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

Abstract

Respiratory syncytial virus, 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 post-fusion 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 which 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.

Importance

RSV, as an endemic virus infection, does not itself represent a pandemic threat. Since respiratory viruses have caused several pandemics, claiming millions of lives, the lessons learned from RSV research might contribute to pandemic preparedness.

Accepted manuscripts

Accepted manuscripts are PDF versions of the author’s final manuscript, as accepted for publication by the journal but prior to copyediting or typesetting. They can be cited using the author(s), article title, journal title, year of online publication, and DOI. They will be replaced by the final typeset articles, which may therefore contain changes. The DOI will remain the same throughout.