Author: Shaia, Carl ; Bhatia, Bharti ; Hanley, Patrick W ; Rosenke, Rebecca ; Feldmann, Friederike ; Feldmann, Heinz ; Marzi, Andrea ; Tang-Huau, Tsing-Lee

Kyasanur Forest disease virus (KFDV) is an endemic arbovirus in western India mainly transmitted by hard ticks of the genus Haemaphysalis . KFDV causes Kyasanur Forest disease (KFD), a syndrome including fever, gastrointestinal symptoms, and hemorrhages. There are no approved treatments, and the efficacy of the only vaccine licensed in India has recently been questioned. Here, we studied the protective efficacy of a vesicular stomatitis virus (VSV)–based vaccine expressing the KFDV precursor membrane and envelope proteins (VSV-KFDV) in pigtailed macaques. VSV-KFDV vaccination was found to be safe and elicited strong humoral and cellular immune responses. A single-dose vaccination reduced KFDV loads and pathology and protected macaques from KFD-like disease. Furthermore, VSV-KFDV elicited cross-reactive neutralizing immune responses to Alkhurma hemorrhagic fever virus, a KFDV variant found in Saudi Arabia.

npj VaccinesQ1 · MEDICINE

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

Q1 · MEDICINE

ArticleOA

Author: Bhatia, Bharti ; Marzi, Andrea ; Haddock, Elaine ; Feldmann, Friederike ; Feldmann, Heinz ; Meade-White, Kimberly

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.

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Indication	Highest Phase	Country/Location	Organization	Date
Kyasanur Forest Disease	Preclinical	United States	National Institutes of Health	22 May 2023

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