scholarly journals In-Silico Design of Envelope based Multi-epitope Vaccine Candidate Against Kyasanur Forest Disease Virus

Author(s):  
Sathishkumar Arumugam

Abstract Kyasanur Forest Disease Virus (KFDV) causing common tick-borne hemorrhagic fever in south India, there is no approved anti-viral or efficacious vaccine against this disease. Recent KFDV spread into new geographic locations gives urgent call for development of new vaccine and drugs. In this study, we adapted in-silico approach to design multi-epitope subunit vaccine for KFDV. Conserved regions of KFDV envelope protein sequences reported during 1962 to 2016 were identified. Eight different immuno-informatics tools were employed to predict the linear B-cell and T-cell epitopes, high scored and/or multi-immunogenic epitopes were linked together and obtained two vaccine candidates (VC1 and VC2). Obtained vaccine candidates were found to be non-allergic and had good antigenic properties, also gives the cross-protection against to Alkhurma Hemorrhagic Fever virus (AHFV). The 3D structures of vaccine candidates were built and validated. Docking of vaccine candidates with toll-like receptor-8 (TLR-8) was performed by Hex 8.0 and Cluspro, highest binding energy observed between VC2 and TLR8. JCAT sever confirmed cloning efficiency of both vaccine constructs and in-silico cloning into pET30a (+) vector by SnapGene suggests successful translation of vaccine constructs. In this study, multi-epitope vaccine candidates were designed and validated, it paves the way for up-coming vaccine and diagnostic kit development.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sathishkumar Arumugam ◽  
Prasad Varamballi

AbstractKyasanur forest disease virus (KFDV) causing tick-borne hemorrhagic fever which was earlier endemic to western Ghats, southern India, it is now encroaching into new geographic regions, but there is no approved medicine or effective vaccine against this deadly disease. In this study, we did in-silico design of multi-epitope subunit vaccine for KFDV. B-cell and T-cell epitopes were predicted from conserved regions of KFDV envelope protein and two vaccine candidates (VC1 and VC2) were constructed, those were found to be non-allergic and possess good antigenic properties, also gives cross-protection against Alkhurma hemorrhagic fever virus. The 3D structures of vaccine candidates were built and validated. Docking analysis of vaccine candidates with toll-like receptor-2 (TLR-2) by Cluspro and PatchDock revealed strong affinity between VC1 and TLR2. Ligplot tool was identified the intermolecular hydrogen bonds between vaccine candidates and TLR-2, iMOD server confirmed the stability of the docking complexes. JCAT sever ensured cloning efficiency of both vaccine constructs and in-silico cloning into pET30a (+) vector by SnapGene showed successful translation of epitope region. IMMSIM server was identified increased immunological responses. Finally, multi-epitope vaccine candidates were designed and validated their efficiency, it may pave the way for up-coming vaccine and diagnostic kit development.


2016 ◽  
Author(s):  
Sandeep Saini ◽  
Chander Jyoti ◽  
Varinder Kumar

RNAs are versatile biomolecules and can be coding or non-coding. Among the non-coding RNAs, miRNAs are small endogenous molecules that play important role in posttranscriptional gene regulation. miRNAs are identified in viruses too and involved in down regulation of host genes. Flavivirus family members are classified in to two groups: mosquito-borne flaviviruses (MBFV) and tick-borne flaviviruses (TBFV). Kyasanur forest disease virus (KFDV) found in India in 1957 (Karnataka) relates to TBFV. Virus has been diffuse to new areas in India and needs attention as it can cause severe hemorrhagic fever. Here in this study, we scanned the virus genome for prediction of miRNAs that can inhibit host target genes. VMir, tool was used for extraction of pre-miRNAs. A total of four miRNAs were found and submitted to ViralMir for classification in to real or pseudo. Interestingly, all four pre-miRNAs were classified as real. Eight mature miRNAs were located in pre-miRNAs by Mature Bayes. A total of 539 human target genes has been identified by using miRDB but ANGPT1 (angiopoietin 1) and TFRC (transferrin receptor) genes were screened to play role in hemorrhagic fever and neurological problems. GO analysis of target genes also supported the evidences.


npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Bharti Bhatia ◽  
Kimberly Meade-White ◽  
Elaine Haddock ◽  
Friederike Feldmann ◽  
Andrea Marzi ◽  
...  

AbstractKyasanur Forest disease virus (KFDV) is a tick-borne flavivirus endemic in India known to cause severe hemorrhagic and encephalitic disease in humans. In recent years, KFDV has spread beyond its original endemic zone raising public health concerns. Currently, there is no treatment available for KFDV but a vaccine with limited efficacy is used in India. Here, we generated two new KFDV vaccine candidates based on the vesicular stomatitis virus (VSV) platform. We chose the VSV-Ebola virus (VSV-EBOV) vector either with the full-length or a truncated EBOV glycoprotein as the vehicle to express the precursor membrane (prM) and envelope (E) proteins of KFDV (VSV-KFDV). For efficacy testing, we established a mouse disease model by comparing KFDV infections in three immunocompetent mouse strains (BALB/c, C57Bl/6, and CD1). Both vaccine vectors provided promising protection against lethal KFDV challenge in the BALB/c model following prime-only prime-boost and immunizations. Only prime-boost immunization with VSV-KFDV expressing full-length EBOV GP resulted in uniform protection. Hyperimmune serum derived from prime-boost immunized mice protected naïve BALB/c mice from lethal KFDV challenge indicating the importance of antibodies for protection. The new VSV-KFDV vectors are promising vaccine candidates to combat an emerging, neglected public health problem in a densely populated part of the world.


2020 ◽  
Vol 8 (9) ◽  
pp. 1406
Author(s):  
Bharti Bhatia ◽  
Heinz Feldmann ◽  
Andrea Marzi

Kyasanur Forest disease virus (KFDV) and Alkhurma hemorrhagic fever virus (AHFV) are tick-borne flaviviruses that cause life-threatening hemorrhagic fever in humans with case fatality rates of 3–5% for KFDV and 1–20% for AHFV, respectively. Both viruses are biosafety level 4 pathogens due to the severity of disease they cause and the lack of effective countermeasures. KFDV was discovered in India and is restricted to parts of the Indian subcontinent, whereas AHFV has been found in Saudi Arabia and Egypt. In recent years, both viruses have spread beyond their original endemic zones and the potential of AHFV to spread through ticks on migratory birds is a public health concern. While there is a vaccine with limited efficacy for KFDV used in India, there is no vaccine for AHFV nor are there any therapeutic concepts to combat infections with these viruses. In this review, we summarize the current knowledge about pathogenesis, vector distribution, virus spread, and infection control. We aim to bring attention to the potential public health threats posed by KFDV and AHFV and highlight the urgent need for the development of effective countermeasures.


2009 ◽  
Vol 15 (2) ◽  
pp. 326-328 ◽  
Author(s):  
Jinglin Wang ◽  
Hailin Zhang ◽  
Shihong Fu ◽  
Huanyu Wang ◽  
Daxin Ni ◽  
...  

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