Designing a multi-epitopes subunit vaccine against human herpes virus 6A based on molecular dynamics and immune stimulation

Abstract

Human Herpesvirus 6A (HHV-6A) is a prevalent virus associated with various clinical manifestations, including neurological disorders, autoimmune diseases, and promotes tumor cell growth. HHV-6A is an enveloped, double-stranded DNA virus with a genome of approximately 160–170 kb containing a hundred open-reading frames. An immunoinformatics approach was applied to predict high immunogenic and non-allergenic CTL, HTL, and B cell epitopes and design a multi-epitope subunit vaccine based on HHV-6A glycoprotein B (gB), glycoprotein H (gH), and glycoprotein Q (gQ). The stability and correct folding of the modeled vaccines were confirmed through molecular dynamics simulation. Molecular docking found that the designed vaccines have a strong binding network with human TLR3, with Kd values of 1.5E-11 mol/L, 2.6E-12 mol/L, 6.5E-13 mol/L, and 7.1E-11 mol/L for gB-TLR3, gH-TLR3, gQ-TLR3, and the combined vaccine-TLR3, respectively. The codon adaptation index values of the vaccines were above 0.8, and their GC content was around 67 % (normal range 30–70 %), indicating their potential for high expression. Immune simulation analysis demonstrated robust immune responses against the vaccine, with approximately 650,000/ml combined IgG and IgM antibody titer. This study lays a strong foundation for developing a safe and effective vaccine against HHV-6A, with significant implications for treating associated conditions.