Immunoinformatic based multi-epitope vaccine design and validation against Kyasanur forest disease: A tick borne viral infection.

Abstract

Background objectives: Kyasanur Forest Disease (KFD) is a tick-borne viral illness prevalent in the Western Ghats region of India, posing a significant public health concern. The current formalin-inactivated KFDV vaccine exhibits modest efficacy, necessitating the development of more potent preventive measures.

Methods: This study employed immunoinformatic modelling techniques to design a multiepitope-based vaccine subunit targeting humoral and cell-mediated immune responses against KFDV. The vaccine was constructed using helper T cell (CD4+), cytotoxic T cell (CD8+), and B cell epitopes, linked together with appropriate linkers and an adjuvant β-defensin at the N-terminus, resulting in a 704 amino acid long vaccine subunit. Evaluation parameters included immunogenic potency, allergenicity, solubility, toxicity, and population coverage. Predictions of secondary and three-dimensional (3D) structure were made, followed by docking studies with Toll-like receptor-3 (TLR3) and major histocompatibility complex (MHC-I and II) to assess binding affinity. Additionally, simulation of the vaccine and TLR3 construct was performed using the iMod server to further analyze their interaction dynamics.

Results: The developed vaccine subunit exhibited favorable structural and dynamic stability, with strong binding affinity to target receptors. Codon optimization and in silico cloning analysis indicated high vaccine expression and potency. Immune stimulation studies revealed enhanced production of IgG, IgM, helper T cells, cytotoxic T cells, INF-gamma, and IL-2, indicative of robust immune response against KFDV.

Interpretation conclusion: The developed vaccine construct was structurally and dynamically stable and produced a strong immune response against KFDV. However, further animal model studies are needed to assess the efficacy and safety of these vaccines for the prevention of KFDV. The vaccine subunit structure was submitted to the ModelArchive database (https://www.modelarchive.org/doi/10.5452/ma-ij19q).