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

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.

• Authors: Lei Deng, Lorena Itatí Ibañez, Veronique Van den Bossche, Kenny Roose, Sameh A Youssef, Alain de Bruin, Walter Fiers, Xavier Saelens
• Journal: PloS one (PLoS One) Vol. 10 Issue 5 Pg. e0126650 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 25973787 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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