A replicating RNA vaccine confers protection against Crimean-Congo hemorrhagic fever in cynomolgus macaquesResearch in context

Summary: Background: Crimean-Congo hemorrhagic fever is a tick-borne febrile illness with wide geographic distribution. In recent years the geographic range of CCHFV and its tick vector have increased, placing an increasing number of people at risk of CCHFV infection. Currently there are no widely...

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Main Authors: David W. Hawman, Shanna Leventhal, Kimberly Meade-White, William Graham, Karen Gaffney, Amit Khandhar, Justin Murray, Jessy Prado-Smith, Carl Shaia, Greg Saturday, Henry Buda, Lenny Moise, Jesse Erasmus, Heinz Feldmann
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Language:English
Published: Elsevier 2025-05-01
Series:EBioMedicine
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Online Access:http://www.sciencedirect.com/science/article/pii/S2352396425001422
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author David W. Hawman
Shanna Leventhal
Kimberly Meade-White
William Graham
Karen Gaffney
Amit Khandhar
Justin Murray
Jessy Prado-Smith
Carl Shaia
Greg Saturday
Henry Buda
Lenny Moise
Jesse Erasmus
Heinz Feldmann
author_facet David W. Hawman
Shanna Leventhal
Kimberly Meade-White
William Graham
Karen Gaffney
Amit Khandhar
Justin Murray
Jessy Prado-Smith
Carl Shaia
Greg Saturday
Henry Buda
Lenny Moise
Jesse Erasmus
Heinz Feldmann
author_sort David W. Hawman
collection DOAJ
description Summary: Background: Crimean-Congo hemorrhagic fever is a tick-borne febrile illness with wide geographic distribution. In recent years the geographic range of CCHFV and its tick vector have increased, placing an increasing number of people at risk of CCHFV infection. Currently there are no widely available vaccines and although the World Health Organization recommends ribavirin for treatment, its efficacy is unclear. Vaccines are critically needed for CCHFV. Methods: Here we evaluated a promising replicating RNA vaccine for CCHFV in a Cynomolgus macaque model of disease. Findings: In primed and boosted macaques, we found that our replicating RNA vaccine expressing the CCHFV nucleoprotein (repNP) was highly immunogenic, eliciting a robust non-neutralizing antibody response that conferred significant protection against CCHFV challenge. Macaques receiving a single repNP vaccination were partially protected against CCHFV challenge. Interpretation: Our data demonstrate that our repNP vaccine and NP-specific antibody can protect against CCHFV in non-human primates. Funding: This study was supported by the Intramural Research Program of the NIAID/NIH and the Medical CBRN Defense Consortium grant #MCDC2204-011.
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spelling doaj-art-faefe9ba0eb648d186f86c3c02003e372025-08-20T02:11:55ZengElsevierEBioMedicine2352-39642025-05-0111510569810.1016/j.ebiom.2025.105698A replicating RNA vaccine confers protection against Crimean-Congo hemorrhagic fever in cynomolgus macaquesResearch in contextDavid W. Hawman0Shanna Leventhal1Kimberly Meade-White2William Graham3Karen Gaffney4Amit Khandhar5Justin Murray6Jessy Prado-Smith7Carl Shaia8Greg Saturday9Henry Buda10Lenny Moise11Jesse Erasmus12Heinz Feldmann13Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT, 59840, USA; HDT Bio, Seattle, WA, 98109, USA; Corresponding author. HDT Bio, Seattle, WA, 98109, USA.Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT, 59840, USALaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT, 59840, USASeromyx Systems, Woburn, MA, 01801, USAHDT Bio, Seattle, WA, 98109, USAHDT Bio, Seattle, WA, 98109, USALaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT, 59840, USARocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT, 59840, USARocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT, 59840, USARocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT, 59840, USASeromyx Systems, Woburn, MA, 01801, USASeromyx Systems, Woburn, MA, 01801, USAHDT Bio, Seattle, WA, 98109, USALaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT, 59840, USA; Corresponding author.Summary: Background: Crimean-Congo hemorrhagic fever is a tick-borne febrile illness with wide geographic distribution. In recent years the geographic range of CCHFV and its tick vector have increased, placing an increasing number of people at risk of CCHFV infection. Currently there are no widely available vaccines and although the World Health Organization recommends ribavirin for treatment, its efficacy is unclear. Vaccines are critically needed for CCHFV. Methods: Here we evaluated a promising replicating RNA vaccine for CCHFV in a Cynomolgus macaque model of disease. Findings: In primed and boosted macaques, we found that our replicating RNA vaccine expressing the CCHFV nucleoprotein (repNP) was highly immunogenic, eliciting a robust non-neutralizing antibody response that conferred significant protection against CCHFV challenge. Macaques receiving a single repNP vaccination were partially protected against CCHFV challenge. Interpretation: Our data demonstrate that our repNP vaccine and NP-specific antibody can protect against CCHFV in non-human primates. Funding: This study was supported by the Intramural Research Program of the NIAID/NIH and the Medical CBRN Defense Consortium grant #MCDC2204-011.http://www.sciencedirect.com/science/article/pii/S2352396425001422Crimean-CongoAntibodyVaccineRNA vaccineNon-human primates
spellingShingle David W. Hawman
Shanna Leventhal
Kimberly Meade-White
William Graham
Karen Gaffney
Amit Khandhar
Justin Murray
Jessy Prado-Smith
Carl Shaia
Greg Saturday
Henry Buda
Lenny Moise
Jesse Erasmus
Heinz Feldmann
A replicating RNA vaccine confers protection against Crimean-Congo hemorrhagic fever in cynomolgus macaquesResearch in context
EBioMedicine
Crimean-Congo
Antibody
Vaccine
RNA vaccine
Non-human primates
title A replicating RNA vaccine confers protection against Crimean-Congo hemorrhagic fever in cynomolgus macaquesResearch in context
title_full A replicating RNA vaccine confers protection against Crimean-Congo hemorrhagic fever in cynomolgus macaquesResearch in context
title_fullStr A replicating RNA vaccine confers protection against Crimean-Congo hemorrhagic fever in cynomolgus macaquesResearch in context
title_full_unstemmed A replicating RNA vaccine confers protection against Crimean-Congo hemorrhagic fever in cynomolgus macaquesResearch in context
title_short A replicating RNA vaccine confers protection against Crimean-Congo hemorrhagic fever in cynomolgus macaquesResearch in context
title_sort replicating rna vaccine confers protection against crimean congo hemorrhagic fever in cynomolgus macaquesresearch in context
topic Crimean-Congo
Antibody
Vaccine
RNA vaccine
Non-human primates
url http://www.sciencedirect.com/science/article/pii/S2352396425001422
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