Vesicular Stomatitis Virus-Based Vaccine Protects Mice against Crimean-Congo Hemorrhagic Fever

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 a...

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Vydané v:Scientific reports Ročník 9; číslo 1; s. 7755 - 13
Hlavní autori: Rodriguez, Sergio E., Cross, Robert W., Fenton, Karla A., Bente, Dennis A., Mire, Chad E., Geisbert, Thomas W.
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: London Nature Publishing Group UK 23.05.2019
Nature Publishing Group
Nature Portfolio
Predmet:
13
631/326/590
631/326/596
64
Animal models
Animals
Antibodies, Neutralizing - immunology
Antibodies, Viral - immunology
Cell Line
Crimean hemorrhagic fever
Disease Models, Animal
Epidemics
Expression vectors
Female
Glycoproteins
Glycoproteins - immunology
Hemorrhage
Hemorrhagic Fever Virus, Crimean-Congo - immunology
Hemorrhagic Fever Virus, Crimean-Congo - pathogenicity
Hemorrhagic Fever, Crimean - immunology
Hemorrhagic Fever, Crimean - prevention & control
Humanities and Social Sciences
Immunoglobulin G
Mice
Mice, Knockout
multidisciplinary
Replication
Science
Science (multidisciplinary)
Stat1 protein
STAT1 Transcription Factor - genetics
Stomatitis
Vaccination - methods
Vaccines
Vaccines - immunology
Vesicular stomatitis Indiana virus - immunology
Vesicular stomatitis Indiana virus - pathogenicity
Vesiculovirus - immunology
Viruses
ISSN:2045-2322, 2045-2322
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Abstract 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.
AbstractList 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.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.
Abstract 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.
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.
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.
ArticleNumber 7755
Author Mire, Chad E.
Cross, Robert W.
Rodriguez, Sergio E.
Geisbert, Thomas W.
Fenton, Karla A.
Bente, Dennis A.
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  surname: Cross
  fullname: Cross, Robert W.
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  givenname: Dennis A.
  orcidid: 0000-0002-5150-7368
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  givenname: Thomas W.
  surname: Geisbert
  fullname: Geisbert, Thomas W.
  email: twgeisbe@utmb.edu
  organization: Galveston National Laboratory, University of Texas Medical Branch, Department of Microbiology & Immunology, University of Texas Medical Branch
BackLink https://www.ncbi.nlm.nih.gov/pubmed/31123310$$D View this record in MEDLINE/PubMed
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LawsonNDStillmanEAWhittMARoseJKRecombinant vesicular stomatitis viruses fromDNA. Proc. Natl. Acad. Sci.199592447744811995PNAS...92.4477L1:CAS:528:DyaK2MXls1aks7c%3D10.1073/pnas.92.10.4477
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Snippet 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....
Abstract Crimean-Congo hemorrhagic fever virus (CCHFV), a tick-borne bunyavirus, can cause a life-threatening hemorrhagic syndrome in humans but not in its...
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StartPage 7755
SubjectTerms 13
631/326/590
631/326/596
64
Animal models
Animals
Antibodies, Neutralizing - immunology
Antibodies, Viral - immunology
Cell Line
Crimean hemorrhagic fever
Disease Models, Animal
Epidemics
Expression vectors
Female
Glycoproteins
Glycoproteins - immunology
Hemorrhage
Hemorrhagic Fever Virus, Crimean-Congo - immunology
Hemorrhagic Fever Virus, Crimean-Congo - pathogenicity
Hemorrhagic Fever, Crimean - immunology
Hemorrhagic Fever, Crimean - prevention & control
Humanities and Social Sciences
Immunoglobulin G
Mice
Mice, Knockout
multidisciplinary
Replication
Science
Science (multidisciplinary)
Stat1 protein
STAT1 Transcription Factor - genetics
Stomatitis
Vaccination - methods
Vaccines
Vaccines - immunology
Vesicular stomatitis Indiana virus - immunology
Vesicular stomatitis Indiana virus - pathogenicity
Vesiculovirus - immunology
Viruses
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Title Vesicular Stomatitis Virus-Based Vaccine Protects Mice against Crimean-Congo Hemorrhagic Fever
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