A single intranasal dose of human parainfluenza virus type 3-vectored vaccine induces effective antibody and memory T cell response in the lungs and protects hamsters against SARS-CoV-2

Respiratory tract vaccination has an advantage of needle-free delivery and induction of mucosal immune response in the portal of SARS-CoV-2 entry. We utilized human parainfluenza virus type 3 vector to generate constructs expressing the full spike (S) protein of SARS-CoV-2, its S1 subunit, or the re...

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Veröffentlicht in:npj vaccines Jg. 7; H. 1; S. 47 - 16
Hauptverfasser: Ilinykh, Philipp A., Periasamy, Sivakumar, Huang, Kai, Kuzmina, Natalia A., Ramanathan, Palaniappan, Meyer, Michelle N., Mire, Chad E., Kuzmin, Ivan V., Bharaj, Preeti, Endsley, Jessica R., Chikina, Maria, Sealfon, Stuart C., Widen, Steven G., Endsley, Mark A., Bukreyev, Alexander
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 25.04.2022
Nature Publishing Group
Nature Portfolio
Schlagworte:
631/250/255/2514
631/250/590/1867
631/326/596/4130
692/420/256/2516
Antibodies
Biomedical and Life Sciences
Biomedicine
COVID-19
COVID-19 vaccines
Immune response
Infectious Diseases
Influenza
Medical Microbiology
Protected animals
Proteins
Public Health
Respiratory tract
Rodents
Severe acute respiratory syndrome coronavirus 2
Vaccine
Vaccines
Virology
ISSN:2059-0105, 2059-0105
Online-Zugang:Volltext
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Zusammenfassung:Respiratory tract vaccination has an advantage of needle-free delivery and induction of mucosal immune response in the portal of SARS-CoV-2 entry. We utilized human parainfluenza virus type 3 vector to generate constructs expressing the full spike (S) protein of SARS-CoV-2, its S1 subunit, or the receptor-binding domain, and tested them in hamsters as single-dose intranasal vaccines. The construct bearing full-length S induced high titers of neutralizing antibodies specific to S protein domains critical to the protein functions. Robust memory T cell responses in the lungs were also induced, which represent an additional barrier to infection and should be less sensitive than the antibody responses to mutations present in SARS-CoV-2 variants. Following SARS-CoV-2 challenge, animals were protected from the disease and detectable viral replication. Vaccination prevented induction of gene pathways associated with inflammation. These results indicate advantages of respiratory vaccination against COVID-19 and inform the design of mucosal SARS-CoV-2 vaccines.
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ISSN:2059-0105
2059-0105
DOI:10.1038/s41541-022-00471-3