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

Abstract

Kyasanur 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.

Distinct VSV-based Nipah virus vaccines expressing either glycoprotein G or fusion protein F provide homologous and heterologous protection in a nonhuman primate model

“…VeroE6 cells were inoculated with a MOI of 0.001 of the three vaccines and replication was followed over time. Although the VSV-EBOV replicates less efficiently than recombinant wild type VSV, 22 replication kinetics were remarkably similar between VSV-EBOV, VSV-NiVG and VSV-NiVF and all three viruses reached similar peak titers at 72 hpi ( Fig. 1 b).…”

Single-dose VSV-based vaccine protects against Kyasanur Forest disease in nonhuman primates

“…Here, we report the development of a live-attenuated VSV-based KFDV vaccine that was safe, elicited strong humoral and cellular immune responses, and provided solid protection against KFD-like disease in two animal disease models, the mouse ( 26 ) and the pigtailed macaque (this study). This completes the basic preclinical development and allows VSV-KFDV to progress toward clinical development.…”

“…Recently, we developed two versions of a KFDV vaccine candidate based on the vesicular stomatitis virus Ebola vaccine (VSV-EBOV) ( 25 ) additionally expressing the KFDV prM and E proteins (VSV-KFDV) ( 26 ). Both live-attenuated recombinant VSV vectors, which differ only in their EBOV glycoprotein (GP) gene (full-length versus truncated), provided strong protection against disease in BALB/c mice challenged with a lethal dose of KFDV.…”

“…Both live-attenuated recombinant VSV vectors, which differ only in their EBOV glycoprotein (GP) gene (full-length versus truncated), provided strong protection against disease in BALB/c mice challenged with a lethal dose of KFDV. Protection by these VSV-based vaccines was most likely mediated through antibodies as evidenced by passive transfer studies ( 26 ).…”

Sociodemographic factors associated with Kyasanur forest disease in India - a retrospective study

“…Previous research on KFD has significantly advanced our knowledge of the genetic structure of the virus [12] , the clinical characteristics of both the virus and the disease [5] , and information related to vaccines [13] . However, despite these contributions, since the disease's discovery, much of the research on KFD has predominantly concentrated on its virology and epidemiology, with limited attention given to investigating the socioeconomic determinants and risk factors associated with the disease in India [14] .…”