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A Single-Dose Intranasal ChAd Vaccine Protects Upper and Lower Respiratory Tracts against SARS-CoV-2.
Cell. 2020 10 01; 183(1):169-184.e13.Cell

Abstract

The coronavirus disease 2019 pandemic has made deployment of an effective vaccine a global health priority. We evaluated the protective activity of a chimpanzee adenovirus-vectored vaccine encoding a prefusion stabilized spike protein (ChAd-SARS-CoV-2-S) in challenge studies with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mice expressing the human angiotensin-converting enzyme 2 receptor. Intramuscular dosing of ChAd-SARS-CoV-2-S induces robust systemic humoral and cell-mediated immune responses and protects against lung infection, inflammation, and pathology but does not confer sterilizing immunity, as evidenced by detection of viral RNA and induction of anti-nucleoprotein antibodies after SARS-CoV-2 challenge. In contrast, a single intranasal dose of ChAd-SARS-CoV-2-S induces high levels of neutralizing antibodies, promotes systemic and mucosal immunoglobulin A (IgA) and T cell responses, and almost entirely prevents SARS-CoV-2 infection in both the upper and lower respiratory tracts. Intranasal administration of ChAd-SARS-CoV-2-S is a candidate for preventing SARS-CoV-2 infection and transmission and curtailing pandemic spread.

Authors+Show Affiliations

Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA.Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA.Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA.Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA.Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: dcuriel@wustl.edu.Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: diamond@wusm.wustl.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

32931734

Citation

Hassan, Ahmed O., et al. "A Single-Dose Intranasal ChAd Vaccine Protects Upper and Lower Respiratory Tracts Against SARS-CoV-2." Cell, vol. 183, no. 1, 2020, pp. 169-184.e13.
Hassan AO, Kafai NM, Dmitriev IP, et al. A Single-Dose Intranasal ChAd Vaccine Protects Upper and Lower Respiratory Tracts against SARS-CoV-2. Cell. 2020;183(1):169-184.e13.
Hassan, A. O., Kafai, N. M., Dmitriev, I. P., Fox, J. M., Smith, B. K., Harvey, I. B., Chen, R. E., Winkler, E. S., Wessel, A. W., Case, J. B., Kashentseva, E., McCune, B. T., Bailey, A. L., Zhao, H., VanBlargan, L. A., Dai, Y. N., Ma, M., Adams, L. J., Shrihari, S., ... Diamond, M. S. (2020). A Single-Dose Intranasal ChAd Vaccine Protects Upper and Lower Respiratory Tracts against SARS-CoV-2. Cell, 183(1), 169-e13. https://doi.org/10.1016/j.cell.2020.08.026
Hassan AO, et al. A Single-Dose Intranasal ChAd Vaccine Protects Upper and Lower Respiratory Tracts Against SARS-CoV-2. Cell. 2020 10 1;183(1):169-184.e13. PubMed PMID: 32931734.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Single-Dose Intranasal ChAd Vaccine Protects Upper and Lower Respiratory Tracts against SARS-CoV-2. AU - Hassan,Ahmed O, AU - Kafai,Natasha M, AU - Dmitriev,Igor P, AU - Fox,Julie M, AU - Smith,Brittany K, AU - Harvey,Ian B, AU - Chen,Rita E, AU - Winkler,Emma S, AU - Wessel,Alex W, AU - Case,James Brett, AU - Kashentseva,Elena, AU - McCune,Broc T, AU - Bailey,Adam L, AU - Zhao,Haiyan, AU - VanBlargan,Laura A, AU - Dai,Ya-Nan, AU - Ma,Meisheng, AU - Adams,Lucas J, AU - Shrihari,Swathi, AU - Danis,Jonathan E, AU - Gralinski,Lisa E, AU - Hou,Yixuan J, AU - Schäfer,Alexandra, AU - Kim,Arthur S, AU - Keeler,Shamus P, AU - Weiskopf,Daniela, AU - Baric,Ralph S, AU - Holtzman,Michael J, AU - Fremont,Daved H, AU - Curiel,David T, AU - Diamond,Michael S, Y1 - 2020/08/19/ PY - 2020/07/13/received PY - 2020/08/03/revised PY - 2020/08/14/accepted PY - 2020/9/16/pubmed PY - 2020/10/21/medline PY - 2020/9/15/entrez KW - COVID-19 KW - IgA KW - SARS-CoV-2 KW - T cells KW - antibody KW - intranasal KW - mucosal immunity KW - pathogenesis KW - protection KW - vaccine SP - 169 EP - 184.e13 JF - Cell JO - Cell VL - 183 IS - 1 N2 - The coronavirus disease 2019 pandemic has made deployment of an effective vaccine a global health priority. We evaluated the protective activity of a chimpanzee adenovirus-vectored vaccine encoding a prefusion stabilized spike protein (ChAd-SARS-CoV-2-S) in challenge studies with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mice expressing the human angiotensin-converting enzyme 2 receptor. Intramuscular dosing of ChAd-SARS-CoV-2-S induces robust systemic humoral and cell-mediated immune responses and protects against lung infection, inflammation, and pathology but does not confer sterilizing immunity, as evidenced by detection of viral RNA and induction of anti-nucleoprotein antibodies after SARS-CoV-2 challenge. In contrast, a single intranasal dose of ChAd-SARS-CoV-2-S induces high levels of neutralizing antibodies, promotes systemic and mucosal immunoglobulin A (IgA) and T cell responses, and almost entirely prevents SARS-CoV-2 infection in both the upper and lower respiratory tracts. Intranasal administration of ChAd-SARS-CoV-2-S is a candidate for preventing SARS-CoV-2 infection and transmission and curtailing pandemic spread. SN - 1097-4172 UR - https://www.unboundmedicine.com/medline/citation/32931734/A_Single_Dose_Intranasal_ChAd_Vaccine_Protects_Upper_and_Lower_Respiratory_Tracts_against_SARS_CoV_2_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0092-8674(20)31068-0 DB - PRIME DP - Unbound Medicine ER -