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

tetano

Editor, Senior Moderator
Cell


. 2020 Aug 19;S0092-8674(20)31068-0.
doi: 10.1016/j.cell.2020.08.026. Online ahead of print.
A Single-Dose Intranasal ChAd Vaccine Protects Upper and Lower Respiratory Tracts against SARS-CoV-2


Ahmed O Hassan[SUP] 1 [/SUP], Natasha M Kafai[SUP] 2 [/SUP], Igor P Dmitriev[SUP] 3 [/SUP], Julie M Fox[SUP] 1 [/SUP], Brittany K Smith[SUP] 4 [/SUP], Ian B Harvey[SUP] 5 [/SUP], Rita E Chen[SUP] 2 [/SUP], Emma S Winkler[SUP] 2 [/SUP], Alex W Wessel[SUP] 2 [/SUP], James Brett Case[SUP] 1 [/SUP], Elena Kashentseva[SUP] 3 [/SUP], Broc T McCune[SUP] 1 [/SUP], Adam L Bailey[SUP] 5 [/SUP], Haiyan Zhao[SUP] 5 [/SUP], Laura A VanBlargan[SUP] 1 [/SUP], Ya-Nan Dai[SUP] 5 [/SUP], Meisheng Ma[SUP] 5 [/SUP], Lucas J Adams[SUP] 5 [/SUP], Swathi Shrihari[SUP] 1 [/SUP], Jonathan E Danis[SUP] 5 [/SUP], Lisa E Gralinski[SUP] 6 [/SUP], Yixuan J Hou[SUP] 6 [/SUP], Alexandra Sch?fer[SUP] 6 [/SUP], Arthur S Kim[SUP] 2 [/SUP], Shamus P Keeler[SUP] 7 [/SUP], Daniela Weiskopf[SUP] 8 [/SUP], Ralph S Baric[SUP] 9 [/SUP], Michael J Holtzman[SUP] 10 [/SUP], Daved H Fremont[SUP] 11 [/SUP], David T Curiel[SUP] 12 [/SUP], Michael S Diamond[SUP] 13 [/SUP]



Affiliations

Abstract

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.

Keywords: COVID-19; IgA; SARS-CoV-2; T cells; antibody; intranasal; mucosal immunity; pathogenesis; protection; vaccine.
 
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