Computational vaccinology guided design of multi-epitopes subunit vaccine designing against Hantaan virus and its validation through immune simulations.

The Hantaan virus belongs to Bunyaviridae family, an emerging virus that is responsible for hemorrhagic fevers. The virus is distributed worldwide and as of now there is no successful antiviral drug or vaccine developed to protect against the viral infections. Immunization or vaccination is an alternative approach for the protection against viral infections. A cost effective and thermodynamically stable vaccine should be developed to prevent a future possible pandemic. In this study a vaccine candidate was designed against the Hantaan virus, multiple immunoinformatics and reverse vaccinology tools were utilized for the prediction of both B and T cell epitopes for Nuceloprotein, RNA dependent RNA polymerase L and Envelope protein of the Hantaan virus. The individual epitopes were modeled for docking with respective HLAs and a multi-epitopes subunit vaccine candidate was constructued by joining together carefully evaluated B and T cell epitopes with suitable linkers. The vaccine model was evaluated for several physiochameical parameters i.e. Molecular weight, instability index and aliphatic index among the others, followed by 3D modeling of the vaccine for docking with TLR-4. Based on previous studies, Human beta-defensin was liked at the N-terminus of the vaccine sequence as an adjuvant to enhance immunogenicity. The docked complexes of vaccine-TLR-4 were then evaluated for residual interactions. Moreover, to validate final vaccine construct, immune simulations was carried out by C-IMMSIM server. A natural immune reponse was predicted by the immune simulation analysis. In-silico cloning was carried out using E. coli as host resulting in 0.93 CAI value, which suggests that the vaccine construct will attain maximal expression in E. coli host. The vaccine designed in this study needs experimental verification to confirm the immunogenicity and efficacy of the vaccine and ultimately used against Hantaan virus associated infections.