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

Autor: Yixuan J. Hou, Ahmed O. Hassan, Haiyan Zhao, Michael J. Holtzman, Ian B. Harvey, Elena A. Kashentseva, David T. Curiel, Swathi Shrihari, Rita E. Chen, Alexandra Schäfer, Arthur S. Kim, Jonathan E. Danis, Brittany K. Smith, Michael S. Diamond, Daved H. Fremont, Ya Nan Dai, Adam L. Bailey, Daniela Weiskopf, Broc T. McCune, James Brett Case, Alex W. Wessel, Emma S. Winkler, Laura A. VanBlargan, Lisa E. Gralinski, Lucas J. Adams, Igor P. Dmitriev, Natasha M. Kafai, Ralph S. Baric, Meisheng Ma, Julie M. Fox, Shamus P. Keeler
Rok vydání: 2020
Předmět:
Immunoglobulin A
COVID-19 Vaccines
viruses
Pneumonia
Viral
Inflammation
Respiratory Mucosa
Biology
Antibodies
Viral
Injections
Intramuscular
Article
General Biochemistry
Genetics and Molecular Biology
Adenoviridae
03 medical and health sciences
Mice
0302 clinical medicine
Immune system
Immunogenicity
Vaccine
Immunity
Chlorocebus aethiops
medicine
Animals
Humans
Respiratory system
skin and connective tissue diseases
Pandemics
Vero Cells
Administration
Intranasal
030304 developmental biology
0303 health sciences
Mice
Inbred BALB C
Viral Vaccine
fungi
virus diseases
COVID-19
Viral Vaccines
Antibodies
Neutralizing
body regions
HEK293 Cells
Immunology
Spike Glycoprotein
Coronavirus
biology.protein
Nasal administration
Female
Antibody
medicine.symptom
Coronavirus Infections
030217 neurology & neurosurgery
Zdroj: Cell
ISSN: 1097-4172
Popis: 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 pre-fusion 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 IgA and T cell responses, and virtually completely 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.
Highlights • Chimpanzee adenoviral vaccines encoding stabilized S induce neutralizing Abs • Chimpanzee adenoviral vaccines protect against SARS-CoV-2 infection and pneumonia • Intranasal vaccine delivery generates robust mucosal B and T cell responses • Intranasal ChAd-SARS-CoV-2 prevents upper and low respiratory tract infection
Intranasal or intramuscular immunization of ChAd-SARS-CoV-2, a chimpanzee adenoviral vaccine encoding stabilized spike intramuscular prevents SARS-CoV-2 lung infection and pneumonia in mice. In particular, intranasally delivered ChAd-SARS-CoV-2 uniquely prevents both upper and lower respiratory tract infections, potentially protecting against SARS-CoV-2 infection and transmission.
Databáze: OpenAIRE
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