Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials

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dc.contributor.authorMadhi, Shabir A.
dc.contributor.authorAhani, Bahar
dc.contributor.authorTuffy, Kevin M.
dc.contributor.authorAksyuk, Anastasia A.
dc.contributor.authorWilkins, Deidre
dc.contributor.authorAbram, Michael E.
dc.contributor.authorDagan, Ron
dc.contributor.authorDomachowske, Joseph B.
dc.contributor.authorGuest, Johnathan D.
dc.contributor.authorJi, Hong
dc.contributor.authorKushnir, Anna
dc.contributor.authorLeach, Amanda
dc.contributor.authorMankad, Vaishali S.
dc.contributor.authorSimões, Eric A. F.
dc.contributor.authorSparklin, Benjamin
dc.contributor.authorSpeer, Scott D.
dc.contributor.authorStanley, Ann Marie
dc.contributor.authorTabor, David E.
dc.contributor.authorHamrén, Ulrika Wählby
dc.contributor.authorKelly, Elizabeth J.
dc.contributor.authorVillafana, Tonya
dc.date.accessioned2024-11-23T14:01:50Z
dc.date.available2024-11-23T14:01:50Z
dc.date.issued2023
dc.description.abstractNirsevimab is a monoclonal antibody that binds to the respiratory syncytial virus (RSV) fusion protein. During the Phase 2b (NCT02878330) and MELODY (NCT03979313) clinical trials, infants received one dose of nirsevimab or placebo before their first RSV season. In this pre-specified analysis, isolates from RSV infections were subtyped, sequenced and analyzed for nirsevimab binding site substitutions; subsequently, recombinant RSVs were engineered for microneutralization susceptibility testing. Here we show that the frequency of infections caused by subtypes A and B is similar across and within the two trials. In addition, RSV A had one and RSV B had 10 fusion protein substitutions occurring at >5% frequency. Notably, RSV B binding site substitutions were rare, except for the highly prevalent I206M:Q209R, which increases nirsevimab susceptibility; RSV B isolates from two participants had binding site substitutions that reduce nirsevimab susceptibility. Overall, >99% of isolates from the Phase 2b and MELODY trials retained susceptibility to nirsevimab.
dc.description.submitterPM2024
dc.facultyFaculty of Health Sciences
dc.identifier0000-0002-7629-0636
dc.identifier.citationAhani, B., Tuffy, K.M., Aksyuk, A.A. et al. Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials. Nat Commun 14, 4347 (2023). https://doi.org/10.1038/s41467-023-40057-8
dc.identifier.issn2041-1723 (online)
dc.identifier.other10.1038/s41467-023-40057-8
dc.identifier.urihttps://hdl.handle.net/10539/42854
dc.journal.titleNature communications
dc.language.isoen
dc.publisherNature Research
dc.rights© The Author(s) 2023, corrected publication 2024.
dc.schoolSchool of Clinical Medicine
dc.subjectAntibodies
dc.subjectBiological therapy
dc.subjectPaediatric research
dc.subjectViral infection
dc.subject.otherSDG-3: Good health and well-being
dc.titleMolecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials
dc.typeArticle
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