Protection against Influenza A Virus Challenge with M2e-Displaying Filamentous Escherichia coli Phages

PLoS One. 2015 May 14;10(5):e0126650. doi: 10.1371/journal.pone.0126650. eCollection 2015.

Abstract

Human influenza viruses are responsible for annual epidemics and occasional pandemics that cause severe illness and mortality in all age groups worldwide. Matrix protein 2 (M2) of influenza A virus is a tetrameric type III membrane protein that functions as a proton-selective channel. The extracellular domain of M2 (M2e) is conserved in human and avian influenza A viruses and is being pursued as a component for a universal influenza A vaccine. To develop a M2e vaccine that is economical and easy to purify, we genetically fused M2e amino acids 2-16 to the N-terminus of pVIII, the major coat protein of filamentous bacteriophage f88. We show that the resulting recombinant f88-M2e2-16 phages are replication competent and display the introduced part of M2e on the phage surface. Immunization of mice with purified f88-M2e2-16 phages in the presence of incomplete Freund's adjuvant, induced robust M2e-specific serum IgG and protected BALB/c mice against challenge with human and avian influenza A viruses. Thus, replication competent filamentous bacteriophages can be used as efficient and economical carriers to display conserved B cell epitopes of influenza A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Antigens, Viral / biosynthesis
  • Antigens, Viral / immunology
  • Capsid Proteins / chemistry
  • Capsid Proteins / genetics*
  • Coliphages / immunology*
  • Coliphages / isolation & purification
  • Coliphages / physiology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza A Virus, H1N1 Subtype / metabolism
  • Influenza Vaccines / immunology
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Orthomyxoviridae Infections / prevention & control
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / genetics
  • Viral Matrix Proteins / chemistry
  • Viral Matrix Proteins / genetics*
  • Virus Replication

Substances

  • Antibodies, Viral
  • Antigens, Viral
  • Capsid Proteins
  • Immunoglobulin G
  • Influenza Vaccines
  • M2 protein, Influenza A virus
  • Recombinant Fusion Proteins
  • Viral Matrix Proteins

Grants and funding

L.D. was supported by State Scholarship Fund (File No. 2011674067) from the China Scholarship Council (http://www.csc.edu.cn/) and by Belgian Federal Sciences Administration Project BELVIR p7/45 (http://www.dmipfmv.ulg.ac.be/vetimmuno/indexPAI.html). K.R. is supported by FP7 project FLUNIVAC (http://flunivac.eu/). This research was also supported by Fonds voor Wetenschappelijk Onderzoek Research Project G052412N (http://www.fwo.be/) and Ghent University Special Research Grant BOF12/GOA/014 (http://www.ugent.be/nl/onderzoek/financiering/bof). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.