Pharmacological Prevention of Severe Respiratory Syncytial Virus Infection in High-Risk Infants and Children: Maternal Immunization and Long-Acting Monoclonal Antibodies

Abstract

Respiratory syncytial virus (RSV) remains a major cause of lower respiratory tract disease and hospitalization in infants, with the highest burden concentrated during the first months of life and among children with limited cardiopulmonary reserve. Prevention has shifted from selective, repeatedly administered palivizumab to maternal RSV prefusion F protein vaccination and extended-half-life monoclonal antibodies. This review examines the pharmacological basis, clinical efficacy, safety, pharmacokinetics, real-world effectiveness, resistance, and implementation of these approaches, with emphasis on infants at increased risk of severe disease. Maternal RSVpreF vaccination raises maternal neutralizing antibodies and transfers IgG across the placenta, protecting the newborn. Nirsevimab and clesrovimab provide direct passive immunity and maintain antibody exposure through much of the first RSV season after a single dose. Randomized trials show substantial reductions in medically attended RSV lower respiratory tract disease and hospitalization with nirsevimab, while clesrovimab has demonstrated similar short-term clinical protection. Real-world studies from Europe, North America, and South America broadly confirm these benefits, although effectiveness varies with timing, coverage, endpoint definition, and epidemiology. Maternal vaccination has also shown protection against infant hospitalization in post-licensure studies. Important uncertainties include waning protection, breakthrough infection, resistance, second-season prevention, access, and the optimal use of maternal vaccination and infant monoclonal antibodies within the same health system. Prevention programs should therefore integrate product characteristics with gestational age, maternal vaccination status, infant age, medical risk, seasonality, and local delivery capacity.