Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials
Abstract 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 analysi...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-40057-8 |
| _version_ | 1797209318036078592 |
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| author | Bahar Ahani Kevin M. Tuffy Anastasia A. Aksyuk Deidre Wilkins Michael E. Abram Ron Dagan Joseph B. Domachowske Johnathan D. Guest Hong Ji Anna Kushnir Amanda Leach Shabir A. Madhi Vaishali S. Mankad Eric A. F. Simões Benjamin Sparklin Scott D. Speer Ann Marie Stanley David E. Tabor Ulrika Wählby Hamrén Elizabeth J. Kelly Tonya Villafana |
| author_facet | Bahar Ahani Kevin M. Tuffy Anastasia A. Aksyuk Deidre Wilkins Michael E. Abram Ron Dagan Joseph B. Domachowske Johnathan D. Guest Hong Ji Anna Kushnir Amanda Leach Shabir A. Madhi Vaishali S. Mankad Eric A. F. Simões Benjamin Sparklin Scott D. Speer Ann Marie Stanley David E. Tabor Ulrika Wählby Hamrén Elizabeth J. Kelly Tonya Villafana |
| author_sort | Bahar Ahani |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-12T22:15:28Z |
| format | Article |
| id | doaj.art-fb9efa8bfa3c458ebbb25e11a772eeb6 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T09:52:47Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-fb9efa8bfa3c458ebbb25e11a772eeb62024-04-14T11:20:17ZengNature PortfolioNature Communications2041-17232023-07-0114111010.1038/s41467-023-40057-8Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trialsBahar Ahani0Kevin M. Tuffy1Anastasia A. Aksyuk2Deidre Wilkins3Michael E. Abram4Ron Dagan5Joseph B. Domachowske6Johnathan D. Guest7Hong Ji8Anna Kushnir9Amanda Leach10Shabir A. Madhi11Vaishali S. Mankad12Eric A. F. Simões13Benjamin Sparklin14Scott D. Speer15Ann Marie Stanley16David E. Tabor17Ulrika Wählby Hamrén18Elizabeth J. Kelly19Tonya Villafana20Bioinformatics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZenecaTranslational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZenecaTranslational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZenecaTranslational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZenecaTranslational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZenecaThe Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences of the Ben-Gurion University of the NegevState University of New York Upstate Medical UniversityVirology and Vaccine Discovery, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZenecaTranslational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZenecaTranslational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZenecaClinical Development, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZenecaSouth African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the WitwatersrandClinical Development, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZenecaUniversity of Colorado School of Medicine and Children’s Hospital ColoradoBioinformatics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZenecaTranslational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZenecaTranslational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZenecaTranslational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZenecaClinical Pharmacology and Quantitative Pharmacology, R&D, AstraZenecaTranslational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZenecaClinical Development, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZenecaAbstract 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.https://doi.org/10.1038/s41467-023-40057-8 |
| spellingShingle | Bahar Ahani Kevin M. Tuffy Anastasia A. Aksyuk Deidre Wilkins Michael E. Abram Ron Dagan Joseph B. Domachowske Johnathan D. Guest Hong Ji Anna Kushnir Amanda Leach Shabir A. Madhi Vaishali S. Mankad Eric A. F. Simões Benjamin Sparklin Scott D. Speer Ann Marie Stanley David E. Tabor Ulrika Wählby Hamrén Elizabeth J. Kelly Tonya Villafana Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials Nature Communications |
| title | Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials |
| title_full | Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials |
| title_fullStr | Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials |
| title_full_unstemmed | Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials |
| title_short | Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials |
| title_sort | molecular and phenotypic characteristics of rsv infections in infants during two nirsevimab randomized clinical trials |
| url | https://doi.org/10.1038/s41467-023-40057-8 |
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