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

Ahmed O Hassan; Swathi Shrihari; Matthew J Gorman; Baoling Ying; Dansu Yuan; 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

doi:10.1016/j.celrep.2021.109452

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

Cell Rep. 2021 Jul 27;36(4):109452. doi: 10.1016/j.celrep.2021.109452. Epub 2021 Jul 10.

Authors

Ahmed O Hassan¹, Swathi Shrihari¹, Matthew J Gorman², Baoling Ying¹, Dansu Yuan², Saravanan Raju³, Rita E Chen³, Igor P Dmitriev⁴, Elena Kashentseva⁴, Lucas J Adams⁵, Colin Mann⁶, Meredith E Davis-Gardner⁷, Mehul S Suthar⁷, Pei-Yong Shi⁸, Erica Ollmann Saphire⁶, Daved H Fremont⁹, David T Curiel⁴, Galit Alter², Michael S Diamond¹⁰

Affiliations

¹ Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
² Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology, and Harvard University, Cambridge, MA, USA.
³ 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.
⁴ Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA.
⁵ Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
⁶ La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
⁷ 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.
⁸ 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.
⁹ 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.
¹⁰ 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. Electronic address: [email protected].

Abstract

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.

Keywords: COVID-19; SARS-CoV-2; antibody; durability; mice; mucosal immunity; pathogenesis; vaccine; variants of concern.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Administration, Intranasal / methods
Animals
Antibodies, Neutralizing / immunology
Antibodies, Neutralizing / pharmacology*
Antibodies, Viral / immunology
Antibodies, Viral / pharmacology
Mice
SARS-CoV-2 / pathogenicity*
Spike Glycoprotein, Coronavirus / immunology*
Vaccination / methods
Viral Vaccines / immunology
Viral Vaccines / pharmacology*

Substances

Antibodies, Neutralizing
Antibodies, Viral
Spike Glycoprotein, Coronavirus
Viral Vaccines

Abstract

Publication types

MeSH terms

Substances

Grants and funding