Respiratory syncytial virus: health burden, disease prevention, and treatment-recent progress and lessons learned.

Respiratory syncytial virus (RSV), a negative-sense single-stranded RNA virus of the Pneumoviridae family, represents the most important pathogen of lower respiratory tract infections in young infants causing yearly epidemics. RSV is also an important respiratory viral pathogen for older subjects, which is second only to seasonal influenza virus infections. RSV represents a substantial public health burden with respect to morbidity and mortality, particularly in developing countries. Prevention and treatment options would therefore lessen the global disease burden. A formalin-inactivated RSV vaccine in the 1960s induced an enhanced disease upon exposure to natural RSV. After this tragical vaccine failure, it took nearly five decades of intensive research before prevention tools were approved by health authorities. The lead was taken by passive immunity approaches with injected monoclonal antibodies directed against the fusion protein F of RSV. The elucidation of the three-dimensional structure of the F protein revealed pre- and postfusion conformations. Subsequently, structure-based antigen engineering of the F protein paved the way for development of a prophylactic vaccine. In 2023, RSV vaccines were approved for maternal vaccination to protect young infants by placental transfer of antibodies and for vaccination in older subjects. Antiviral drugs that target the RSV fusion process, the RSV replicase, or the cytoplasmic viral factories are in development. Important research papers leading to these developments are reviewed here.