Immunoinformatics approach for a novel multi-epitope subunit vaccine design against various subtypes of Influenza A virus

Abstract

Vaccination is the best strategy for the control and prevention of contagious diseases caused by Influenza A viruses. Extraordinary genetic variability and continual evolvability are responsible for the virus having survival and adaptation to host cell immune response, thus rendering the current influenza vaccines with suboptimal effectiveness.Therefore, in the present study, using a novel immunoinformatics approach, we have designed a universal influenza subunit vaccine based on the highly conserved epitopic sequences of rapidly evolving (HA), a moderately evolving (NP) and slow evolving (M1) proteins of the virus. The vaccine design includes 2 peptide adjuvants, 26 CTL epitopes, 9 HTL epitopes, and 7 linear BCL epitopes to induce innate, cellular, and humoral immune responses against Influenza A viruses. We also analyzed the physicochemical properties of the designed construct to validate its thermodynamic stability, hydrophilicity, PI, antigenicity, and allergenicity. Furthermore, we predicted a highly stable tertiary model of the designed subunit vaccine, wherein additional disulfide bonds were incorporated to enhance its stability. The molecular docking and molecular dynamics simulations of the refined vaccine model with TLR3, TLR7, TLR8, MHC-I and MHC-II showed stable vaccine and receptors complexes, thus confirming the immunogenicity of the designed vaccine. Collectively, these findings suggest that our multi-epitope vaccine construct may confer protection against various strains of influenza A virus subtypes, which could prevent the need for annual reformulation of vaccine and alleviate disease burden.

Keywords: Cytotoxic T cell epitopes; Helper T cell epitopes; Immunoinformatics; Influenza A virus; Innate immunity; Vaccine.