Antibodies targeting the neuraminidase active site inhibit influenza H3N2 viruses with an S245N glycosylation site

Daniel Stadlbauer; Meagan McMahon; Hannah L. Turner; Xueyong Zhu; Hongquan Wan; Juan Manuel Carreño; George O’Dell; Shirin Strohmeier; Zain Khalil; Marta Luksza; Harm van Bakel; Viviana Simon; Ali H. Ellebedy; Ian A. Wilson; Andrew B. Ward; Florian Krammer

doi:10.1038/s41467-022-35586-7

Antibodies targeting the neuraminidase active site inhibit influenza H3N2 viruses with an S245N glycosylation site

Daniel Stadlbauer, Meagan McMahon, Hannah L. Turner, Xueyong Zhu, Hongquan Wan, Juan Manuel Carreño, George O’Dell, Shirin Strohmeier, Zain Khalil, Marta Luksza, Harm van Bakel, Viviana Simon, Ali H. Ellebedy, Ian A. Wilson, Andrew B. Ward, Florian Krammer

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6 Scopus citations

Abstract

Contemporary influenza A H3N2 viruses circulating since 2016 have acquired a glycosylation site in the neuraminidase in close proximity to the enzymatic active site. Here, we investigate if this S245N glycosylation site, as a result of antigenic evolution, can impact binding and function of human monoclonal antibodies that target the conserved active site. While we find that a reduction in the inhibitory ability of neuraminidase active site binders is measurable, this class of broadly reactive monoclonal antibodies maintains protective efficacy in vivo.

Original language	English
Article number	7864
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-35586-7
State	Published - Dec 2022

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Stadlbauer, D., McMahon, M., Turner, H. L., Zhu, X., Wan, H., Carreño, J. M., O’Dell, G., Strohmeier, S., Khalil, Z., Luksza, M., van Bakel, H., Simon, V., Ellebedy, A. H., Wilson, I. A., Ward, A. B., & Krammer, F. (2022). Antibodies targeting the neuraminidase active site inhibit influenza H3N2 viruses with an S245N glycosylation site. Nature Communications, 13(1), Article 7864. https://doi.org/10.1038/s41467-022-35586-7

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title = "Antibodies targeting the neuraminidase active site inhibit influenza H3N2 viruses with an S245N glycosylation site",

abstract = "Contemporary influenza A H3N2 viruses circulating since 2016 have acquired a glycosylation site in the neuraminidase in close proximity to the enzymatic active site. Here, we investigate if this S245N glycosylation site, as a result of antigenic evolution, can impact binding and function of human monoclonal antibodies that target the conserved active site. While we find that a reduction in the inhibitory ability of neuraminidase active site binders is measurable, this class of broadly reactive monoclonal antibodies maintains protective efficacy in vivo.",

author = "Daniel Stadlbauer and Meagan McMahon and Turner, {Hannah L.} and Xueyong Zhu and Hongquan Wan and Carre{\~n}o, {Juan Manuel} and George O{\textquoteright}Dell and Shirin Strohmeier and Zain Khalil and Marta Luksza and {van Bakel}, Harm and Viviana Simon and Ellebedy, {Ali H.} and Wilson, {Ian A.} and Ward, {Andrew B.} and Florian Krammer",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41467-022-35586-7",

language = "English",

volume = "13",

journal = "Nature Communications",

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Stadlbauer, D, McMahon, M, Turner, HL, Zhu, X, Wan, H, Carreño, JM, O’Dell, G, Strohmeier, S, Khalil, Z, Luksza, M , van Bakel, H , Simon, V, Ellebedy, AH, Wilson, IA, Ward, AB & Krammer, F 2022, 'Antibodies targeting the neuraminidase active site inhibit influenza H3N2 viruses with an S245N glycosylation site', Nature Communications, vol. 13, no. 1, 7864. https://doi.org/10.1038/s41467-022-35586-7

TY - JOUR

T1 - Antibodies targeting the neuraminidase active site inhibit influenza H3N2 viruses with an S245N glycosylation site

AU - Stadlbauer, Daniel

AU - McMahon, Meagan

AU - Turner, Hannah L.

AU - Zhu, Xueyong

AU - Wan, Hongquan

AU - Carreño, Juan Manuel

AU - O’Dell, George

AU - Strohmeier, Shirin

AU - Khalil, Zain

AU - Luksza, Marta

AU - van Bakel, Harm

AU - Simon, Viviana

AU - Ellebedy, Ali H.

AU - Wilson, Ian A.

AU - Ward, Andrew B.

AU - Krammer, Florian

PY - 2022/12

Y1 - 2022/12

N2 - Contemporary influenza A H3N2 viruses circulating since 2016 have acquired a glycosylation site in the neuraminidase in close proximity to the enzymatic active site. Here, we investigate if this S245N glycosylation site, as a result of antigenic evolution, can impact binding and function of human monoclonal antibodies that target the conserved active site. While we find that a reduction in the inhibitory ability of neuraminidase active site binders is measurable, this class of broadly reactive monoclonal antibodies maintains protective efficacy in vivo.

AB - Contemporary influenza A H3N2 viruses circulating since 2016 have acquired a glycosylation site in the neuraminidase in close proximity to the enzymatic active site. Here, we investigate if this S245N glycosylation site, as a result of antigenic evolution, can impact binding and function of human monoclonal antibodies that target the conserved active site. While we find that a reduction in the inhibitory ability of neuraminidase active site binders is measurable, this class of broadly reactive monoclonal antibodies maintains protective efficacy in vivo.

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U2 - 10.1038/s41467-022-35586-7

DO - 10.1038/s41467-022-35586-7

M3 - Article

C2 - 36543789

AN - SCOPUS:85144593437

SN - 2041-1723

VL - 13

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 7864

ER -

Antibodies targeting the neuraminidase active site inhibit influenza H3N2 viruses with an S245N glycosylation site

Abstract

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