Non-propagative human parainfluenza virus type 2 nasal vaccine robustly protects the upper and lower airways against SARS-CoV-2
Junpei Ohtsuka,
Masaki Imai,
Masayuki Fukumura,
Mitsuyo Maeda,
Asami Eguchi,
Ryoichi Ono,
Tadashi Maemura,
Mutsumi Ito,
Seiya Yamayoshi,
Yosky Kataoka,
Yoshihiro Kawaoka,
Tetsuya Nosaka
Affiliations
Junpei Ohtsuka
Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine, Tsu 514-8507, Japan; Research Center for Development of Recombinant VLP Vaccines, Research Institutes of Excellence, Mie University, Tsu 514-8507, Japan; BioComo Inc., Komono, Mie 510-1233, Japan
Masaki Imai
Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
Masayuki Fukumura
Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine, Tsu 514-8507, Japan; Research Center for Development of Recombinant VLP Vaccines, Research Institutes of Excellence, Mie University, Tsu 514-8507, Japan; BioComo Inc., Komono, Mie 510-1233, Japan; Corresponding author
Mitsuyo Maeda
Multi-Modal Microstructure Analysis Unit, RIKEN-JEOL Collaboration Center, Kobe 650-0047, Japan; Laboratory for Cellular Function Imaging, RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan
Asami Eguchi
Multi-Modal Microstructure Analysis Unit, RIKEN-JEOL Collaboration Center, Kobe 650-0047, Japan; Laboratory for Cellular Function Imaging, RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan
Ryoichi Ono
Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine, Tsu 514-8507, Japan
Tadashi Maemura
Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA
Mutsumi Ito
Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
Seiya Yamayoshi
Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
Yosky Kataoka
Multi-Modal Microstructure Analysis Unit, RIKEN-JEOL Collaboration Center, Kobe 650-0047, Japan; Laboratory for Cellular Function Imaging, RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan
Yoshihiro Kawaoka
Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA; Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
Tetsuya Nosaka
Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine, Tsu 514-8507, Japan; Research Center for Development of Recombinant VLP Vaccines, Research Institutes of Excellence, Mie University, Tsu 514-8507, Japan; Corresponding author
Summary: We developed an intranasal vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using the replication-incompetent human parainfluenza virus type 2 (hPIV2) vector BC-PIV, which can deliver ectopic gene as stable RNA and ectopic protein on the envelope. BC-PIV expressing the full-length prefusion-stabilized spike gene (K986P/V987P) of SARS-CoV-2, S-2PM, possessed a corona-like viral envelope. Intranasal vaccination of mice with BC-PIV/S-2PM induced high levels of neutralizing immunoglobulin G (IgG) and mucosal IgA antibodies against the spike protein. Although BC-PIV showed hemagglutinating activity, BC-PIV/S-2PM lacked such activity, in accordance with the presence of the massive spike protein on the viral surface. Furthermore, single-dose intranasal vaccination of hamsters with BC-PIV/S-2PM completely protected the lungs from SARS-CoV-2 at 11-week post-immunization, and boost vaccination two weeks before the challenge conferred virtually complete protection of the nasal turbinates against SARS-CoV-2. Thus, this chimeric hPIV2/spike intranasal vaccine is a promising vaccine candidate for SARS-CoV-2 to curtail virus transmission.
