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Self-assembly polymerization enhances the immunogenicity of influenza M2e peptide
Institution:1. Department of Life Sciences, Imperial College London, London, United Kingdom;2. Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA;1. Computer Science & Engineering, Indian Institute of Technology, Indore, India;2. Computer Science & Engineering, Indian Institute of Information Technology, Kota, India;3. Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia V8P 3P6, Canada;4. Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Parkallee 22, Borstel D-23845, Germany;1. Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA;2. Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA;3. Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, USA;4. Cancer Research UK Clinical Center, St. James’ University Hospital, Leeds, UK;5. University of Surrey, Guildford, UK;6. The Institute of Cancer Research, London, UK
Abstract:The extracellular domain of Influenza M2 protein (M2e) was considered as a promising target for universal influenza vaccine development. Several M2e-based influenza vaccines have been developed and many of them used a mutant M2e peptide, in which the two conserved cysteine residues were substituted by serine residues. In this paper, we compared the antigenicity and immunogenicity of wild type and cysteine-mutant M2e peptides. We found that the cysteine substitution slightly affected the antigenicity of M2e epitope, but greatly reduced the immunogenicity of M2e peptide. The cysteine substitution also disabled the M2e peptide from inducing protection against influenza virus challenge in mice. Further analysis revealed that the immunogenicity of M2e peptide was enhanced by the self-assembly of the peptide through inter-peptide disulfide bonds. These results provide new information to improve the design of M2e-based vaccines against potential influenza pandemics.
Keywords:Influenza  M2e  Vaccine
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