Molecular Design of Novel mRNA and Multiepitope Subunit Vaccines for H10N5 Avian Influenza A virus

Abstract

Background

Annually, influenza viruses cause a considerable number of deaths worldwide and are a primary cause of severe respiratory diseases. Finding novel immunogenic locations that might trigger a potent immune response is therefore crucial.

Methods

The present study utilized bioinformatics techniques to develop mRNA and multiepitope-based vaccines that specifically target the H10N5 Avian Influenza A virus. The epitopes of the hemagglutinin (HA) and neuraminidase (NA) proteins on T and B cells of this specific strain were identified using a variety of immunoinformatic techniques. The chosen HTL epitopes and their corresponding major histocompatibility complex (MHC) alleles were docked by using a molecular docking technique.

Results

A total of 6 linear B cell epitopes, 6 HTL epitopes, and 6 CTL epitopes were chosen for the structural design of preventive vaccines based on mRNA and multiepitope subunit. At physiological pH the developed vaccines demonstrated strong antigenicity, little toxicity, and non-allergenic qualities. The generated multiepitope subunit vaccine for Flu GC content and CAI value, which were determined to be 49.41% and 0.975%, respectively, were assessed using the codon optimization tool. The stable expression of the vaccine in the pET28aþ vector is confirmed by the GC content and CAI value. A significant degree of immune responses was found by in silico immunological simulation. The top ranked docking pose (HDOCK model 3) from ten models was subjected to 100 ns all-atom MD simulation in AMBER22 with the ff19SB force field in explicit OPC water. An average of 6.8 inter-chain hydrogen bonds, in addition to favourable short-range Coulomb (− 1,032 kJ/mol) and Lennard-Jones (− 436 kJ/mol) interaction energies, continued to maintain contact between the interfaces. Using molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) and molecular mechanics/generalized Born surface area (MM/GBSA) methods, the calculated free energies are ΔGbind of − 83.30 ± 29.20 and − 94.72 ± 29.41 kcal/mol, respectively, and the residues Lys381, Arg569, Lys396, Glu237, and Glu527 are identified as the leading contributors to the binding free energy. Thus, the constructed vaccine against avian influenza H10N5 A viral strain showed high potential.

Conclusion

The vaccine candidate demonstrated promising computational characteristics and requires experimental validation.