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 N Meyer; Chad E Mire; Ivan V Kuzmin; Preeti Bharaj; Jessica R Endsley; Maria Chikina; Stuart C Sealfon; Steven G Widen; Mark A Endsley; Alexander Bukreyev

doi:10.1038/s41541-022-00471-3

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

NPJ Vaccines. 2022 Apr 25;7(1):47. doi: 10.1038/s41541-022-00471-3.

Authors

Philipp A Ilinykh^{1

2}, Sivakumar Periasamy^{1

2}, Kai Huang^{1

2}, Natalia A Kuzmina^{1

2}, Palaniappan Ramanathan^{1

2}, Michelle N Meyer^{1

2}, Chad E Mire³, Ivan V Kuzmin^{1

2}, Preeti Bharaj^{1

2}, Jessica R Endsley³, Maria Chikina⁴, Stuart C Sealfon⁵, Steven G Widen⁶, Mark A Endsley³, Alexander Bukreyev^{7

8

9}

Affiliations

¹ Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
² Galveston National Laboratory, Galveston, TX, USA.
³ Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
⁴ Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
⁵ Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁶ Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
⁷ Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA. alexander.bukreyev@utmb.edu.
⁸ Galveston National Laboratory, Galveston, TX, USA. alexander.bukreyev@utmb.edu.
⁹ Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA. alexander.bukreyev@utmb.edu.

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.

Grants and funding

N/A/University of Texas Medical Branch at Galveston | Institute for Translational Sciences, University of Texas Medical Branch (Institute for Translational Sciences at UTMB)