An intranasal vaccine durably protects against SARS-CoV-2 variants in mice

Ahmed O. Hassan; Swathi Shrihari; Matthew J. Gorman; Baoling Ying; Dansu Yaun; Saravanan Raju; Rita E. Chen; Igor P. Dmitriev; Elena Kashentseva; Lucas J. Adams; Colin Mann; Meredith E. Davis-Gardner; Mehul S. Suthar; Pei-Yong Shi; Erica Ollmann Saphire; Daved H. Fremont; David T. Curiel; Galit Alter; Michael S. Diamond

Cell Reports (Jul 2021)

An intranasal vaccine durably protects against SARS-CoV-2 variants in mice

Ahmed O. Hassan,
Swathi Shrihari,
Matthew J. Gorman,
Baoling Ying,
Dansu Yaun,
Saravanan Raju,
Rita E. Chen,
Igor P. Dmitriev,
Elena Kashentseva,
Lucas J. Adams,
Colin Mann,
Meredith E. Davis-Gardner,
Mehul S. Suthar,
Pei-Yong Shi,
Erica Ollmann Saphire,
Daved H. Fremont,
David T. Curiel,
Galit Alter,
Michael S. Diamond

Affiliations

Ahmed O. Hassan: Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Swathi Shrihari: Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Matthew J. Gorman: Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology, and Harvard University, Cambridge, MA, USA
Baoling Ying: Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Dansu Yaun: Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology, and Harvard University, Cambridge, MA, USA
Saravanan Raju: 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
Rita E. Chen: 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
Igor P. Dmitriev: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA
Elena Kashentseva: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA
Lucas J. Adams: Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
Colin Mann: La Jolla Institute for Immunology, La Jolla, CA 92037, USA
Meredith E. Davis-Gardner: Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Department of Pediatrics, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA
Mehul S. Suthar: Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Department of Pediatrics, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA
Pei-Yong Shi: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Departments of Microbiology and Immunology, University of Texas Medical Branch, Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA
Erica Ollmann Saphire: La Jolla Institute for Immunology, La Jolla, CA 92037, USA
Daved H. Fremont: Department of Pathology & Immunology, 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 Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA
David T. Curiel: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA
Galit Alter: Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology, and Harvard University, Cambridge, MA, USA
Michael S. Diamond: 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 and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA; Corresponding author

Journal volume & issue: Vol. 36, no. 4
p. 109452

Abstract

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Summary: SARS-CoV-2 variants that attenuate antibody neutralization could jeopardize vaccine efficacy. We recently reported the protective activity of an intranasally administered spike protein-based chimpanzee adenovirus-vectored vaccine (ChAd-SARS-CoV-2-S) in animals, which has advanced to human trials. Here, we assessed its durability, dose response, and cross-protective activity in mice. A single intranasal dose of ChAd-SARS-CoV-2-S induced durably high neutralizing and Fc effector antibody responses in serum and S-specific IgG and IgA secreting long-lived plasma cells in the bone marrow. Protection against a historical SARS-CoV-2 strain was observed across a 100-fold vaccine dose range and over a 200-day period. At 6 weeks or 9 months after vaccination, serum antibodies neutralized SARS-CoV-2 strains with B.1.351, B.1.1.28, and B.1.617.1 spike proteins and conferred almost complete protection in the upper and lower respiratory tracts after challenge with variant viruses. Thus, in mice, intranasal immunization with ChAd-SARS-CoV-2-S provides durable protection against historical and emerging SARS-CoV-2 strains.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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