther Zumaquero
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Thomas S. Simpler
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Betty Mousseau
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- John T. Killian
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Brittany Dean
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Qiao Shang
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Jennifer L. Tipper
- Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Christopher A. Risley
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Kevin S. Harrod
- Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Tsungwei Feng
- Altimmune Inc., Gaithersburg, MD 20878, USA
- Young Lee
- Altimmune Inc., Gaithersburg, MD 20878, USA
- Bethlehem Shiberu
- Altimmune Inc., Gaithersburg, MD 20878, USA
- Vyjayanthi Krishnan
- Altimmune Inc., Gaithersburg, MD 20878, USA
- Isabelle Peguillet
- Altimmune Inc., Gaithersburg, MD 20878, USA
- Jianfeng Zhang
- Altimmune Inc., Gaithersburg, MD 20878, USA
- Todd J. Green
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Troy D. Randall
- Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- John J. Suschak
- Altimmune Inc., Gaithersburg, MD 20878, USA
- Bertrand Georges
- Altimmune Inc., Gaithersburg, MD 20878, USA
- James D. Brien
- Department of Molecular Microbiology & Immunology, Saint Louis University, St. Louis, MO 63104, USA
- Frances E. Lund
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- M. Scot Roberts
- Altimmune Inc., Gaithersburg, MD 20878, USA
- DOI
- https://doi.org/10.3390/vaccines9080881
- Journal volume & issue
-
Vol. 9,
no. 8
p. 881
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.
Keywords
