Bispecific T cell engaging antibody constructs targeting a universally conserved part of the viral M2 ectodomain cure and prevent influenza A virus infection

Jochen Pendzialek; Kenny Roose; Anouk Smet; Bert Schepens; Peter Kufer; Tobias Raum; Patrick A Baeuerle; Markus Muenz; Xavier Saelens; Walter Fiers

doi:10.1016/j.antiviral.2017.02.016

Bispecific T cell engaging antibody constructs targeting a universally conserved part of the viral M2 ectodomain cure and prevent influenza A virus infection

Antiviral Res. 2017 May:141:155-164. doi: 10.1016/j.antiviral.2017.02.016. Epub 2017 Mar 1.

Authors

Affiliations

¹ ARM, Amgen Research (Munich) GmbH, Munich, Germany.
² Medical Biotechnology Center, VIB, Technologiepark 927, 9052, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, 9052, Ghent, Belgium.
³ Medical Biotechnology Center, VIB, Technologiepark 927, 9052, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, 9052, Ghent, Belgium. Electronic address: [email protected].

PMID: 28257797
DOI: 10.1016/j.antiviral.2017.02.016

Abstract

The ectodomain of the influenza A matrix protein 2 (M2e) is highly conserved amongst all influenza virus A subtypes. M2e is present on the surface of influenza A virus-infected cells, and therefore a suitable target for broadly protective therapies. We designed bispecific T cell engaging (BiTE^®) antibody constructs specific for M2e by genetically fusing a single chain variable fragment (scFv) derived from an M2e-specific murine monoclonal antibody with a CD3ɛ-specific scFv. These so-called FLU BiTE^® antibody constructs selectively mediate T cell dependent lysis of M2-expressing and influenza A virus infected cells and protect BALB/c mice against challenge with different influenza A virus subtypes. By humanizing the M2e-binding scFv, we generated human-like FLU BiTE^® antibody constructs, with increased in vitro cytotoxic activity and in vivo protective capacity against influenza A virus infection. FLU BiTE^® antibody constructs represent a promising new curative and prophylactic treatment option for influenza disease.

Keywords: Antiviral; Bispecific T cell engaging antibody constructs; Influenza virus; M2 ectodomain.

Publication types

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

MeSH terms

Animals
Antibodies, Bispecific / administration & dosage
Antibodies, Bispecific / immunology*
Antibodies, Monoclonal / administration & dosage
Antibodies, Monoclonal, Humanized / administration & dosage
Antibodies, Monoclonal, Humanized / immunology
Antibodies, Viral / blood
Cytotoxicity Tests, Immunologic
Immunologic Memory
Influenza A virus / chemistry*
Influenza A virus / immunology*
Influenza Vaccines / administration & dosage
Mice
Orthomyxoviridae Infections / prevention & control*
T-Lymphocytes / immunology*
Viral Matrix Proteins / immunology*

Substances

Antibodies, Bispecific
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Antibodies, Viral
Influenza Vaccines
M2 protein, Influenza A virus
Viral Matrix Proteins