Kinetic MUNANA assay reveals functionally relevant antibody epitopes on Influenza A virus neuraminidase

Abstract Influenza A virus neuraminidase (NA) is drawing attention as a target for vaccine development. In this study, we propose kinetic MUNANA assay as a tool to identify monoclonal antibodies (mAbs) that specifically target functional epitopes on NA. By analyzing changes in the parameters of the...

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Main Authors: Ilya V. Smirnov, Danica F. Besavilla, Karin Schön, Hannes Axelsson, Davide Angeletti
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:npj Viruses
Online Access:https://doi.org/10.1038/s44298-025-00123-y
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author Ilya V. Smirnov
Danica F. Besavilla
Karin Schön
Hannes Axelsson
Davide Angeletti
author_facet Ilya V. Smirnov
Danica F. Besavilla
Karin Schön
Hannes Axelsson
Davide Angeletti
author_sort Ilya V. Smirnov
collection DOAJ
description Abstract Influenza A virus neuraminidase (NA) is drawing attention as a target for vaccine development. In this study, we propose kinetic MUNANA assay as a tool to identify monoclonal antibodies (mAbs) that specifically target functional epitopes on NA. By analyzing changes in the parameters of the Michaelis-Menten curve (Km and Vmax), we revealed distinct mechanisms of Ab-mediated inhibition. Additionally, we developed a web-based application facilitating efficient processing of the assay results and enabling statistical inference. We employed the kinetic MUNANA assay to test newly developed mAbs targeting NA of the widely used PR8 H1N1 strain. Among these, mAbs with strong effect on NA enzymatic parameters were more likely to select for escape mutants that had a substantial impact on the overall enzymatic activity of the virus. In summary, when combined with ELLA, kinetic MUNANA is a rapid method to profile the putative binding site and the effect of NA-specific mAbs.
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spelling doaj-art-9ad91d936111477683edce6535ae641a2025-08-20T02:15:25ZengNature Portfolionpj Viruses2948-17672025-05-013111110.1038/s44298-025-00123-yKinetic MUNANA assay reveals functionally relevant antibody epitopes on Influenza A virus neuraminidaseIlya V. Smirnov0Danica F. Besavilla1Karin Schön2Hannes Axelsson3Davide Angeletti4Department of Microbiology and Immunology, Institute of Biomedicine, University of GothenburgDepartment of Microbiology and Immunology, Institute of Biomedicine, University of GothenburgDepartment of Microbiology and Immunology, Institute of Biomedicine, University of GothenburgDepartment of Microbiology and Immunology, Institute of Biomedicine, University of GothenburgDepartment of Microbiology and Immunology, Institute of Biomedicine, University of GothenburgAbstract Influenza A virus neuraminidase (NA) is drawing attention as a target for vaccine development. In this study, we propose kinetic MUNANA assay as a tool to identify monoclonal antibodies (mAbs) that specifically target functional epitopes on NA. By analyzing changes in the parameters of the Michaelis-Menten curve (Km and Vmax), we revealed distinct mechanisms of Ab-mediated inhibition. Additionally, we developed a web-based application facilitating efficient processing of the assay results and enabling statistical inference. We employed the kinetic MUNANA assay to test newly developed mAbs targeting NA of the widely used PR8 H1N1 strain. Among these, mAbs with strong effect on NA enzymatic parameters were more likely to select for escape mutants that had a substantial impact on the overall enzymatic activity of the virus. In summary, when combined with ELLA, kinetic MUNANA is a rapid method to profile the putative binding site and the effect of NA-specific mAbs.https://doi.org/10.1038/s44298-025-00123-y
spellingShingle Ilya V. Smirnov
Danica F. Besavilla
Karin Schön
Hannes Axelsson
Davide Angeletti
Kinetic MUNANA assay reveals functionally relevant antibody epitopes on Influenza A virus neuraminidase
npj Viruses
title Kinetic MUNANA assay reveals functionally relevant antibody epitopes on Influenza A virus neuraminidase
title_full Kinetic MUNANA assay reveals functionally relevant antibody epitopes on Influenza A virus neuraminidase
title_fullStr Kinetic MUNANA assay reveals functionally relevant antibody epitopes on Influenza A virus neuraminidase
title_full_unstemmed Kinetic MUNANA assay reveals functionally relevant antibody epitopes on Influenza A virus neuraminidase
title_short Kinetic MUNANA assay reveals functionally relevant antibody epitopes on Influenza A virus neuraminidase
title_sort kinetic munana assay reveals functionally relevant antibody epitopes on influenza a virus neuraminidase
url https://doi.org/10.1038/s44298-025-00123-y
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