A Single-Dose Intranasal ChAd Vaccine Protects Upper and Lower Respiratory Tracts against SARS-CoV-2

Ahmed O. Hassan, Natasha M. Kafai, Igor P. Dmitriev, Julie M. Fox, Brittany K. Smith, Ian B. Harvey, Rita E. Chen, Emma S. Winkler, Alex W. Wessel, James Brett Case, Elena Kashentseva, Broc T. McCune, Adam L. Bailey, Haiyan Zhao, Laura A. VanBlargan, Ya Nan Dai, Meisheng Ma, Lucas J. Adams, Swathi Shrihari, Jonathan E. DanisLisa E. Gralinski, Yixuan J. Hou, Alexandra Schäfer, Arthur S. Kim, Shamus P. Keeler, Daniela Weiskopf, Ralph S. Baric, Michael J. Holtzman, Daved H. Fremont, David T. Curiel, Michael S. Diamond

Research output: Contribution to journalArticlepeer-review

380 Scopus citations


The coronavirus disease 2019 pandemic has made deployment of an effective vaccine a global health priority. We evaluated the protective activity of a chimpanzee adenovirus-vectored vaccine encoding a prefusion stabilized spike protein (ChAd-SARS-CoV-2-S) in challenge studies with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and mice expressing the human angiotensin-converting enzyme 2 receptor. Intramuscular dosing of ChAd-SARS-CoV-2-S induces robust systemic humoral and cell-mediated immune responses and protects against lung infection, inflammation, and pathology but does not confer sterilizing immunity, as evidenced by detection of viral RNA and induction of anti-nucleoprotein antibodies after SARS-CoV-2 challenge. In contrast, a single intranasal dose of ChAd-SARS-CoV-2-S induces high levels of neutralizing antibodies, promotes systemic and mucosal immunoglobulin A (IgA) and T cell responses, and almost entirely prevents SARS-CoV-2 infection in both the upper and lower respiratory tracts. Intranasal administration of ChAd-SARS-CoV-2-S is a candidate for preventing SARS-CoV-2 infection and transmission and curtailing pandemic spread.

Original languageEnglish
Pages (from-to)169-184.e13
Issue number1
StatePublished - Oct 1 2020


  • COVID-19
  • IgA
  • SARS-CoV-2
  • T cells
  • antibody
  • intranasal
  • mucosal immunity
  • pathogenesis
  • protection
  • vaccine


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