Characterizing evolutionarily conserved influenza A virus sequences as vaccine targets

Abstract

Influenza A viruses generate an extreme genetic diversity through point mutation and gene segment exchange, resulting in many new strains that emerge from the animal reservoirs, among which was the emergence of highly pathogenic H5N1 virus. With the possibility of an influenza pandemic, a vaccine that will protect against any influenza A subtype/strain is a critical need. One feasible approach is a vaccine containing conserved immunogenic protein sequences that represent the genotypic diversity of the currently known and newly emerged avian and human influenza viruses as an alternative to current vaccines that address only the known circulating virus strains. In this thesis, tools and methodologies for automated aggregation and annotation of influenza A virus sequences from public databases and identification of highly conserved sequences based on user-defined parameters were developed. The identified highly conserved and immune-relevant sequences are suitable candidates for a T-cell epitope-based vaccine designed to provide a continuum of immune responses to influenza A infection.