Selective Engagement of FcγRIV by a M2e-Specific Single Domain Antibody Construct Protects Against Influenza A Virus Infection.

Amino Acid Sequence Animals Antibodies, Bispecific / chemistry Antibodies, Viral / chemistry Cell Line Humans Influenza A virus / immunology Influenza, Human / immunology Mice Models, Molecular Peptides / chemistry Protein Conformation Receptors, IgG / chemistry Single-Domain Antibodies / chemistry Structure-Activity Relationship Viral Matrix Proteins / chemistry
Fcγ receptor effector functions influenza matrix protein 2 ectodomain single domain antibody

Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2019
Historique:
received: 16 09 2019
accepted: 27 11 2019
entrez: 11 1 2020
pubmed: 11 1 2020
medline: 11 11 2020
Statut: epublish

Résumé

Lower respiratory tract infections, such as infections caused by influenza A viruses, are a constant threat for public health. Antivirals are indispensable to control disease caused by epidemic as well as pandemic influenza A. We developed a novel anti-influenza A virus approach based on an engineered single-domain antibody (VHH) construct that can selectively recruit innate immune cells to the sites of virus replication. This protective construct comprises two VHHs. One VHH binds with nanomolar affinity to the conserved influenza A matrix protein 2 (M2) ectodomain (M2e). Co-crystal structure analysis revealed that the complementarity determining regions 2 and 3 of this VHH embrace M2e. The second selected VHH specifically binds to the mouse Fcγ Receptor IV (FcγRIV) and was genetically fused to the M2e-specific VHH, which resulted in a bi-specific VHH-based construct that could be efficiently expressed in

Identifiants

DOI: 10.3389/fimmu.2019.02920 PMID: 31921179 PMC: PMC6921966
pubmed: 31921179
doi: 10.3389/fimmu.2019.02920
pmc: PMC6921966
doi:

Substances chimiques

Antibodies, Bispecific 0
Antibodies, Viral 0
FCGR3A protein, human 0
M2 protein, Influenza A virus 0
Peptides 0
Receptors, IgG 0
Single-Domain Antibodies 0
Viral Matrix Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2920

Informations de copyright

Copyright © 2019 De Vlieger, Hoffmann, Van Molle, Nerinckx, Van Hoecke, Ballegeer, Creytens, Remaut, Hengel, Schepens and Saelens.

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Auteurs

Dorien De Vlieger (D)

VIB-UGent Center for Medical Biotechnology, VIB, Ghent, Belgium.
Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium.

Katja Hoffmann (K)

Institute of Virology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Inge Van Molle (I)

Structural Biology Brussels, Vrije Universiteit Brussel, Brussels, Belgium.
VIB-VUB Center for Structural Biology, Brussels, Belgium.

Wim Nerinckx (W)

VIB-UGent Center for Medical Biotechnology, VIB, Ghent, Belgium.
Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium.

Lien Van Hoecke (L)

VIB-UGent Center for Medical Biotechnology, VIB, Ghent, Belgium.
Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.

Marlies Ballegeer (M)

VIB-UGent Center for Medical Biotechnology, VIB, Ghent, Belgium.
Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium.

Sarah Creytens (S)

VIB-UGent Center for Medical Biotechnology, VIB, Ghent, Belgium.
Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium.

Han Remaut (H)

Structural Biology Brussels, Vrije Universiteit Brussel, Brussels, Belgium.
VIB-VUB Center for Structural Biology, Brussels, Belgium.

Hartmut Hengel (H)

Institute of Virology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Bert Schepens (B)

VIB-UGent Center for Medical Biotechnology, VIB, Ghent, Belgium.
Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.

Xavier Saelens (X)

VIB-UGent Center for Medical Biotechnology, VIB, Ghent, Belgium.
Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium.

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Classifications MeSH

questionsmedicales.fr › Sciences de l'information › Sources d'information › Services d'information › Documentation › Données de séquences moléculaires › Séquence d'acides aminés › Selective Engagement of FcγRIV by a...
questionsmedicales.fr › Eucaryotes › Animaux › Selective Engagement of FcγRIV by a...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps bispécifiques › Selective Engagement of FcγRIV by a...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps antiviraux › Selective Engagement of FcγRIV by a...
questionsmedicales.fr › Cellules › Cellules cultivées › Lignée cellulaire › Selective Engagement of FcγRIV by a...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Selective Engagement of FcγRIV by a...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN de polarité négative › Orthomyxoviridae › Influenzavirus A › Virus de la grippe A › Selective Engagement of FcγRIV by a...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Grippe humaine › Selective Engagement of FcγRIV by a...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Selective Engagement of FcγRIV by a...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles moléculaires › Selective Engagement of FcγRIV by a...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Selective Engagement of FcγRIV by a...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Selective Engagement of FcγRIV by a...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteur Fc › Récepteurs du fragment Fc des IgG › Selective Engagement of FcγRIV by a...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Fragments d'immunoglobuline › Fragments Fab d'immunoglobuline › Anticorps à domaine unique › Selective Engagement of FcγRIV by a...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Relation structure-activité › Selective Engagement of FcγRIV by a...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines virales › Protéines virales structurales › Protéines de l'enveloppe virale › Protéines de la matrice virale › Selective Engagement of FcγRIV by a...