{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:16:17Z","timestamp":1790363777560,"version":"4.1.0"},"reference-count":42,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T00:00:00Z","timestamp":1718236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AstraZeneca and Sanofi"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Background: Nirsevimab is approved in the US for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants during their first RSV season and in children aged \u226424 months who remain vulnerable to severe RSV disease through their second RSV season. We summarize a pre-specified analysis of nirsevimab safety data from three randomized controlled trials: Phase 2b (NCT02878330; healthy infants born \u226529 to &lt;35 weeks\u2019 gestational age [wGA]); Phase 3 MELODY (NCT03979313; healthy infants born \u226535 wGA); and Phase 2\/3 MEDLEY (NCT03959488; infants with congenital heart disease [CHD] and\/or chronic lung disease of prematurity [CLD] or born \u226435 wGA). Methods: Participants (randomized 2:1) received a single intramuscular dose of nirsevimab or comparator (placebo, Phase 2b\/MELODY; 5\u00d7 once-monthly palivizumab, MEDLEY) before their first RSV season (recipients &lt; 5 kg, nirsevimab 50 mg; \u22655 kg, nirsevimab 100 mg). In MEDLEY, children with CHD\/CLD continued to a second RSV season: first-season nirsevimab recipients received nirsevimab 200 mg; first-season palivizumab recipients were re-randomized 1:1 to receive nirsevimab 200 mg or 5\u00d7 once-monthly palivizumab. Results: The incidence, severity, and nature of AEs were similar across treatments (nirsevimab, n = 3184; placebo, n = 1284; palivizumab, n = 304). Most AEs were mild to moderate in severity, with \u226598% unrelated to treatment. AEs of special interest occurred infrequently (&lt;1%): no anaphylaxis or thrombocytopenia were treatment-related, and no immune complex disease was reported. Deaths (incidence &lt; 1.0%) were all unrelated to treatment. Conclusions: A single dose per season of nirsevimab for the prevention of RSV disease had a favorable safety profile, irrespective of wGA or comorbidities.<\/jats:p>","DOI":"10.3390\/pathogens13060503","type":"journal-article","created":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T06:23:11Z","timestamp":1718259791000},"page":"503","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Comprehensive Summary of Safety Data on Nirsevimab in Infants and Children from All Pivotal Randomized Clinical Trials"],"prefix":"10.3390","volume":"13","author":[{"given":"Vaishali S.","family":"Mankad","sequence":"first","affiliation":[{"name":"Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Durham, NC 27703, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Leach","sequence":"additional","affiliation":[{"name":"Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7835-8552","authenticated-orcid":false,"given":"Yue","family":"Chang","sequence":"additional","affiliation":[{"name":"Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrika","family":"W\u00e4hlby Hamr\u00e9n","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology, R&D, AstraZeneca, SE-43183 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Kiazand","sequence":"additional","affiliation":[{"name":"Patient Safety, Chief Medical Office, Oncology R&D, AstraZeneca, Gaithersburg, MD 20878, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Kubiak","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Therese","family":"Takas","sequence":"additional","affiliation":[{"name":"Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tonya","family":"Villafana","sequence":"additional","affiliation":[{"name":"Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7879-1041","authenticated-orcid":false,"given":"Manish","family":"Shroff","sequence":"additional","affiliation":[{"name":"Patient Safety, Chief Medical Office, Oncology R&D, AstraZeneca, Waltham, MA 02451, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1016\/S0140-6736(22)00478-0","article-title":"Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: A systematic analysis","volume":"399","author":"Li","year":"2022","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"92","DOI":"10.2174\/187152612800100099","article-title":"The burgeoning burden of respiratory syncytial virus among children","volume":"12","author":"Hall","year":"2012","journal-title":"Infect. Disord. Drug Targets"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e341","DOI":"10.1542\/peds.2013-0303","article-title":"Respiratory syncytial virus-associated hospitalizations among children less than 24 months of age","volume":"132","author":"Hall","year":"2013","journal-title":"Pediatrics"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1080\/14760584.2017.1333425","article-title":"Passive and active immunization against respiratory syncytial virus for the young and old","volume":"16","author":"Villafana","year":"2017","journal-title":"Expert Rev. Vaccines"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1093\/oxfordjournals.aje.a120955","article-title":"Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine","volume":"89","author":"Kim","year":"1969","journal-title":"Am. J. Epidemiol."