Designing a multi-epitope vaccine against chickenpox virus using in silico approach

Abstract

Abstract Human Herpesvirus 3 (HHV3), commonly known as the Varicella zoster virus (VZV), is a highly infectious α-herpesvirus that causes Varicella (chicken pox) on primary infection, as well as Herpes zoster (shingles) on latent reactivation. Life-threatening sequelae and complications such as post-herpetic neuralgia (PHN), meningoencephalitis, myelopathy, skin necrosis, etc. have also been observed in some immunocompromised individuals. Although effective vaccines have been developed against VZV, they are limited by the scope of vaccination and in some cases by the vaccine efficacy. Addressing the need for a much safer and more efficient vaccine, an in-silico approach-based study was carried out to design a multi-epitope vaccine against VZV. Accounting for their crucial role in the viral entry mechanism, the envelope glycoproteins were analyzed for potent epitopes that can induce cytotoxic T cells, Helper T cells, and B cells. These epitopes were further screened using various computational tools, for constructing a multi-epitope vaccine, via the addition of suitable linkers and an adjuvant. Antigenicity, allergenicity, conservancy, population coverage, and other physiochemical properties of the final vaccine construct were evaluated, post which their structural properties and the interaction patterns with TLR1 and TLR4 were analyzed. Further, the vaccine construct was subjected to molecular dynamics simulation studies, in order to assess its structural stability. Finally, the multi-epitope vaccine was codon optimized and cloned into the expression vector pET-28a+, to have it expressed efficiently in the K12 strain of E.Coli bacteria. The immune reactions triggered by the vaccine candidate were validated using immune simulation studies. Laboratory validation of the findings for its immunogenicity and safety can help in assessing the in vivo efficiency of the vaccine to prevent VZV infection.