A safe and effective mucosal RSV vaccine in mice consisting of RSV phosphoprotein and flagellin variant
Bali Zhao, Jingyi Yang, Bing He, Xian Li, Hu Yan, Shuning Liu, Yi Yang, Dihan Zhou, Bowen Liu, Xuxu Fan, Maohua Zhong, Ejuan Zhang, Fan Zhang, Yue Zhang, Yao-Qing Chen, Shibo Jiang, Huimin Yan, Huimin Yan, Huimin Yan
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 + T cells 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.