RSV vaccine development: advances and fusion protein-focused strategies

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections, particularly affecting infants, young children, older adults, and immunocompromised individuals. While RSV infection often causes mild, cold-like symptoms, it can progress to severe pulmonary disease in these vulnerable populations, frequently necessitating hospitalization. Decades of research have defined the RSV fusion protein, particularly its prefusion form, as the primary target for prophylaxis and vaccine design. This has advanced transformative milestones, including the approval of long-acting monoclonal antibodies (Nirsevimab, Clesrovimab) and the vaccines for adults (Arexvy, Abrysvo, mRESVIA). This review begins with RSV molecular virology, summarizes the evolution of prophylactic antibody, and revisits lessons from past vaccine failures. It then emphasizes the current landscape of RSV vaccine development, categorizing platforms such as mRNA, protein subunit, virus-like particle/nanoparticle, live-attenuated, and viral vector approaches, highlighting both licensed vaccines and leading candidates under clinical evaluation. This review overviews current RSV vaccines and antibody prophylaxis and aims to inform the development of future prevention strategies.