Crimean-Congo Hemorrhagic Fever Virus Replicon Particle Vaccine is Safe and Elicits Functional, Non-neutralizing Anti-nucleoprotein Antibodies and T Cell Activation in Rhesus Macaques.

Details

• Alternative Title:
  Antiviral Research, 2025, v. 233: Crimean-Congo Hemorrhagic Fever Virus Replicon Particle Vaccine is Safe and Elicits Functional, Non-neutralizing Anti-nucleoprotein Antibodies and T Cell Activation in Rhesus Macaques.
• Journal Article:
  Antiviral Research
• Personal Author:
  Kleymann, Alyssa ; Karaaslan, Elif ; Scholte, Florine E.M. ; Sorvillo, Teresa E. ; Welch, Stephen R. ; Bergeron, Éric ; Elser, Stephanie ; Almanzar-Jordan, Melvyn R. ; Velazquez, Eric ; Genzer, Sarah C. ; Jean, Sherrie M. ; Spiropoulou, Christina F. ; Spengler, Jessica R.
• Description:
  Advancement of vaccine candidates that demonstrate protective efficacy in screening studies necessitates detailed safety and immunogenicity investigations in pre-clinical models. A non-spreading Crimean-Congo hemorrhagic fever virus (CCHFV) viral replicon particle (VRP) vaccine was developed for single-dose administration to protect against disease. To date, several studies have supported safety, immunogenicity, and efficacy of the CCHF VRP in multiple highly sensitive murine models of lethal disease, but the VRP had yet to be evaluated in large animals. Here, we performed studies in non-human primates to further evaluate clinical utility of the VRP vaccine. Twelve adult male and female rhesus macaques were vaccinated intramuscularly and clinical monitoring was performed daily for 28 days. At 3, 7, 14, 21, and 28 days post vaccination, animals were sedated for more detailed clinical assessment; for quantification of vaccine presence in blood and mucosal samples; and for evaluation of hematology, plasma inflammatory markers, and immunogenicity. Consistent with findings in mice, vaccination was well tolerated, with no clinical alterations nor indication of vaccine spread or shedding. In addition, vaccination induced both humoral and cell-mediated responses, with immune profile and kinetics also corroborating data from small animal models. These studies provide key data in non-human primates further supporting development of the VRP for human clinical use.
• Content Notes:
  Author manuscript
• Subjects:
  • Animals
  • Macaca mulatta
  • Female
  • Hemorrhagic Fever Virus, Crimean-Congo
  • Antibodies, Viral
  • Male
  • T-Lymphocytes
  • Viral Vaccines
  • Hemorrhagic Fever, Crimean
  • Lymphocyte Activation
  More +
• Keywords:
  • Crimean-Congo hemorrhagic fever virus
  • Vaccine
  • Safety
  • Immune response
  • Non-human primate
• Source:
  Antiviral Research, 2025, v. 233
• DOI:
  https://doi.org/10.1016/j.antiviral.2024.106045
• ISSN:
  0166-3542 ; 1872-9096
• Pubmed ID:
  39626793
• Pubmed Central ID:
  PMC11871586
• Document Type:
  Text
• Funding:
  CC999999/ImCDC/Intramural CDC HHSUnited States/ ; R01 AI151006/AI/NIAID NIH HHSUnited States/
• Genre:
  Journal Article
• Pages in Document:
  106045 (18 pdf pages)
• Volume:
  233
• Download URL:
  https://stacks.cdc.gov/view/cdc/261891/cdc_261891_DS1.pdf
• File Type:
  [PDF - 1.89 MB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:4dc388c002af4aa9ba45e1b415cf42f52cc597b95019b95e113ed15c083a117abf4d9caa4a72d7e608b53dd3997a82eddac9cd2a922ae32d1d571aa3b7659073