Human anti-N1 monoclonal antibodies elicited by pandemic H1N1 virus infection broadly inhibit HxN1 viruses in vitro and in vivo

Lena Hansen; Meagan McMahon; Hannah L. Turner; Xueyong Zhu; Jackson S. Turner; Gabriel Ozorowski; Daniel Stadlbauer; Juha Vahokoski; Aaron J. Schmitz; Amena A. Rizk; Wafaa B. Alsoussi; Shirin Strohmeier; Wenli Yu; José Alberto Choreño-Parra; Luis Jiménez-Alvarez; Alfredo Cruz-Lagunas; Joaquín Zúñiga; Philip A. Mudd; Rebecca J. Cox; Ian A. Wilson; Andrew B. Ward; Ali H. Ellebedy; Florian Krammer

doi:10.1016/j.immuni.2023.07.004

Human anti-N1 monoclonal antibodies elicited by pandemic H1N1 virus infection broadly inhibit HxN1 viruses in vitro and in vivo

Lena Hansen, Meagan McMahon, Hannah L. Turner, Xueyong Zhu, Jackson S. Turner, Gabriel Ozorowski, Daniel Stadlbauer, Juha Vahokoski, Aaron J. Schmitz, Amena A. Rizk, Wafaa B. Alsoussi, Shirin Strohmeier, Wenli Yu, José Alberto Choreño-Parra, Luis Jiménez-Alvarez, Alfredo Cruz-Lagunas, Joaquín Zúñiga, Philip A. Mudd, Rebecca J. Cox, Ian A. WilsonAndrew B. Ward, Ali H. Ellebedy, Florian Krammer

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

9 Scopus citations

Abstract

Neuraminidase (NA) is one of the two influenza virus surface glycoproteins, and antibodies that target it are an independent correlate of protection. However, our current understanding of NA antigenicity is incomplete. Here, we describe human monoclonal antibodies (mAbs) from a patient with a pandemic H1N1 virus infection in 2009. Two mAbs exhibited broad reactivity and inhibited NA enzyme activity of seasonal H1N1 viruses circulating before and after 2009, as well as viruses with avian or swine N1s. The mAbs provided robust protection from lethal challenge with human H1N1 and avian H5N1 viruses in mice, and both target an epitope on the lateral face of NA. In summary, we identified two broadly protective NA antibodies that share a novel epitope, inhibited NA activity, and provide protection against virus challenge in mice. Our work reaffirms that NA should be included as a target in future broadly protective or universal influenza virus vaccines.

Original language	English
Pages (from-to)	1927-1938.e8
Journal	Immunity
Volume	56
Issue number	8
DOIs	https://doi.org/10.1016/j.immuni.2023.07.004
State	Published - 8 Aug 2023

Keywords

antibody
influenza virus
neuraminidase

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10.1016/j.immuni.2023.07.004

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Hansen, L., McMahon, M., Turner, H. L., Zhu, X., Turner, J. S., Ozorowski, G., Stadlbauer, D., Vahokoski, J., Schmitz, A. J., Rizk, A. A., Alsoussi, W. B., Strohmeier, S., Yu, W., Choreño-Parra, J. A., Jiménez-Alvarez, L., Cruz-Lagunas, A., Zúñiga, J., Mudd, P. A., Cox, R. J., ... Krammer, F. (2023). Human anti-N1 monoclonal antibodies elicited by pandemic H1N1 virus infection broadly inhibit HxN1 viruses in vitro and in vivo. Immunity, 56(8), 1927-1938.e8. https://doi.org/10.1016/j.immuni.2023.07.004

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title = "Human anti-N1 monoclonal antibodies elicited by pandemic H1N1 virus infection broadly inhibit HxN1 viruses in vitro and in vivo",

abstract = "Neuraminidase (NA) is one of the two influenza virus surface glycoproteins, and antibodies that target it are an independent correlate of protection. However, our current understanding of NA antigenicity is incomplete. Here, we describe human monoclonal antibodies (mAbs) from a patient with a pandemic H1N1 virus infection in 2009. Two mAbs exhibited broad reactivity and inhibited NA enzyme activity of seasonal H1N1 viruses circulating before and after 2009, as well as viruses with avian or swine N1s. The mAbs provided robust protection from lethal challenge with human H1N1 and avian H5N1 viruses in mice, and both target an epitope on the lateral face of NA. In summary, we identified two broadly protective NA antibodies that share a novel epitope, inhibited NA activity, and provide protection against virus challenge in mice. Our work reaffirms that NA should be included as a target in future broadly protective or universal influenza virus vaccines.",

