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Single-Dose Intranasal Administration of AdCOVID Elicits Systemic and Mucosal Immunity against SARS-CoV-2 and Fully Protects Mice from Lethal Challenge

1
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
2
Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
3
Department of Molecular Microbiology & Immunology, Saint Louis University, St. Louis, MO 63104, USA
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Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
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Altimmune Inc., Gaithersburg, MD 20878, USA
*
Authors to whom correspondence should be addressed.
These authors contributed equally.
Academic Editor: Ger Rijkers
Vaccines 2021, 9(8), 881; https://doi.org/10.3390/vaccines9080881
Received: 23 June 2021 / Revised: 29 July 2021 / Accepted: 3 August 2021 / Published: 9 August 2021
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. View Full-Text
Keywords: COVID-19; SARS-CoV-2; receptor binding domain; vaccine; adenovirus vector; viral vector; intranasal; mucosal immunity; IgA COVID-19; SARS-CoV-2; receptor binding domain; vaccine; adenovirus vector; viral vector; intranasal; mucosal immunity; IgA
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MDPI and ACS Style

King, R.G.; Silva-Sanchez, A.; Peel, J.N.; Botta, D.; Dickson, A.M.; Pinto, A.K.; Meza-Perez, S.; Allie, S.R.; Schultz, M.D.; Liu, M.; Bradley, J.E.; Qiu, S.; Yang, G.; Zhou, F.; Zumaquero, E.; Simpler, T.S.; Mousseau, B.; Killian, J.T., Jr.; Dean, B.; Shang, Q.; Tipper, J.L.; Risley, C.A.; Harrod, K.S.; Feng, T.; Lee, Y.; Shiberu, B.; Krishnan, V.; Peguillet, I.; Zhang, J.; Green, T.J.; Randall, T.D.; Suschak, J.J.; Georges, B.; Brien, J.D.; Lund, F.E.; Roberts, M.S. Single-Dose Intranasal Administration of AdCOVID Elicits Systemic and Mucosal Immunity against SARS-CoV-2 and Fully Protects Mice from Lethal Challenge. Vaccines 2021, 9, 881. https://doi.org/10.3390/vaccines9080881

AMA Style

King RG, Silva-Sanchez A, Peel JN, Botta D, Dickson AM, Pinto AK, Meza-Perez S, Allie SR, Schultz MD, Liu M, Bradley JE, Qiu S, Yang G, Zhou F, Zumaquero E, Simpler TS, Mousseau B, Killian JT Jr., Dean B, Shang Q, Tipper JL, Risley CA, Harrod KS, Feng T, Lee Y, Shiberu B, Krishnan V, Peguillet I, Zhang J, Green TJ, Randall TD, Suschak JJ, Georges B, Brien JD, Lund FE, Roberts MS. Single-Dose Intranasal Administration of AdCOVID Elicits Systemic and Mucosal Immunity against SARS-CoV-2 and Fully Protects Mice from Lethal Challenge. Vaccines. 2021; 9(8):881. https://doi.org/10.3390/vaccines9080881

Chicago/Turabian Style

King, R. G., Aaron Silva-Sanchez, Jessica N. Peel, Davide Botta, Alexandria M. Dickson, Amelia K. Pinto, Selene Meza-Perez, S. R. 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 Jr., 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, and M. S. Roberts. 2021. "Single-Dose Intranasal Administration of AdCOVID Elicits Systemic and Mucosal Immunity against SARS-CoV-2 and Fully Protects Mice from Lethal Challenge" Vaccines 9, no. 8: 881. https://doi.org/10.3390/vaccines9080881

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