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

Cell Rep. 2021 Jul 20;36(3):109401. doi: 10.1016/j.celrep.2021.109401.


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.

Keywords: CD4(+) T cells; P-KFD1; RSV vaccine; Th17; VED; scRNA-seq.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Line
  • Clone Cells
  • Cytotoxicity, Immunologic / genetics
  • Female
  • Flagellin / genetics*
  • Humans
  • Immunity
  • Immunity, Mucosal / immunology*
  • Immunization
  • Interferon-gamma / metabolism
  • Interleukin-17 / metabolism
  • Lung Diseases / pathology
  • Lung Diseases / virology
  • Lymphocyte Activation / immunology
  • Mice, Inbred BALB C
  • Mutation / genetics*
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Recombinant Proteins / immunology
  • Respiratory Syncytial Virus Vaccines / adverse effects*
  • Respiratory Syncytial Virus Vaccines / immunology*
  • Respiratory Syncytial Virus, Human / immunology*
  • Single-Cell Analysis
  • Th1 Cells / immunology
  • Th17 Cells / immunology


  • Antibodies, Viral
  • Interleukin-17
  • Phosphoproteins
  • Recombinant Proteins
  • Respiratory Syncytial Virus Vaccines
  • Flagellin
  • Interferon-gamma