THE ANTIGENIC DIVERSITY ANALYSIS OF COMPLETE VIRAL GENOME OF INFLUENZA A VIRUS

Abstract

Antigenic drift and shift of influenza A virus result in change of antigenic composition that require annual redesign of influenza vaccine. Variation of responses to vaccines has been observed in populations – due to diversity of viral antigens and of the human immune system. Some 10,000 influenza A protein sequences of human and animal origins have been published in public databases. Therefore a combined approach, using bioinformatics and experimental validation, is required for systematic analysis of viral diversity. We applied a novel computational method for the analysis of antigenic diversity of ten influenza A antigens from human isolates. From 3821 initial sequences, we derived 1352 sequences that encode the complete antigenic diversity of human influenza A virus proteins. Using computational system MULTIPRED, we identified Tcell epitope hot spots for three common human leukocyte antigen (HLA) supertypes (A2, A3, and DR). On average there are five hot spots, comprising 18% of full sequence length, in influenza A virus hemagglutinin (HA) and neuraminidase (NA) for each of the three studied HLA supertypes. Peptides from these predicted hot spot regions were further analysed to identify minimal set of peptides that represent the antigenic diversity of these hot spots. Approximately 100 peptides in total were identified for HA and NA subtypes from the hot spots of each HLA supertype – these represent potential targets for wet lab experimental validation for vaccine design.