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; Tonya Villafana

doi:10.1038/s41467-023-40057-8

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. KellyTonya Villafana

Faculty of Health Sciences

Research output: Contribution to journal › Article › peer-review

34 Scopus citations

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.

Original language	English
Article number	4347
Journal	Nature Communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-40057-8
State	Published - 1 Dec 2023

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-023-40057-8

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Ahani, B., Tuffy, K. M., Aksyuk, A. A., Wilkins, D., Abram, M. E., Dagan, R., Domachowske, J. B., Guest, J. D., Ji, H., Kushnir, A., Leach, A., Madhi, S. A., Mankad, V. S., Simões, E. A. F., Sparklin, B., Speer, S. D., Stanley, A. M., Tabor, D. E., Hamrén, U. W., ... Villafana, T. (2023). Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials. Nature Communications, 14(1), Article 4347. https://doi.org/10.1038/s41467-023-40057-8

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title = "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 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.",

author = "Bahar Ahani and Tuffy, {Kevin M.} and Aksyuk, {Anastasia A.} and Deidre Wilkins and Abram, {Michael E.} and Ron Dagan and Domachowske, {Joseph B.} and Guest, {Johnathan D.} and Hong Ji and Anna Kushnir and Amanda Leach and Madhi, {Shabir A.} and Mankad, {Vaishali S.} and Sim{\~o}es, {Eric A.F.} and Benjamin Sparklin and Speer, {Scott D.} and Stanley, {Ann Marie} and Tabor, {David E.} and Hamr{\'e}n, {Ulrika W{\"a}hlby} and Kelly, {Elizabeth J.} and Tonya Villafana",

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year = "2023",

month = dec,

day = "1",

doi = "10.1038/s41467-023-40057-8",

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Ahani, B, Tuffy, KM, Aksyuk, AA, Wilkins, D, Abram, ME, Dagan, R, Domachowske, JB, Guest, JD, Ji, H, Kushnir, A, Leach, A, Madhi, SA, Mankad, VS, Simões, EAF, Sparklin, B, Speer, SD, Stanley, AM, Tabor, DE, Hamrén, UW, Kelly, EJ & Villafana, T 2023, 'Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials', Nature Communications, vol. 14, no. 1, 4347. https://doi.org/10.1038/s41467-023-40057-8

TY - JOUR

T1 - Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials

AU - Ahani, Bahar

AU - Tuffy, Kevin M.

AU - Aksyuk, Anastasia A.

AU - Wilkins, Deidre

AU - Abram, Michael E.

AU - Dagan, Ron

AU - Domachowske, Joseph B.

AU - Guest, Johnathan D.

AU - Ji, Hong

AU - Kushnir, Anna

AU - Leach, Amanda

AU - Madhi, Shabir A.

AU - Mankad, Vaishali S.

AU - Simões, Eric A.F.

AU - Sparklin, Benjamin

AU - Speer, Scott D.

AU - Stanley, Ann Marie

AU - Tabor, David E.

AU - Hamrén, Ulrika Wählby

AU - Kelly, Elizabeth J.

AU - Villafana, Tonya

PY - 2023/12/1

Y1 - 2023/12/1

N2 - 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.

AB - 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.

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U2 - 10.1038/s41467-023-40057-8

DO - 10.1038/s41467-023-40057-8

M3 - Article

C2 - 37468530

AN - SCOPUS:85165382159

SN - 2041-1723

VL - 14

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 4347

ER -

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

Abstract

ASJC Scopus subject areas

UN SDGs

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