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

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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. Madh, 2023. "Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40057-8
    DOI: 10.1038/s41467-023-40057-8
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    Cited by:

    1. Estefany Rios-Guzman & Lacy M. Simons & Taylor J. Dean & Francesca Agnes & Anna Pawlowski & Arghavan Alisoltanidehkordi & Hannah H. Nam & Michael G. Ison & Egon A. Ozer & Ramon Lorenzo-Redondo & Judd , 2024. "Deviations in RSV epidemiological patterns and population structures in the United States following the COVID-19 pandemic," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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