keywords = "antibody, influenza virus, neuraminidase",

author = "Lena Hansen and Meagan McMahon and Turner, {Hannah L.} and Xueyong Zhu and Turner, {Jackson S.} and Gabriel Ozorowski and Daniel Stadlbauer and Juha Vahokoski and Schmitz, {Aaron J.} and Rizk, {Amena A.} and Alsoussi, {Wafaa B.} and Shirin Strohmeier and Wenli Yu and Chore{\~n}o-Parra, {Jos{\'e} Alberto} and Luis Jim{\'e}nez-Alvarez and Alfredo Cruz-Lagunas and Joaqu{\'i}n Z{\'u}{\~n}iga and Mudd, {Philip A.} and Cox, {Rebecca J.} and Wilson, {Ian A.} and Ward, {Andrew B.} and Ellebedy, {Ali H.} and Florian Krammer",

note = "Publisher Copyright: {\textcopyright} 2023 Elsevier Inc.",

year = "2023",

month = aug,

day = "8",

doi = "10.1016/j.immuni.2023.07.004",

language = "English",

volume = "56",

pages = "1927--1938.e8",

journal = "Immunity",

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Hansen, L, McMahon, M, Turner, HL, Zhu, X, Turner, JS, Ozorowski, G, Stadlbauer, D, Vahokoski, J, Schmitz, AJ, Rizk, AA, Alsoussi, WB, Strohmeier, S, Yu, W, Choreño-Parra, JA, Jiménez-Alvarez, L, Cruz-Lagunas, A, Zúñiga, J, Mudd, PA, Cox, RJ, Wilson, IA, Ward, AB, Ellebedy, AH & Krammer, F 2023, 'Human anti-N1 monoclonal antibodies elicited by pandemic H1N1 virus infection broadly inhibit HxN1 viruses in vitro and in vivo', Immunity, vol. 56, no. 8, pp. 1927-1938.e8. https://doi.org/10.1016/j.immuni.2023.07.004

TY - JOUR

T1 - Human anti-N1 monoclonal antibodies elicited by pandemic H1N1 virus infection broadly inhibit HxN1 viruses in vitro and in vivo

AU - Hansen, Lena

AU - McMahon, Meagan

AU - Turner, Hannah L.

AU - Zhu, Xueyong

AU - Turner, Jackson S.

AU - Ozorowski, Gabriel

AU - Stadlbauer, Daniel

AU - Vahokoski, Juha

AU - Schmitz, Aaron J.

AU - Rizk, Amena A.

AU - Alsoussi, Wafaa B.

AU - Strohmeier, Shirin

AU - Yu, Wenli

AU - Choreño-Parra, José Alberto

AU - Jiménez-Alvarez, Luis

AU - Cruz-Lagunas, Alfredo

AU - Zúñiga, Joaquín

AU - Mudd, Philip A.

AU - Cox, Rebecca J.

AU - Wilson, Ian A.

AU - Ward, Andrew B.

AU - Ellebedy, Ali H.

AU - Krammer, Florian

PY - 2023/8/8

Y1 - 2023/8/8

N2 - Neuraminidase (NA) is one of the two influenza virus surface glycoproteins, and antibodies that target it are an independent correlate of protection. However, our current understanding of NA antigenicity is incomplete. Here, we describe human monoclonal antibodies (mAbs) from a patient with a pandemic H1N1 virus infection in 2009. Two mAbs exhibited broad reactivity and inhibited NA enzyme activity of seasonal H1N1 viruses circulating before and after 2009, as well as viruses with avian or swine N1s. The mAbs provided robust protection from lethal challenge with human H1N1 and avian H5N1 viruses in mice, and both target an epitope on the lateral face of NA. In summary, we identified two broadly protective NA antibodies that share a novel epitope, inhibited NA activity, and provide protection against virus challenge in mice. Our work reaffirms that NA should be included as a target in future broadly protective or universal influenza virus vaccines.

AB - Neuraminidase (NA) is one of the two influenza virus surface glycoproteins, and antibodies that target it are an independent correlate of protection. However, our current understanding of NA antigenicity is incomplete. Here, we describe human monoclonal antibodies (mAbs) from a patient with a pandemic H1N1 virus infection in 2009. Two mAbs exhibited broad reactivity and inhibited NA enzyme activity of seasonal H1N1 viruses circulating before and after 2009, as well as viruses with avian or swine N1s. The mAbs provided robust protection from lethal challenge with human H1N1 and avian H5N1 viruses in mice, and both target an epitope on the lateral face of NA. In summary, we identified two broadly protective NA antibodies that share a novel epitope, inhibited NA activity, and provide protection against virus challenge in mice. Our work reaffirms that NA should be included as a target in future broadly protective or universal influenza virus vaccines.

KW - antibody

KW - influenza virus

KW - neuraminidase

UR - http://www.scopus.com/inward/record.url?scp=85166927830&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2023.07.004

DO - 10.1016/j.immuni.2023.07.004

M3 - Article

C2 - 37506693

AN - SCOPUS:85166927830

SN - 1074-7613

VL - 56

SP - 1927-1938.e8

JO - Immunity

JF - Immunity

IS - 8

ER -

Human anti-N1 monoclonal antibodies elicited by pandemic H1N1 virus infection broadly inhibit HxN1 viruses in vitro and in vivo

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Keywords

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