},{"key":"ref_6","unstructured":"AstraZeneca, A.B. (2024, February 20). Synagis (Palivizumab) US Prescribing Information. Available online: https:\/\/synagishcp.com\/synagis.pdf."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"The PREVENT Study Group (1997). Reduction of respiratory syncytial virus hospitalization among premature infants and infants with bronchopulmonary dysplasia using respiratory syncytial virus immune globulin prophylaxis. Pediatrics, 99, 93\u201399.","DOI":"10.1542\/peds.99.1.93"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/S0022-3476(98)70056-3","article-title":"Respiratory syncytial virus immune globulin for prophylaxis against respiratory syncytial virus disease in infants and children with congenital heart disease. The Cardiac Study Group","volume":"133","author":"Simoes","year":"1998","journal-title":"J. Pediatr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S620","DOI":"10.1093\/infdis\/jiz492","article-title":"for the RESCEU Investigators Respiratory syncytial virus-associated acute lower respiratory infections in children with bronchopulmonary dysplasia: Systematic review and meta-analysis","volume":"222","author":"Chaw","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S613","DOI":"10.1093\/infdis\/jiz150","article-title":"Acute lower respiratory infections associated with respiratory syncytial virus in children with underlying congenital heart disease: Systematic review and meta-analysis","volume":"222","author":"Chaw","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"eaaj1928","DOI":"10.1126\/scitranslmed.aaj1928","article-title":"A highly potent extended half-life antibody as a potential RSV vaccine surrogate for all infants","volume":"9","author":"Zhu","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"309ra162","DOI":"10.1126\/scitranslmed.aac4241","article-title":"Prefusion F-specific antibodies determine the magnitude of RSV neutralizing activity in human sera","volume":"7","author":"Ngwuta","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e01714-16","DOI":"10.1128\/AAC.01714-16","article-title":"Safety, tolerability, and pharmacokinetics of MEDI8897, the respiratory syncytial virus prefusion F-targeting monoclonal antibody with an extended half-life, in healthy adults","volume":"61","author":"Griffin","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"422","DOI":"10.4161\/mabs.3.5.16983","article-title":"Neonatal Fc receptor and IgG-based therapeutics","volume":"3","author":"Kuo","year":"2011","journal-title":"MAbs"},{"key":"ref_15","first-page":"634","article-title":"The half-lives of IgG subclasses and specific antibodies in patients with primary immunodeficiency who are receiving intravenously administered immunoglobulin","volume":"112","author":"Mankarious","year":"1988","journal-title":"J. Lab. Clin. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1056\/NEJMoa2110275","article-title":"Nirsevimab for prevention of RSV in healthy late-preterm and term infants","volume":"386","author":"Hammitt","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"23514","DOI":"10.1074\/jbc.M604292200","article-title":"Properties of human IgG1s engineered for enhanced binding to the neonatal Fc receptor (FcRn)","volume":"281","author":"Kiener","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1056\/NEJMoa1913556","article-title":"Single-dose nirsevimab for prevention of RSV in preterm infants","volume":"383","author":"Griffin","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1056\/NEJMc2214773","article-title":"Nirsevimab for prevention of RSV in term and late-preterm infants","volume":"388","author":"Muller","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1056\/NEJMc2112186","article-title":"Safety of nirsevimab for RSV in infants with heart or lung disease or prematurity","volume":"386","author":"Domachowske","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1093\/jpids\/piad052","article-title":"Safety of re-dosing nirsevimab prior to RSV season 2 in children with heart or lung disease","volume":"12","author":"Domachowske","year":"2023","journal-title":"J. Pediatric Infect. Dis. Soc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/S2352-4642(22)00321-2","article-title":"Efficacy of nirsevimab against respiratory syncytial virus lower respiratory tract infections in preterm and term infants, and pharmacokinetic extrapolation to infants with congenital heart disease and chronic lung disease: A pooled analysis of randomised controlled trials","volume":"7","author":"Madhi","year":"2023","journal-title":"Lancet Child. Adolesc. Health"},{"key":"ref_23","unstructured":"Sanofi (2024, February 20). BeyfortusTM (Nirsevimab-Alip) FDA Prescribing Information. 18 July 2023. Available online: https:\/\/products.sanofi.us\/beyfortus\/beyfortus.pdf."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s40121-014-0046-6","article-title":"Safety and effectiveness of palivizumab in children at high risk of serious disease due to respiratory syncytial virus infection: A Systematic Review","volume":"3","author":"Wegzyn","year":"2014","journal-title":"Infect. Dis. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"The IMpact-RSV Study Group (1998). Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. The IMpact-RSV Study Group. Pediatrics, 102, 531\u2013537.","DOI":"10.1542\/peds.102.3.531"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1067\/S0022-3476(03)00454-2","article-title":"Palivizumab prophylaxis reduces hospitalization due to respiratory syncytial virus in young children with hemodynamically significant congenital heart disease","volume":"143","author":"Feltes","year":"2003","journal-title":"J. Pediatr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nrd3003","article-title":"The safety and side effects of monoclonal antibodies","volume":"9","author":"Hansel","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e35","DOI":"10.1542\/peds.2008-1036","article-title":"Motavizumab for prophylaxis of respiratory syncytial virus in high-risk children: A noninferiority trial","volume":"125","author":"Dagan","year":"2010","journal-title":"Pediatrics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1203\/PDR.0b013e318220a553","article-title":"on behalf of Motavizumab Cardiac Study Group. A randomized controlled trial of motavizumab versus palivizumab for the prophylaxis of serious respiratory syncytial virus disease in children with hemodynamically significant congenital heart disease","volume":"70","author":"Feltes","year":"2011","journal-title":"Pediatr. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/ijlh.14075","article-title":"Platelet factor 4 triggers thrombo-inflammation by bridging innate and adaptive immunity","volume":"45","author":"Greinacher","year":"2023","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/ejh.13549","article-title":"Current understanding and future implications of sepsis-induced thrombocytopenia","volume":"106","author":"Ghimire","year":"2021","journal-title":"Eur. J. Haematol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1111\/j.1442-200X.1998.tb01928.x","article-title":"Five cases of thrombocytopenia induced by primary human herpesvirus 6 infection","volume":"40","author":"Yoshikawa","year":"1998","journal-title":"Acta Paediatr. Jpn."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/s41541-019-0132-6","article-title":"The how\u2019s and what\u2019s of vaccine reactogenicity","volume":"4","author":"Didierlaurent","year":"2019","journal-title":"NPJ Vaccines"},{"key":"ref_34","unstructured":"GlaxoSmithKline (2024, February 20). INFANRIX (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed) US Prescribing Information, Available online: https:\/\/www.fda.gov\/media\/75157\/download."},{"key":"ref_35","unstructured":"Wyeth Pharmaceuticals (2024, February 20). PREVNAR 13 (Pneumococcal 13-Valent Conjugate Vaccine [Diphtheria CRM197 Protein]), Available online: https:\/\/www.fda.gov\/files\/vaccines%2C%20blood%20%26%20biologics\/published\/Package-Insert------Prevnar-13.pdf."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"708939","DOI":"10.3389\/fimmu.2021.708939","article-title":"Coadministration of anti-viral monoclonal antibodies with routine pediatric vaccines and implications for nirsevimab use: A White Paper","volume":"12","author":"Esposito","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/nm.1894","article-title":"Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease","volume":"15","author":"Delgado","year":"2009","journal-title":"Nat. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1128\/jcm.26.8.1595-1597.1988","article-title":"Formalin-inactivated respiratory syncytial virus vaccine induces antibodies to the fusion glycoprotein that are deficient in fusion-inhibiting activity","volume":"26","author":"Murphy","year":"1988","journal-title":"J. Clin. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1084\/jem.20020781","article-title":"A role for immune complexes in enhanced respiratory syncytial virus disease","volume":"196","author":"Polack","year":"2002","journal-title":"J. Exp. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1038\/s41591-023-02316-5","article-title":"Durability of neutralizing RSV antibodies following nirsevimab administration and elicitation of the natural immune response to RSV infection in infants","volume":"29","author":"Wilkins","year":"2023","journal-title":"Nat. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1093\/jpids\/piad113","article-title":"Infants Receiving a single dose of nirsevimab to prevent RSV do not have evidence of enhanced disease in their second RSV season","volume":"13","author":"Dagan","year":"2024","journal-title":"J. Pediatric Infect. Dis. Soc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1056\/NEJMoa2309189","article-title":"Nirsevimab for prevention of hospitalizations due to RSV in infants","volume":"389","author":"Drysdale","year":"2023","journal-title":"N. Engl. J. Med."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/13\/6\/503\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:57:52Z","timestamp":1760108272000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/13\/6\/503"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,13]]},"references-count":42,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["pathogens13060503"],"URL":"https:\/\/doi.org\/10.3390\/pathogens13060503","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,13]]}}}