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

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 () and Tonya Villafana
Additional contact information
Bahar Ahani: Bioinformatics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca
Kevin M. Tuffy: Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca
Anastasia A. Aksyuk: Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca
Deidre Wilkins: Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca
Michael E. Abram: Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca
Ron Dagan: The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences of the Ben-Gurion University of the Negev
Joseph B. Domachowske: State University of New York Upstate Medical University
Johnathan D. Guest: Virology and Vaccine Discovery, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca
Hong Ji: Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca
Anna Kushnir: Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca
Amanda Leach: Clinical Development, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca
Shabir A. Madhi: South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, Faculty of Health Sciences, University of the Witwatersrand
Vaishali S. Mankad: Clinical Development, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca
Eric A. F. Simões: University of Colorado School of Medicine and Children’s Hospital Colorado
Benjamin Sparklin: Bioinformatics, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca
Scott D. Speer: Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca
Ann Marie Stanley: Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca
David E. Tabor: Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca
Ulrika Wählby Hamrén: Clinical Pharmacology and Quantitative Pharmacology, R&D, AstraZeneca
Elizabeth J. Kelly: Translational Medicine, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca
Tonya Villafana: Clinical Development, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca

Nature Communications, 2023, vol. 14, issue 1, 1-10

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-40057-8

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