A novel RSV F-Fc fusion protein vaccine reduces lung injury induced by respiratory syncytial virus infection

Abstract Respiratory syncytial virus (RSV) infection causes significant disease in the lower respiratory tract of young children, and there is currently no licensed vaccine to prevent RSV infection. The F glycoprotein is considered a major antigenic target for RSV vaccine development. Recent evidence indicates that the pre-fusion F state, compared with the post-fusion F state, is a superior antigen for generation of neutralizing antibodies. In this study, we developed a novel vaccine antigen, RSV glycoprotein F fused with an IgG Fc fragment (F-Fc). The F-Fc fusion protein is predominantly a hexamer and could be recognized by the pre-fusion F-specific monoclonal antibody D25. Intranasal immunization with the F-Fc fusion protein promoted a protective Th1-biased cellular immune response relative to that promoted by immunization with the F protein. This immunization strategy significantly reduced the lung viral load in mice. Furthermore, immunization with F-Fc reduced lung pathology and the production of pro-inflammatory cytokines and chemokines in the lung after RSV infection. These results suggest that the F-Fc protein may be a safe and effective RSV vaccine candidate.