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

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 respir...

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Published in:Cell Vol. 183; no. 1; p. 169
Main Authors: Hassan, Ahmed O, Kafai, Natasha M, Dmitriev, Igor P, Fox, Julie M, Smith, Brittany K, Harvey, Ian B, Chen, Rita E, Winkler, Emma S, Wessel, Alex W, Case, James Brett, Kashentseva, Elena, McCune, Broc T, Bailey, Adam L, Zhao, Haiyan, VanBlargan, Laura A, Dai, Ya-Nan, Ma, Meisheng, Adams, Lucas J, Shrihari, Swathi, Danis, Jonathan E, Gralinski, Lisa E, Hou, Yixuan J, Schäfer, Alexandra, Kim, Arthur S, Keeler, Shamus P, Weiskopf, Daniela, Baric, Ralph S, Holtzman, Michael J, Fremont, Daved H, Curiel, David T, Diamond, Michael S
Format: Journal Article
Language:English
Published: United States 01.10.2020
Subjects:
Adenoviridae - genetics
Administration, Intranasal
Animals
Antibodies, Neutralizing - blood
Antibodies, Viral - blood
Chlorocebus aethiops
Coronavirus Infections - immunology
Coronavirus Infections - pathology
Coronavirus Infections - prevention & control
COVID-19
COVID-19 Vaccines
Female
HEK293 Cells
Humans
Immunogenicity, Vaccine
Injections, Intramuscular
Mice
Mice, Inbred BALB C
Pandemics
Pneumonia, Viral - immunology
Pneumonia, Viral - pathology
Respiratory Mucosa - immunology
Respiratory Mucosa - pathology
Respiratory Mucosa - virology
Spike Glycoprotein, Coronavirus - genetics
Spike Glycoprotein, Coronavirus - immunology
Vero Cells
Viral Vaccines - administration & dosage
Viral Vaccines - immunology
COVID-19
pathogenesis
IgA
SARS-CoV-2
vaccine
antibody
intranasal
protection
T cells
mucosal immunity
ISSN:1097-4172, 1097-4172
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Summary: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.
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ISSN:1097-4172
1097-4172
DOI:10.1016/j.cell.2020.08.026