Immunoinformatics-Driven Design of a Self-Amplifying mRNA Vaccine Against Human Herpesvirus 6 Advancing Viral Immunoprophylaxis
DOI:
https://doi.org/10.64229/rmv1k712Keywords:
Human herpesvirus 6, Self-amplifying mRNA vaccine, Multi epitope vaccine, Immunoinformatics, Reverse vaccinologyAbstract
Human Herpesvirus 6 (HHV-6) is a common virus characterized by its double-stranded DNA structure that infects almost everyone by early childhood. While usually mild, HHV-6 poses serious health threats to people with weakened immune systems, contributing to neurological issues like encephalitis and adding complications in organ transplant cases. Despite its ubiquity and potential risks, there is currently no licensed vaccine to prevent either HHV-6 infection or reactivation. In this study, an immunoinformatics and reverse vaccinology approach was employed to design a self-amplifying mRNA (saRNA) multi-epitope vaccine targeting HHV-6. Four immunogenic viral proteins were screened, leading to the identification of 8 B-cell epitopes, 8 cytotoxic T lymphocyte (CTL) epitopes, and 8 helper T lymphocyte (HTL) epitopes, all exhibiting strong antigenicity and non-allergenic, non-toxic profiles. These epitopes were assembled into four vaccine constructs using optimized linkers and adjuvanted with the 50S ribosomal L7/L12 protein to enhance immunogenicity. Among the constructs, V3 demonstrated the most favorable physicochemical properties and structural stability. Molecular docking analyses revealed strong binding of V3 with Toll-like receptor 4 (TLR4), achieving a ClusPro docking score of -361.46 and a HADDOCK score of -5.3 ± 4.1, supported by stable electrostatic and van der Waals interactions. Normal mode analysis (NMA) confirmed the structural stability of the V3-TLR4 complex, with a low eigenvalue indicative of favorable conformational dynamics. Immune simulations using C-ImmSim predicted robust primary, secondary, and tertiary immune responses, characterized by immunoglobulin class switching, memory B- and T-cell generation, and a Th1-biased cytokine profile. Codon optimization and in silico cloning further validated the feasibility of vaccine expression and downstream experimental testing. Collectively, these findings highlight the potential of the proposed HHV-6 saRNA multi-epitope vaccine as a promising prophylactic candidate, warranting further in vitro and in vivo validation.
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