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

Philipp A. Ilinykh, Sivakumar Periasamy, Kai Huang, Natalia A. Kuzmina, Palaniappan Ramanathan, Michelle Meyer, Chad Mire, Ivan V. Kuzmin, Preeti Bharaj, Jessica R. Endsley, Maria Chikina, Stuart C. Sealfon, Steven Widen, Mark A. Endsley, Alexander Bukreyev

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number47
Journalnpj Vaccines
Volume7
Issue number1
DOIs
StatePublished - Dec 2022

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Infectious Diseases
  • Pharmacology (medical)

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