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
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.
