Hierarchical and redundant roles of activating FcγRs in protection against influenza disease by M2e-specific IgG1 and IgG2a antibodies

Silvie Van den Hoecke, Katrin Ehrhardt, Annasaheb Kolpe, Karim El Bakkouri, Lei Deng, Hendrik Grootaert, Steve Schoonooghe, Anouk Smet, Mostafa Bentahir, Kenny Roose, Michael Schotsaert, Bert Schepens, Nico Callewaert, Falk Nimmerjahn, Peter Staeheli, Hartmut Hengel, Xavier Saelens

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

The ectodomain of matrix protein 2 is a universal influenza A virus vaccine candidate that provides protection through antibody-dependent effector mechanisms. Here we compared the functional engagement of Fcγ receptor (FcγR) family members by two M2e-specific monoclonal antibodies (MAbs), MAb 37 (IgG1) and MAb 65 (IgG2a), which recognize a similar epitope in M2e with similar affinities. The binding of MAb 65 to influenza A virus-infected cells triggered all three activating mouse Fcγ receptors in vitro, whereas MAb 37 activated only FcγRIII. The passive transfer of MAb 37 or MAb 65 in wild-type, Fcer1g-/-, Fcgr3-/-, and Fcgr1-/- Fcgr3-/- BALB/c mice revealed the importance of these receptors for protection against influenza A virus challenge, with a clear requirement of FcγRIII for IgG1 MAb 37 being found. We also report that FcγRIV contributes to protection by M2especific IgG2a antibodies.

Original languageEnglish
Article numbere02500-16
JournalJournal of Virology
Volume91
Issue number7
DOIs
StatePublished - 2017

Keywords

  • Fcγ receptors
  • IgG antibody isotype
  • Influenza A virus
  • M2e
  • Mechanism of protection
  • Viral infection

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