Immunoinformatics aided design of conserved Neuraminidase peptides containing immunodominant epitopes against Avian Influenza Virus

Abstract

Avian Influenza virus (AIV), also known as Bird Flu virus, is a type of Influenza A virus belonging to the family Orthomyxoviridae, posing a zoonotic risk. It has a broad spectrum of hosts and transmits via contact with infected animals and birds. The highly virulent AIV subtype H5N1 is currently widespread in avian populations. The virus has the potential to cross the species barrier from birds to the human population, causing fatal outcomes. There are a limited number of treatments available for bird flu, making it crucial to identify potential immunogenic peptides for diagnostics or therapeutics to combat the disease effectively. An immunoinformatics study was conducted to identify conserved immunogenic peptides consisting of multiple epitopes from the neuraminidase protein sequence of the AIV H5N1 subtype. Three conserved peptides (P1, P2, and P3) containing multiple T and B-cell epitopes were identified via various immunoinformatics tools. The peptides P1, P2, and P3 were predicted to bind with 3366 HLA class I alleles and 882 HLA class II alleles, respectively. Further, population coverage analysis using IEDB revealed more than 98% average population coverage across all six continents. These peptides were also part of previously published immunogenic peptides that have been experimentally validated. A neuraminidase immunogenic peptide construct was built by joining the three peptides with linkers, an adjuvant, and a 6x histidine tag. Followed by molecular docking with the Toll-like receptor-4 (TLR-4), which depicted stable binding affinity between the peptide constructs and TLR-4. Finally, an immune simulation study was performed which predicted the generation of peptide induced immune response. The computational analysis conducted demonstrates the immunogenic potential of specific peptides, which can be further validated via in vivo and in vitro experimental studies.