Development of a genetically modified full-length human respiratory syncytial virus preF protein vaccine

Human Respiratory Syncytial Virus (hRSV) is a major cause of acute lower respiratory tract infections (ALRTI) in infants, the elderly, and immunocompromised individuals. The recent approval of recombinant protein-based hRSV vaccines represents significant progress in combating hRSV. However, these vaccines utilized optimized preF ectodomain attached with an exogenous trimeric motif, which may induce immunological complications. Our research addresses these concerns by employing modified "full-length" preF proteins, preF-TMCT, designed to mimic the natural F protein structure and avoid potential immunological complications. We characterized a group of preF constructs and identified two candidates that exhibited desirable expression levels, high antigenicity and good stability. Immunization of Balb/c mice confirmed the robust immunogenicity and effective in induction of cross-reactive neutralizing antibodies of these antigens, particularly the lead-construct BR40. This investigation aims to contribute new insights to hRSV vaccine development. The near-native structure of the "full-length" preF-TMCT antigen also makes it valuable for producing therapeutic monoclonal antibodies (mAbs) and other biopharmaceuticals against hRSV infection.