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.

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