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

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish
Article number109452
JournalCell Reports
Volume36
Issue number4
DOIs
StatePublished - Jul 27 2021

Keywords

  • COVID-19
  • SARS-CoV-2
  • antibody
  • durability
  • mice
  • mucosal immunity
  • pathogenesis
  • vaccine
  • variants of concern

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