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

Immunity. 2023 Aug 8;56(8):1927-1938.e8. doi: 10.1016/j.immuni.2023.07.004. Epub 2023 Jul 27.

Authors

Lena Hansen¹, Meagan McMahon², Hannah L Turner³, Xueyong Zhu³, Jackson S Turner⁴, Gabriel Ozorowski³, Daniel Stadlbauer², Juha Vahokoski⁵, Aaron J Schmitz⁴, Amena A Rizk⁴, Wafaa B Alsoussi⁴, Shirin Strohmeier², Wenli Yu³, José Alberto Choreño-Parra⁶, Luis Jiménez-Alvarez⁷, Alfredo Cruz-Lagunas⁷, Joaquín Zúñiga⁶, Philip A Mudd⁸, Rebecca J Cox¹, Ian A Wilson⁹, Andrew B Ward¹⁰, Ali H Ellebedy¹¹, Florian Krammer¹²

Affiliations

¹ Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Microbiology, Haukeland University Hospital, Bergen, Norway.
² Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
³ Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
⁴ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
⁵ Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway; National Advisory Unit for Tropical Infectious Diseases, Haukeland University Hospital, Bergen, Norway.
⁶ Laboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico; Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico.
⁷ Laboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico.
⁸ Department of Emergency Medicine, Washington University School of Medicine, St. Louis, MO, USA.
⁹ Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: [email protected].
¹⁰ Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: [email protected].
¹¹ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA; Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, St. Louis, MO, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: [email protected].
¹² Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Pathology, Molecular and Cell-based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: [email protected].

PMID: 37506693
PMCID: PMC10529248 (available on 2024-08-08)
DOI: 10.1016/j.immuni.2023.07.004

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Monoclonal* / isolation & purification
Antibodies, Monoclonal* / metabolism
Antibodies, Viral* / isolation & purification
Antibodies, Viral* / metabolism
Cryoelectron Microscopy
Disease Models, Animal
Epitopes
Humans
Immunoglobulin Fab Fragments / chemistry
Influenza A Virus, H1N1 Subtype*
Influenza, Human* / drug therapy
Mice
Mice, Inbred BALB C
Neuraminidase* / chemistry
Neuraminidase* / metabolism

Substances

Antibodies, Monoclonal
Antibodies, Viral
Neuraminidase
NA protein, influenza A virus
Immunoglobulin Fab Fragments
Epitopes

Abstract

Publication types

MeSH terms

Substances

Grants and funding