In-depth phylodynamics, evolutionary analysis and in silico predictions of universal epitopes of Influenza A subtypes and Influenza B viruses

Abstract

This study applied High-Performance Computing to explore the high-resolution phylodynamics and the evolutionary dynamics of Influenza viruses (IVs) A and B and their subtypes in-depth to identify peptide-based candidates for broad-spectrum vaccine targets. For this purpose, we collected all the available Hemagglutinin (HA) and Neuraminidase (NA) nucleotide and amino acid sequences (more than 100,000) of IVs isolated from all the reservoirs and intermediate hosts species, from all geographic ranges and from different isolation sources, covering a period of almost one century of sampling years. We highlight that despite the constant changes in Influenza evolutionary dynamics over time, which are responsible for the generation of novel strains, our study identified the presence of highly conserved peptides distributed in all the HA and NA found in H1-H18 and N1-N11 IAV subtypes and IBVs. Additionally, predictions through computational methods showed that these peptides could have a strong affinity to bind to HLA-A∗02:01/HLA-DRB1∗01:01 major histocompatibility complex (MHC) class I and II molecules, therefore acting as a double ligand. Moreover, epitope prediction in antigens from pathogens responsible for secondary bacterial infection was also studied. These findings show that the regions mapped here may potentially be explored as universal epitope-based candidates to develop therapies leading to a broader response against the infection induced by all circulating IAVs, IBVs and Influenza-associated bacterial infections.

Keywords: Epitope mapping; Evolutionary analyses; Influenza viruses; Phylodynamics; Viral molecular evolution.