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

Abstract

SummaryWe 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.

Highlights

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a serious threat to people around the world by causing coronavirus disease 2019 (COVID-19)
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 vector BC-PIV, which can deliver ectopic gene as stable RNA and ectopic protein on the envelope
Intranasal vaccination of mice with BCPIV/S-2PM induced high levels of neutralizing immunoglobulin G (IgG) and mucosal IgA antibodies against the spike protein

Summary

Introduction

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a serious threat to people around the world by causing coronavirus disease 2019 (COVID-19). Once SARS-CoV-2 reaches the lungs, it causes severe pneumonia in combination with cytokine release syndrome and/or microvascular disease (Cyranoski, 2020; Zhou et al, 2020; Zhu et al, 2020). A nasal vaccine is an ideal method of protecting against SARS-CoV-2 infection at the point of entry, the upper respiratory tract, by inducing mucosal-neutralizing IgA antibodies. To avoid the development of vaccine-associated enhanced respiratory disease (ERD) and antibody-dependent enhancement (ADE) (Graham, 2020), a steric structure-based vaccine design to induce efficiently neutralizing antibodies is mandatory, such events are not common in SARS-CoV-2 infection. To overcome COVID-19, a safe, efficacious, cost-effective, and easy-to-handle vaccine is crucial

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