A safe and effective mucosal RSV vaccine in mice consisting of RSV phosphoprotein and flagellin variant.

Shibo Jiang,Yue Zhang,Bowen Liu,Dihan Zhou,Xuxu Fan,Shuning Liu,Maohua Zhong,Bing He,Bali Zhao,Xian Li,Ejuan Zhang,Yi Yang,Huimin Yan,Yao-Qing Chen,Hu Yan,Fan Zhang,Jingyi Yang

doi:10.1016/j.celrep.2021.109401

Abstract

Respiratory syncytial virus (RSV) is a major cause of serious acute lower respiratory tract infection in infants and the elderly. The lack of a licensed RSV vaccine calls for the development of vaccines with other targets and vaccination strategies. Here, we construct a recombinant protein, designated P-KFD1, comprising RSV phosphoprotein (P) and the E.-coli-K12-strain-derived flagellin variant KFD1. Intranasal immunization with P-KFD1 inhibits RSV replication in the upper and lower respiratory tract and protects mice against lung disease without vaccine-enhanced disease (VED). The P-specific CD4+ Tcells provoked by P-KFD1 intranasal (i.n.) immunization either reside in or migrate to the respiratory tract and mediate protection against RSV infection. Single-cell RNA sequencing (scRNA-seq) and carboxyfluorescein succinimidyl ester (CFSE)-labeled cell transfer further characterize the Th1 and Th17 responses induced by P-KFD1. Finally, we find that anti-viral protection depends on either interferon-γ (IFN-γ) or interleukin-17A (IL-17A). Collectively, P-KFD1 is a promising safe and effective mucosal vaccine candidate for the prevention of RSV infection.

Highlights

Human respiratory syncytial virus (RSV) was first isolated and identified as an important cause of bronchiolitis in infants as early as 1956 (Blount et al, 1956; Chanock and Finberg, 1957)
P-specific immune responses induced by i.n. immunization with P-KFD1 or P+cholera toxin B subunit (CTB) protect mice against Respiratory syncytial virus (RSV) infection We generated a recombinant protein, P-KFD1 (Figures S1A and S1B), and investigated the immunogenicity and anti-viral efficacy of P-KFD1 as a potential mucosal subunit RSV vaccine targeting P
High levels of P-specific saliva immunoglobulin A (IgA), serum IgG, and serum IgA antibody responses could be induced by i.n. immunization with either P-KFD1 or protein mixed with mg of CTB (P+CTB) compared to sham immunization (Figure 1C)

Summary

Introduction

Human respiratory syncytial virus (RSV) was first isolated and identified as an important cause of bronchiolitis in infants as early as 1956 (Blount et al, 1956; Chanock and Finberg, 1957). It remains a major cause of severe acute lower respiratory tract infection in infants and in young children, the elderly, and immunocompromised populations worldwide (Chemaly et al, 2014; Falsey et al, 2005; Nair et al, 2010). The development of a safe and effective RSV vaccine has been elusive far

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