Abstract

Kaposi’s sarcoma-associated herpesvirus (KSHV) responsible for causing Kaposi sarcoma (KS), an opportunistic angioproliferative neoplasm is emerging rapidly. Despite this there is no permanent cure for this disease. The present study was aimed to design a multi-epitope based vaccine targeting the major glycoproteins of KSHV which plays an important role in the virus entry. After the application of rigorous immunoinformatics analysis and several immune filters, the multi-epitope vaccine was constructed, consisting of CD4, CD8 and IFN-γ inducing epitopes. Several physiochemical characteristics, allergenicity and antigenicity of the multi-epitope vaccine were analyzed in order to ensure its safety and immunogenicity. Further, the binding affinity and stability of the vaccine with Toll like receptor -9 (TLR-9) was analyzed by molecular docking and dynamics simulation studies. In addition, an in silico cloning was performed to ensure the expression and translation efficiency of the vaccine, utilizing pET-28a (+) vector. Such T-cell-based immunotherapies which leverage this mechanism could prove their potential against cancer. Further, the authors propose to test the present findings in the lab settings to ensure the safety, immunogenicity and efficacy of the presented vaccine which may help in controlling KSHV infection.

Highlights

  • Kaposi’s sarcoma-associated herpesvirus (KSHV), formally named as Human Herpes Virus-8 (HHV-8), is responsible for causing cancer - Kaposi’s sarcoma, commonly occurring in Acquired Immune Deficiency Syndrome (AIDS) patients, multicentric Castleman’s disease, primary effusion lymphoma and KSHV inflammatory cytokine syndrome1

  • The statistical analysis indicates that the KHSV has grown rapidly among HIV infected patients

  • Many antivirals have been tested so far against KHSV, none proved to be completely effective against the disease

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Summary

Introduction

KSHV, formally named as Human Herpes Virus-8 (HHV-8), is responsible for causing cancer - Kaposi’s sarcoma, commonly occurring in Acquired Immune Deficiency Syndrome (AIDS) patients, multicentric Castleman’s disease, primary effusion lymphoma and KSHV inflammatory cytokine syndrome. The vaccines designed by conventional methods comprise of large proteins or whole organism incorporating unnecessary antigenic load and the chances of inducing allergenic response is increased. These limitations can be overcome by using peptide based vaccines which are composed of short immunogenic peptide fragments that could elicit the highly targeted immune responses, thereby avoiding the chances of allergenic response. A multi-epitope vaccine comprising a series of peptides that could induce the activation of both humoral and adaptive immune response is an ideal strategy for prevention and treatment of viral or tumor infections. The present study was aimed to design a multi-epitope vaccine against HHV-8 comprising of Cytotoxic T cell lymphocytes (CTL), Helper T cell lymphocytes (HTL), Interferon-gamma (IFN-γ) inducing and B epitopes

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