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
Affiliations
Philipp A. Ilinykh
Department of Pathology, University of Texas Medical Branch
Sivakumar Periasamy
Department of Pathology, University of Texas Medical Branch
Kai Huang
Department of Pathology, University of Texas Medical Branch
Natalia A. Kuzmina
Department of Pathology, University of Texas Medical Branch
Palaniappan Ramanathan
Department of Pathology, University of Texas Medical Branch
Michelle N. Meyer
Department of Pathology, University of Texas Medical Branch
Chad E. Mire
Department of Microbiology and Immunology, University of Texas Medical Branch
Ivan V. Kuzmin
Department of Pathology, University of Texas Medical Branch
Preeti Bharaj
Department of Pathology, University of Texas Medical Branch
Jessica R. Endsley
Department of Microbiology and Immunology, University of Texas Medical Branch
Maria Chikina
Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh
Stuart C. Sealfon
Department of Neurology, Icahn School of Medicine at Mount Sinai
Steven G. Widen
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch
Mark A. Endsley
Department of Microbiology and Immunology, University of Texas Medical Branch
Alexander Bukreyev
Department of Pathology, University of Texas Medical Branch
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.
