title: Crimean-Congo Hemorrhagic Fever Virus Subunit Vaccines Induce High Levels of Neutralizing Antibodies But No Protection in STAT1 Knockout Mice.
abstract: Crimean-Congo hemorrhagic fever virus is a tick-borne bunyavirus of the Nairovirus genus that causes hemorrhagic fever in humans with high case fatality. Here, we report the development of subunit vaccines and their efficacy in signal transducer and activator of transcription 1 (STAT1) knockout mice. Ectodomains of the structural glycoproteins Gn and Gc were produced using a Drosophila insect cell-based expression system. A single vaccination of STAT129 mice with adjuvanted Gn or Gc ectodomains induced neutralizing antibody responses, which were boosted by a second vaccination. Despite these antibody responses, mice were not protected from a CCHFV challenge infection. These results suggest that neutralizing antibodies against CCHFV do not correlate with protection of STAT1 knockout mice.
authors.affiliation: 1 Department of Virology, Central Veterinary Institute (CVI-Lelystad), part of Wageningen University and Research Centre , Lelystad, The Netherlands .
authors.forename: Jeroen
authors.initials: J
authors.lastname: Kortekaas
authors.affiliation: 1 Department of Virology, Central Veterinary Institute (CVI-Lelystad), part of Wageningen University and Research Centre , Lelystad, The Netherlands .
authors.forename: Rianka P M
authors.initials: RP
authors.lastname: Vloet
authors.affiliation: 2 Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, Texas.|3 Galveston National Laboratory , Galveston, Texas.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: McAuley
authors.affiliation: 2 Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, Texas.|3 Galveston National Laboratory , Galveston, Texas.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Shen
authors.affiliation: 4 Department of Infectious Diseases and Immunology, Virology Division, Faculty of Veterinary Medicine, Utrecht University , Utrecht, The Netherlands .
authors.forename: Berend Jan
authors.initials: BJ
authors.lastname: Bosch
authors.affiliation: 4 Department of Infectious Diseases and Immunology, Virology Division, Faculty of Veterinary Medicine, Utrecht University , Utrecht, The Netherlands .
authors.forename: Laura
authors.initials: L
authors.lastname: de Vries
authors.affiliation: 1 Department of Virology, Central Veterinary Institute (CVI-Lelystad), part of Wageningen University and Research Centre , Lelystad, The Netherlands .|4 Department of Infectious Diseases and Immunology, Virology Division, Faculty of Veterinary Medicine, Utrecht University , Utrecht, The Netherlands .
authors.forename: Rob J M
authors.initials: RJ
authors.lastname: Moormann
authors.affiliation: 2 Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, Texas.|3 Galveston National Laboratory , Galveston, Texas.
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Bente
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing; D004195:Disease Models, Animal; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000737:chemistry / Q000276:immunology; D003225:Hemorrhagic Fever Virus, Crimean-Congo / Q000276:immunology*; D006479:Hemorrhagic Fever, Crimean / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D050794:STAT1 Transcription Factor / Q000235:genetics; D014611:Vaccination; D022223:Vaccines, Subunit; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D006023:Glycoproteins; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D022223:Vaccines, Subunit; D014765:Viral Vaccines
keywords: Bunyavirus; Crimean–Congo hemorrhagic fever virus; Gc; Gn; Nairovirus; Neutralizing antibodies; STAT1; STAT129; Vaccine