scholarly journals A live-attenuated viral vector vaccine protects mice against lethal challenge with Kyasanur Forest disease virus

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Bharti Bhatia ◽  
Kimberly Meade-White ◽  
Elaine Haddock ◽  
Friederike Feldmann ◽  
Andrea Marzi ◽  
...  
Keyword(s):  
Public Health ◽  
Disease Virus ◽  
Viral Vector ◽  
Public Health Problem ◽  
Full Length ◽  
Mouse Strains ◽  
Hyperimmune Serum ◽  
Vaccine Candidates ◽  
Forest Disease ◽  
Kyasanur Forest Disease

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.

scholarly journals In-silico design of envelope based multi-epitope vaccine candidate against Kyasanur forest disease virus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sathishkumar Arumugam ◽  
Prasad Varamballi
Keyword(s):  
Disease Virus ◽  
In Silico ◽  
Hemorrhagic Fever ◽  
Epitope Vaccine ◽  
Epitope Region ◽  
Vaccine Candidates ◽  
Forest Disease ◽  
In Silico Design ◽  
Antigenic Properties ◽  
Kyasanur Forest Disease

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.

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

2021 ◽  
Author(s):  
Sathishkumar Arumugam
Keyword(s):  
Disease Virus ◽  
In Silico ◽  
Hemorrhagic Fever ◽  
T Cell Epitopes ◽  
Epitope Vaccine ◽  
Vaccine Candidates ◽  
Forest Disease ◽  
Hemorrhagic Fever Virus ◽  
Antigenic Properties ◽  
Kyasanur Forest Disease

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.

scholarly journals Isolation of Kyasanur Forest Disease Virus from Febrile Patient, Yunnan, China

2009 ◽  
Vol 15 (2) ◽  
pp. 326-328 ◽  
Author(s):  
Jinglin Wang ◽  
Hailin Zhang ◽  
Shihong Fu ◽  
Huanyu Wang ◽  
Daxin Ni ◽  
...  
Keyword(s):  
Disease Virus ◽  
Febrile Patient ◽  
Forest Disease ◽  
Kyasanur Forest Disease

scholarly journals 20Forest loss shapes the landscape suitability of Kyasanur Forest disease in the Western Ghats, India

2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Michael Walsh ◽  
Siobhan Mor ◽  
Hindol Maity ◽  
Shah Hossain
Keyword(s):  
Public Health ◽  
Species Richness ◽  
Western Ghats ◽  
Mammalian Species ◽  
Forest Loss ◽  
Anthropogenic Pressure ◽  
Forest Disease ◽  
Landscape Suitability ◽  
Kyasanur Forest Disease ◽  
The Western Ghats

Abstract Background Anthropogenic pressure in biodiversity hotspots is increasingly recognised as a major driver of the spillover and expansion of zoonotic disease. In the Western Ghats region of India, a devastating tick-borne zoonosis, Kyasanur Forest disease (KFD), has been expanding rapidly beyond its endemic range in recent decades. While it has been suggested that anthropogenic pressure in the form of land use changes that lead to the loss of native forest may be directly contributing to the expanding range of KFD, clear evidence has not yet established the association between forest loss and KFD risk. Methods The current study sought to investigate the relationship between KFD landscape suitability and both forest loss and mammalian species richness to inform its epidemiology and infection ecology. Forty-seven outbreaks of KFD between 1 January, 2012 and 30 June, 2019 were modelled as an inhomogeneous Poisson process. Results Both forest loss (relative risk (RR) = 1.83; 95% C.I. 1.33 – 2.51) and mammalian species richness (RR = 1.29; 95% C.I. 1.16 – 1.42) were strongly associated with increased risk of KFD. Conclusions These results provide the first evidence of a clear association between increasing forest loss and risk for KFD. Moreover, the findings also highlight the importance of forest loss in areas of high biodiversity. This evidence supports integrative approaches to public health that incorporate conservation strategies simultaneously protective of humans, animals, and the environment. Key messages The association between deforestation and KFD risk suggest potential benefit in leveraging conservation efforts in the service of public health.

scholarly journals A pigtailed macaque model of Kyasanur Forest disease virus and Alkhurma hemorrhagic disease virus pathogenesis

2021 ◽  
Vol 17 (12) ◽  
pp. e1009678
Author(s):  
Rebecca M. Broeckel ◽  
Friederike Feldmann ◽  
Kristin L. McNally ◽  
Abhilash I. Chiramel ◽  
Gail L. Sturdevant ◽  
...  
Keyword(s):  
Disease Virus ◽  
Human Disease ◽  
Gastrointestinal Symptoms ◽  
Macaca Nemestrina ◽  
Hemorrhagic Disease ◽  
Clotting Factors ◽  
Forest Disease ◽  
Elevated Liver Enzymes ◽  
Kyasanur Forest Disease ◽  
The Impact

Kyasanur Forest disease virus (KFDV) and the closely related Alkhurma hemorrhagic disease virus (AHFV) are emerging flaviviruses that cause severe viral hemorrhagic fevers in humans. Increasing geographical expansion and case numbers, particularly of KFDV in southwest India, class these viruses as a public health threat. Viral pathogenesis is not well understood and additional vaccines and antivirals are needed to effectively counter the impact of these viruses. However, current animal models of KFDV pathogenesis do not accurately reproduce viral tissue tropism or clinical outcomes observed in humans. Here, we show that pigtailed macaques (Macaca nemestrina) infected with KFDV or AHFV develop viremia that peaks 2 to 4 days following inoculation. Over the course of infection, animals developed lymphocytopenia, thrombocytopenia, and elevated liver enzymes. Infected animals exhibited hallmark signs of human disease characterized by a flushed appearance, piloerection, dehydration, loss of appetite, weakness, and hemorrhagic signs including epistaxis. Virus was commonly present in the gastrointestinal tract, consistent with human disease caused by KFDV and AHFV where gastrointestinal symptoms (hemorrhage, vomiting, diarrhea) are common. Importantly, RNAseq of whole blood revealed that KFDV downregulated gene expression of key clotting factors that was not observed during AHFV infection, consistent with increased severity of KFDV disease observed in this model. This work characterizes a nonhuman primate model for KFDV and AHFV that closely resembles human disease for further utilization in understanding host immunity and development of antiviral countermeasures.

scholarly journals Development of single step RT-PCR for detection of Kyasanur forest disease virus from clinical samples

Heliyon ◽  
2018 ◽  
Vol 4 (2) ◽  
pp. e00549 ◽  
Author(s):  
Gouri Chaubal ◽  
Prasad Sarkale ◽  
Pravin Kore ◽  
Pragya Yadav
Keyword(s):  
Disease Virus ◽  
Single Step ◽  
Clinical Samples ◽  
Rt Pcr ◽  
Forest Disease ◽  
Kyasanur Forest Disease

scholarly journals Kyasanur Forest disease virus non-mouse animal models: a pilot study

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
A. M. Nikiforuk ◽  
K. Tierny ◽  
T. A. Cutts ◽  
D. K. Kobasa ◽  
S. S. Theriault ◽  
...  
Keyword(s):  
Pilot Study ◽  
Animal Models ◽  
Disease Virus ◽  
Forest Disease ◽  
Kyasanur Forest Disease
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