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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-12-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-021-00416-2 |
| _version_ | 1797428726845145088 |
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| author | Bharti Bhatia Kimberly Meade-White Elaine Haddock Friederike Feldmann Andrea Marzi Heinz Feldmann |
| author_facet | Bharti Bhatia Kimberly Meade-White Elaine Haddock Friederike Feldmann Andrea Marzi Heinz Feldmann |
| author_sort | Bharti Bhatia |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T09:03:02Z |
| format | Article |
| id | doaj.art-48b8a551263b4477bb31c747b6f7a083 |
| institution | Directory Open Access Journal |
| issn | 2059-0105 |
| language | English |
| last_indexed | 2024-03-09T09:03:02Z |
| publishDate | 2021-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj.art-48b8a551263b4477bb31c747b6f7a0832023-12-02T11:03:15ZengNature Portfolionpj Vaccines2059-01052021-12-016111110.1038/s41541-021-00416-2A live-attenuated viral vector vaccine protects mice against lethal challenge with Kyasanur Forest disease virusBharti Bhatia0Kimberly Meade-White1Elaine Haddock2Friederike Feldmann3Andrea Marzi4Heinz Feldmann5Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthRocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthAbstract 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.https://doi.org/10.1038/s41541-021-00416-2 |
| spellingShingle | Bharti Bhatia Kimberly Meade-White Elaine Haddock Friederike Feldmann Andrea Marzi Heinz Feldmann A live-attenuated viral vector vaccine protects mice against lethal challenge with Kyasanur Forest disease virus npj Vaccines |
| title | A live-attenuated viral vector vaccine protects mice against lethal challenge with Kyasanur Forest disease virus |
| title_full | A live-attenuated viral vector vaccine protects mice against lethal challenge with Kyasanur Forest disease virus |
| title_fullStr | A live-attenuated viral vector vaccine protects mice against lethal challenge with Kyasanur Forest disease virus |
| title_full_unstemmed | A live-attenuated viral vector vaccine protects mice against lethal challenge with Kyasanur Forest disease virus |
| title_short | A live-attenuated viral vector vaccine protects mice against lethal challenge with Kyasanur Forest disease virus |
| title_sort | live attenuated viral vector vaccine protects mice against lethal challenge with kyasanur forest disease virus |
| url | https://doi.org/10.1038/s41541-021-00416-2 |
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