A Safe and Effective Mucosal RSV Vaccine Consisting of RSV Phosphoprotein and Flagellin Variant

SUMMARYRespiratory syncytial virus (RSV) is a major cause of serious acute lower respiratory tract infection in infants and the elderly. No licensed RSV vaccine available thus far calls for the development of vaccines with new target(s) and vaccination strategies. Here, we constructed a recombinant protein, designated P-KFD1, comprised of RSV phosphoprotein (P) and E. coli K12 strain-derived flagellin variant KFD1. Intranasal (i.n.) immunization with P-KFD1 inhibits RSV replication in both 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 i.n. immunization, either reside in or migrate to respiratory tract, mediate protection against RSV infection. Sc-RNA seq and carboxyfluorescein succinimidyl ester (CFSE) labeled cell transfer further characterized the Th1 and Th17 responses induced by P-KFD1. Finally, we found the anti-viral protection depends on either IFN-γ or IL-17A. Collectively, P-KFD1 is promising as a safe and effective mucosal vaccine candidate to prevent RSV infection.HIGHLIGHTSA new subunit RSV vaccine candidate with new target and vaccination strategy, P-KFD1, is designed and generatedIntranasal immunization with P-KFD1 protects mice against RSV infection and averts vaccine-enhanced diseaseSc-RNA seq and CFSE-labelled cell transfer identified characteristics of the protective CD4+ T cellsLocal and peripheral CD4+ T cells provide protection against RSV infection dependent on either IFN-γ or IL-17A