Protection against the mouse-adapted A/FM/1/47 strain of influenza A virus in mice by a monoclonal antibody with cross-neutralizing activity among H1 and H2 strains.

Abstract The non-structural protein 1 (NS1) of influenza A virus (IAV) is a multifunctional protein that antagonizes host antiviral responses, modulating virus pathogenesis. As such, it serves as a good target for research and diagnostic assay development. In this study, we have generated a novel monoclonal antibody (mAb) 19H9 and epitope mapping revealed that two residues, P85 and Y89, of NS1 are essential for interacting with this mAb. Furthermore, residues P85 and Y89 are found to be highly conserved across different IAV subtypes, namely seasonal H1N1 and H3N2, as well as the highly pathogenic H5N1 and H5N6 avian strains. Indeed, mAb 19H9 exhibits broad cross-reactivity with IAV strains of different subtypes. The binding of mAb 19H9 to residue Y89 was further confirmed by the abrogation of interaction between NS1 and p85β. Additionally, mAb 19H9 also detected NS1 proteins expressed in IAV-infected cells, showing NS1 intracellular localization in the cytoplasm and nucleolus. To our knowledge, mAb 19H9 is the first murine mAb to bind at the juxtaposition between the N-terminal RNA-binding domain and C-terminal effector domain of NS1. It could serve as a useful research tool for studying the conformational plasticity and dynamic changes in NS1.

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In VitroAssessment of the Immunological Significance of a Human Monoclonal Antibody Directed to the Influenza A Virus Nucleoprotein

Clinical and Vaccine Immunology ◽

10.1128/cvi.00339-13 ◽

2013 ◽

Vol 20 (8) ◽

pp. 1333-1337 ◽

Cited By ~ 24

Author(s):

Rogier Bodewes ◽

Martina M. Geelhoed-Mieras ◽

Jens Wrammert ◽

Rafi Ahmed ◽

Patrick C. Wilson ◽

...

Keyword(s):

Monoclonal Antibody ◽

Influenza A Virus ◽

Influenza A ◽

Viral Antigen ◽

Human Monoclonal Antibody ◽

Cell Cytotoxicity ◽

Influenza A Viruses ◽

Dependent Cell ◽

Infected Cells

ABSTRACTInfluenza A viruses cause annual epidemics and occasionally pandemics. Antibodies directed to the conserved viral nucleoprotein (NP) may play a role in immunity against various influenza A virus subtypes. Here, we assessed the immunological significance of a human monoclonal antibody directed to NPin vitro. This antibody bound to virus-infected cells but did not display virus-neutralizing activity, complement-dependent cell cytotoxicity, or opsonization of viral antigen for improved antigen presentation to CD8+T cells by dendritic cells.

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Crystal Structure of the Conserved Amino Terminus of the Extracellular Domain of Matrix Protein 2 of Influenza A Virus Gripped by an Antibody

Journal of Virology ◽

10.1128/jvi.02105-15 ◽

2015 ◽

Vol 90 (1) ◽

pp. 611-615 ◽

Cited By ~ 18

Author(s):

Ki Joon Cho ◽

Bert Schepens ◽

Kristof Moonens ◽

Lei Deng ◽

Walter Fiers ◽

...

Keyword(s):

Crystal Structure ◽

Monoclonal Antibody ◽

Binding Site ◽

Influenza A Virus ◽

Influenza A ◽

Matrix Protein ◽

Antibody Binding ◽

Amino Terminus ◽

Antibody Binding Site ◽

Protective Antibodies

We report the crystal structure of the M2 ectodomain (M2e) in complex with a monoclonal antibody that binds the amino terminus of M2. M2e extends into the antibody binding site to form an N-terminal β-turn near the bottom of the paratope. This M2e folding differs significantly from that of M2e in complex with an antibody that binds another part of M2e. This suggests that M2e can adopt at least two conformations that can elicit protective antibodies.

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