In-silico Design of Multi-epitope Vaccine against Nipah Virus using Immunoinformatics Approach

Nipah virus is a pleomorphic virus that causes high mortality with unpredictable outbreaks. The virus also shows high zoonotic potential with long term neurological damage after recovery further adding to the disease burden. An in-silico epitope-based vaccine offers a promising solution to supplement wider efforts to control the viral spread. This is achieved through immunoinformatics approach using a plethora of servers available. We derived cytotoxic T-cell, T-Helper, B-cell and IFN-γ targeting epitopes from surface glycoprotein G. Cytotoxic T-cell specific epitopes, HLA-B*4402, chimeric multiepitope vaccine structures were prepared using homology modelling method. The structures were validated using various methods and docking simulation was performed between epitopes and HLA-B*4402. Similarly, the vaccine construct was docked to Toll like receptor-4 and a molecular dynamics simulation was performed to assess stability of interaction. Both the docking simulations showed stable interactions with their respective receptors. Immune-simulation was carried out to validate the efficacy of vaccine candidate which showed elevated levels of antibodies such as IgM and IgG due to increase in active B cell population. Both in-vitro and in-vivo serological analysis is required for confirmation of vaccine potency. To facilitate this effort, codon optimization was undertaken to remove existing codon bias. The optimized gene sequence was cloned into the PUC19 vector to express in Escherichia coli K12 strain. Additionally, a poly histidine (6xHis) tag was added at the C-terminal end to ease the purification step. The immune-informatics approach hopes to accelerate vaccine development process to reduce the risk of attenuation while increasing the success rates of pre-clinical trials.