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Excavating chikungunya genome to design B and T cell multi-epitope subunit vaccine using comprehensive immunoinformatics approach to control chikungunya infection

Author:
Narula, Aruna, Pandey, Rajan Kumar, Khatoon, Nazia, Mishra, Amit, Prajapati, Vijay Kumar
Source:
Infection, genetics, and evolution 2018 v.61 pp. 4-15
ISSN:
1567-1348
Subject:
B-lymphocytes, Chikungunya virus, adjuvants, cytotoxic T-lymphocytes, epitopes, evolution, genetic vectors, genome, immunoinformatics, immunologic receptors, innate immunity, interferon-gamma, molecular dynamics, molecular models, mortality, prediction, subunit vaccines, viral nonstructural proteins
Abstract:
Chikungunya infection has been a cause of countless deaths worldwide. Due to lack of permanent treatment and prevention of this disease, the mortality rate remains very high. Therefore, we followed an immunoinformatics approach for the development of multi-epitope subunit vaccine which is able to elucidate humoral, cell-mediated and innate immune responses inside the host body. Both structural and non-structural proteins of chikungunya virus were utilized for prediction of B-cell and T-cell binding epitopes along with interferon-γ (IFN-γ) inducing epitopes. The vaccine construct is composed of β-defensin as an adjuvant at the N-terminal followed by Cytotoxic T-Lymphocytes (CTL) and Helper T-Lymphocyte (HTL) epitopes. The same vaccine construct was also utilized for the prediction of B-cell binding epitopes and IFN-γ inducing epitopes. This was followed by the 3D model generation, refinement and validation of the vaccine construct. Later on, the interaction of modeled vaccine with the innate immune receptor (TLR-3) was explored by performing molecular docking and molecular dynamics simulation studies. Also to check the efficiency of expression of this vaccine construct in an expression vector, in silico cloning was performed at the final stage of vaccine development. Further, designed multi-epitope subunit vaccine necessitates experimental and clinical investigation to develop as an immunogenic vaccine candidate.
Agid:
5919911