TY - JOUR
T1 - Vesicular Stomatitis Virus-Based Vaccine Protects Mice against Crimean-Congo Hemorrhagic Fever
AU - Rodriguez, Sergio E.
AU - Cross, Robert W.
AU - Fenton, Karla
AU - Bente, Dennis A.
AU - Mire, Chad
AU - Geisbert, Thomas W.
N1 - Funding Information:
The authors would like to thank the UTMB Molecular Genomics Core, Assay Development Core (for deep sequencing support), Animal Resource Center (for handling and husbandry of laboratory animals), Electron Microscopy Laboratory Core (specifically, Vsevolod Popov and Julie Wen for electron microscopy support), and Natalie Dobias for immunohistochemistry support. We gratefully acknowledge Krystle Agans, Katharina Schmitz, Gordon Wong, Auja Smith, Angel Padilla, Emily Mantlo, Teresa Sorvillo, Courtney Woolsey, Corey Fulton, Stephanie Foster, Maria Cajimat, Benjamin Satterfield, and Daniel Deer, Viktoriya Borisevich, Joan Geisbert, for various in vitro and in vivo technical guidance and support throughout the project. We thank Thomas Ksiazek, Michael Whitt, Jeroen Kortekaas, and Éric Bergeron for the gifts of vector/insert plasmids, reagents, cell lines, and virus strains. Additionally, we further thank Éric Bergeron for fruitful discussions and unpublished data regarding CCHFV-GPC reagents and Thomas Ksiazek for ELISA development discussions. This research was conducted by S.E.R. in partial fulfillment of the requirements for a Ph.D. from the University of Texas Medical Branch, Galveston, Texas, USA. Funding and support was provided by the UTMB Department of Microbiology and Immunology to T.W.G.
Publisher Copyright:
© 2019, The Author(s).
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Crimean-Congo hemorrhagic fever virus (CCHFV), a tick-borne bunyavirus, can cause a life-threatening hemorrhagic syndrome in humans but not in its animal host. The virus is widely distributed throughout southeastern Europe, the Middle East, Africa, and Asia. Disease management has proven difficult and there are no broadly licensed vaccines or therapeutics. Recombinant vesicular stomatitis viruses (rVSV) expressing foreign glycoproteins (GP) have shown promise as experimental vaccines for several viral hemorrhagic fevers. Here, we developed and assessed a replication competent rVSV vector expressing the CCHFV glycoprotein precursor (GPC), which encodes CCHFV structural glycoproteins. This construct drives strong expression of CCHFV-GP, in vitro. Using these vectors, we vaccinated STAT-1 knock-out mice, an animal model for CCHFV. The vector was tolerated and 100% efficacious against challenge from a clinical strain of CCHFV. Anti-CCHFV-GP IgG and neutralizing antibody titers were observed in surviving animals. This study demonstrates that a rVSV expressing only the CCHFV-GP has the potential to serve as a replication competent vaccine platform against CCHF infections.
AB - Crimean-Congo hemorrhagic fever virus (CCHFV), a tick-borne bunyavirus, can cause a life-threatening hemorrhagic syndrome in humans but not in its animal host. The virus is widely distributed throughout southeastern Europe, the Middle East, Africa, and Asia. Disease management has proven difficult and there are no broadly licensed vaccines or therapeutics. Recombinant vesicular stomatitis viruses (rVSV) expressing foreign glycoproteins (GP) have shown promise as experimental vaccines for several viral hemorrhagic fevers. Here, we developed and assessed a replication competent rVSV vector expressing the CCHFV glycoprotein precursor (GPC), which encodes CCHFV structural glycoproteins. This construct drives strong expression of CCHFV-GP, in vitro. Using these vectors, we vaccinated STAT-1 knock-out mice, an animal model for CCHFV. The vector was tolerated and 100% efficacious against challenge from a clinical strain of CCHFV. Anti-CCHFV-GP IgG and neutralizing antibody titers were observed in surviving animals. This study demonstrates that a rVSV expressing only the CCHFV-GP has the potential to serve as a replication competent vaccine platform against CCHF infections.
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U2 - 10.1038/s41598-019-44210-6
DO - 10.1038/s41598-019-44210-6
M3 - Article
C2 - 31123310
AN - SCOPUS:85066839986
VL - 9
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 7755
ER -