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Monoclonal antibodies targeting the influenza virus N6 neuraminidase

Shirin Strohmeier, Fatima Amanat, Juan Manuel Carreño, View ORCID ProfileFlorian Krammer
doi: https://doi.org/10.1101/2021.02.15.431355
Shirin Strohmeier
aDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
bDepartment of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria
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Fatima Amanat
aDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
cGraduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA
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Juan Manuel Carreño
aDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Florian Krammer
aDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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  • ORCID record for Florian Krammer
  • For correspondence: florian.krammer@mssm.edu
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Abstract

Influenza A viruses are a diverse species that include 16 hemagglutinin (HA) subtypes and 9 neuraminidase (NA) subtypes. While the antigenicity of many HA subtypes is reasonably well studied, less is known about NA antigenicity, especially when it comes to non-human subtypes that only circulate in animal reservoirs. The N6 NA subtypes are mostly found in viruses infecting birds. However, they have also been identified in viruses that infect mammals, such as swine and seals. More recently, highly pathogenic H5N6 subtype viruses have caused rare infections and mortality in humans. Here, we generated murine mAbs to the N6 NA, characterized their breadth and antiviral properties in vitro and in vivo and mapped their epitopes by generating escape mutant viruses. We found that the antibodies had broad reactivity across the American and Eurasian N6 lineages, but relatively little binding and inhibition of the H5N6 NA. Several of the antibodies exhibited strong NA inhibition activity and some also showed activity in the antibody dependent cellular cytotoxicity reporter assay and neutralization assay. In addition, we generated escape mutant viruses for six monoclonal antibodies and found mutations on the lateral ridge of the NA. Lastly, we observed variable protection in H4N6 and H5N6 mouse challenge models when the antibodies were given prophylactically.

Importance The N6 NA has recently gained prominence due to the emergence of highly pathogenic H5N6 viruses. Currently, there is limited characterization of the antigenicity of avian N6 neuraminidase. Our data is an important first step towards a better understanding of the N6 NA antigenicity.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted February 16, 2021.
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Monoclonal antibodies targeting the influenza virus N6 neuraminidase
Shirin Strohmeier, Fatima Amanat, Juan Manuel Carreño, Florian Krammer
bioRxiv 2021.02.15.431355; doi: https://doi.org/10.1101/2021.02.15.431355
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Monoclonal antibodies targeting the influenza virus N6 neuraminidase
Shirin Strohmeier, Fatima Amanat, Juan Manuel Carreño, Florian Krammer
bioRxiv 2021.02.15.431355; doi: https://doi.org/10.1101/2021.02.15.431355

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