{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T17:11:02Z","timestamp":1793293862405,"version":"4.5.0"},"reference-count":52,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NextGenerationEU-MUR","award":["I83C22001810007"],"award-info":[{"award-number":["I83C22001810007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: Respiratory syncytial virus (RSV) remains a leading cause of lower respiratory tract infections and hospitalizations in infants and young children globally. Recently, RSV prevention has advanced with the introduction of nirsevimab, a long-acting monoclonal antibody, and the RSV preF vaccine for maternal immunization. While these interventions have improved early protection, several limitations hinder their broader impact and long-term effectiveness. Methods: This narrative review synthesizes evidence from clinical trials, observational studies, and regulatory reports to evaluate the main limitations of nirsevimab and maternal RSV vaccination. Literature searches were conducted in major databases, focusing on efficacy, safety, immunogenicity, implementation, and population-specific challenges. Results: Both nirsevimab and maternal vaccination provide strong protection during the first six months of life, but their effectiveness wanes thereafter. This is concerning as nearly half of RSV-related deaths occur in children over six months old. Maternal vaccine efficacy is uncertain in very-preterm infants, and safety concerns persist, including potential associations with preterm birth, Guillain\u2013Barr\u00e9 syndrome, and hypertensive disorders. Real-world data from low-income countries are lacking, limiting generalizability. Additionally, the risk of vaccine-associated enhanced disease (VAED), although unconfirmed, has delayed pediatric vaccine development. Emerging monoclonal antibodies and live-attenuated vaccines are under investigation to extend protection beyond infancy. Conclusions: Despite substantial progress, current RSV prevention strategies leave critical gaps, particularly for older infants and underserved populations. There is a pressing need for next-generation vaccines, enhanced pharmacovigilance, and equitable global implementation to ensure sustained and inclusive RSV protection.<\/jats:p>","DOI":"10.3390\/vaccines13070717","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T07:42:06Z","timestamp":1751355726000},"page":"717","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Challenges and Limitations of Current RSV Prevention Strategies in Infants and Young Children: A Narrative Review"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3468-5568","authenticated-orcid":false,"given":"Nicola","family":"Principi","sequence":"first","affiliation":[{"name":"Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5478-5657","authenticated-orcid":false,"given":"Serafina","family":"Perrone","sequence":"additional","affiliation":[{"name":"Neonatology Unit, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4103-2837","authenticated-orcid":false,"given":"Susanna","family":"Esposito","sequence":"additional","affiliation":[{"name":"Neonatology Unit, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"},{"name":"Pediatric Clinic, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e03074-24","DOI":"10.1128\/mbio.03074-24","article-title":"The Story behind the Science: On the discovery of respiratory syncytial virus","volume":"16","author":"Casadevall","year":"2025","journal-title":"mBio"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1080\/14656566.2025.2495091","article-title":"Past, present and future of respiratory syncytial infection prevention in infants and young children","volume":"26","author":"Esposito","year":"2025","journal-title":"Expert Opin. 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