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

Nat Commun. 2022 Dec 21;13(1):7864. doi: 10.1038/s41467-022-35586-7.

Authors

Daniel Stadlbauer¹, Meagan McMahon¹, Hannah L Turner², Xueyong Zhu², Hongquan Wan³, Juan Manuel Carreño¹, George O'Dell¹, Shirin Strohmeier^{1

4}, Zain Khalil⁵, Marta Luksza^{5

6}, Harm van Bakel^{5

7}, Viviana Simon^{1

8

9

10

11}, Ali H Ellebedy¹², Ian A Wilson^{13

14}, Andrew B Ward¹⁵, Florian Krammer^{16

17

18}

Affiliations

¹ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
² Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
³ Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
⁴ Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria.
⁵ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁶ Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁷ Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁸ Global Health Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁹ Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁰ Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹¹ Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹² Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA. [email protected].
¹³ Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA. [email protected].
¹⁴ The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA. [email protected].
¹⁵ Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA. [email protected].
¹⁶ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. [email protected].
¹⁷ Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. [email protected].
¹⁸ Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai, New York, NY, USA. [email protected].

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.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Antibodies, Monoclonal* / chemistry
Antibodies, Monoclonal* / immunology
Antibodies, Viral / chemistry
Antibodies, Viral / metabolism
Catalytic Domain / immunology
Catalytic Domain / physiology
Glycosylation
Hemagglutinin Glycoproteins, Influenza Virus
Humans
Influenza A Virus, H3N2 Subtype* / immunology
Influenza A Virus, H3N2 Subtype* / metabolism
Influenza A virus
Influenza, Human / immunology
Influenza, Human / metabolism
Neuraminidase* / chemistry
Neuraminidase* / immunology

Substances

Antibodies, Monoclonal
Antibodies, Viral
Hemagglutinin Glycoproteins, Influenza Virus
Neuraminidase

Abstract

Publication types

MeSH terms

Substances

Grants and funding