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

doi:10.1016/j.isci.2021.103379

Non-propagative human parainfluenza virus type 2 nasal vaccine robustly protects the upper and lower airways against SARS-CoV-2

iScience. 2021 Dec 17;24(12):103379. doi: 10.1016/j.isci.2021.103379. Epub 2021 Nov 17.

Authors

Junpei Ohtsuka^{1

2

3}, Masaki Imai⁴, Masayuki Fukumura^{1

2

3}, Mitsuyo Maeda^{5

6}, Asami Eguchi^{5

6}, Ryoichi Ono¹, Tadashi Maemura^{4

7}, Mutsumi Ito⁴, Seiya Yamayoshi⁴, Yosky Kataoka^{5

6}, Yoshihiro Kawaoka^{4

7

8}, Tetsuya Nosaka^{1

2}

Affiliations

¹ Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine, Tsu 514-8507, Japan.
² Research Center for Development of Recombinant VLP Vaccines, Research Institutes of Excellence, Mie University, Tsu 514-8507, Japan.
³ BioComo Inc., Komono, Mie 510-1233, Japan.
⁴ Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
⁵ Multi-Modal Microstructure Analysis Unit, RIKEN-JEOL Collaboration Center, Kobe 650-0047, Japan.
⁶ Laboratory for Cellular Function Imaging, RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, Japan.
⁷ Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA.
⁸ Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.

Abstract

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.

Keywords: Infection control in health technology; Virology.