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

Year: 2021
Type: article
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.
Source: Cell Reports
DOI: 10.1016/j.celrep.2021.109452
Authors: 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
Institutions: Washington University in St. Louis, Harvard University, Ragon Institute of MGH, MIT and Harvard, Massachusetts Institute of Technology, La Jolla Institute for Immunology, Emory University, Children's Healthcare of Atlanta, The University of Texas Medical Branch at Galveston
Language: English
Field: Medicine
Open Access status: gold
Estimated APC paid: $8,994
Funders: Bill and Melinda Gates Foundation, Moderna, Institut National de la Santé et de la Recherche Médicale, National Institutes of Health, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Biomedical Imaging and Bioengineering
Awards: Human antibody-based countermeasures against the Wuhan Coronavirus SARS-CoV-2, G1434356123, G3041239396, G4587763221, Novel Vector Platform for Gene Therapy, G530559849, G5514976981, G5571277077, G5990125371, National Research Service Award-Medical Scientist, G7941798282
OpenAlex ID: W3179359240
FWCI: 8.307
Cites: 74
Cited by: 125
Related to: 10