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Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials
by
Mankad, Vaishali S.
, Sparklin, Benjamin
, Ahani, Bahar
, Stanley, Ann Marie
, Kushnir, Anna
, Ji, Hong
, Tuffy, Kevin M.
, Kelly, Elizabeth J.
, Wilkins, Deidre
, Aksyuk, Anastasia A.
, Hamrén, Ulrika Wählby
, Dagan, Ron
, Speer, Scott D.
, Domachowske, Joseph B.
, Guest, Johnathan D.
, Abram, Michael E.
, Simões, Eric A. F.
, Tabor, David E.
, Leach, Amanda
, Madhi, Shabir A.
, Villafana, Tonya
in
13
/ 13/1
/ 631/250/2152/2153/1291
/ 692/308/3187
/ 692/699/255/2514
/ 692/700/565/1331
/ 82/1
/ 82/81
/ Antibodies, Monoclonal, Humanized - therapeutic use
/ Binding sites
/ Clinical trials
/ Fusion protein
/ Humanities and Social Sciences
/ Humans
/ Infant
/ Infants
/ Infections
/ Monoclonal antibodies
/ multidisciplinary
/ Proteins
/ Recombinant Proteins - therapeutic use
/ Respiratory syncytial virus
/ Respiratory Syncytial Virus Infections - drug therapy
/ Respiratory Syncytial Virus Infections - epidemiology
/ Respiratory Syncytial Virus, Human
/ Science
/ Science (multidisciplinary)
/ Susceptibility
/ Viruses
2023
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Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials
by
Mankad, Vaishali S.
, Sparklin, Benjamin
, Ahani, Bahar
, Stanley, Ann Marie
, Kushnir, Anna
, Ji, Hong
, Tuffy, Kevin M.
, Kelly, Elizabeth J.
, Wilkins, Deidre
, Aksyuk, Anastasia A.
, Hamrén, Ulrika Wählby
, Dagan, Ron
, Speer, Scott D.
, Domachowske, Joseph B.
, Guest, Johnathan D.
, Abram, Michael E.
, Simões, Eric A. F.
, Tabor, David E.
, Leach, Amanda
, Madhi, Shabir A.
, Villafana, Tonya
in
13
/ 13/1
/ 631/250/2152/2153/1291
/ 692/308/3187
/ 692/699/255/2514
/ 692/700/565/1331
/ 82/1
/ 82/81
/ Antibodies, Monoclonal, Humanized - therapeutic use
/ Binding sites
/ Clinical trials
/ Fusion protein
/ Humanities and Social Sciences
/ Humans
/ Infant
/ Infants
/ Infections
/ Monoclonal antibodies
/ multidisciplinary
/ Proteins
/ Recombinant Proteins - therapeutic use
/ Respiratory syncytial virus
/ Respiratory Syncytial Virus Infections - drug therapy
/ Respiratory Syncytial Virus Infections - epidemiology
/ Respiratory Syncytial Virus, Human
/ Science
/ Science (multidisciplinary)
/ Susceptibility
/ Viruses
2023
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Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials
by
Mankad, Vaishali S.
, Sparklin, Benjamin
, Ahani, Bahar
, Stanley, Ann Marie
, Kushnir, Anna
, Ji, Hong
, Tuffy, Kevin M.
, Kelly, Elizabeth J.
, Wilkins, Deidre
, Aksyuk, Anastasia A.
, Hamrén, Ulrika Wählby
, Dagan, Ron
, Speer, Scott D.
, Domachowske, Joseph B.
, Guest, Johnathan D.
, Abram, Michael E.
, Simões, Eric A. F.
, Tabor, David E.
, Leach, Amanda
, Madhi, Shabir A.
, Villafana, Tonya
in
13
/ 13/1
/ 631/250/2152/2153/1291
/ 692/308/3187
/ 692/699/255/2514
/ 692/700/565/1331
/ 82/1
/ 82/81
/ Antibodies, Monoclonal, Humanized - therapeutic use
/ Binding sites
/ Clinical trials
/ Fusion protein
/ Humanities and Social Sciences
/ Humans
/ Infant
/ Infants
/ Infections
/ Monoclonal antibodies
/ multidisciplinary
/ Proteins
/ Recombinant Proteins - therapeutic use
/ Respiratory syncytial virus
/ Respiratory Syncytial Virus Infections - drug therapy
/ Respiratory Syncytial Virus Infections - epidemiology
/ Respiratory Syncytial Virus, Human
/ Science
/ Science (multidisciplinary)
/ Susceptibility
/ Viruses
2023
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Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials
Journal Article
Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials
2023
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Overview
Nirsevimab 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.
Nirsevimab binds the respiratory syncytial virus (RSV) fusion protein and has been tested for RSV prevention in clinical trials. Here, the authors analyse RSV from infections and show that binding site substitutions are rare and that over 99% of isolates remain susceptible to nirsevimab.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/1
/ 82/1
/ 82/81
/ Antibodies, Monoclonal, Humanized - therapeutic use
/ Humanities and Social Sciences
/ Humans
/ Infant
/ Infants
/ Proteins
/ Recombinant Proteins - therapeutic use
/ Respiratory Syncytial Virus Infections - drug therapy
/ Respiratory Syncytial Virus Infections - epidemiology
/ Respiratory Syncytial Virus, Human
/ Science
/ Viruses
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