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Published on: December 23, 2016
Chikungunya virus infection in Cynomolgus macaques following Intradermal and aerosol exposure
Chris M Cirimotich1, Eric M Vela2,3, Jennifer Garver2
1Battelle, West Jefferson, OH, 43162, USA. CirimotichC@Battelle.Org.
Background:
Chikungunya virus (CHIKV) is transmitted via mosquito bite and potentially by aerosol, causing chikungunya fever and arthritic disease in humans. There are currently no licensed vaccines or antiviral therapeutics to protect against CHIKV infection in humans. Animal models recapitulating human disease, especially for transmission by aerosol, are needed for licensure of such medical countermeasures.
Methods:
Cynomolgus macaques (CMs) were challenged by intradermal (ID) inoculation or exposure to an aerosol containing CHIKV Ross strain at different target infectious doses (103-107 plaque forming units (PFU)). The clinical and virologic courses of disease were monitored up to 14 days post-exposure.
Results:
ID infection of CMs led to overt clinical disease, detectable viremia, and increased blood markers of liver damage. Animals challenged by aerosol exhibited viremia and increased liver damage biomarkers with minimal observed clinical disease. All animals survived CHIKV challenge.
Conclusions:
We have described CHIKV infection in CMs following ID inoculation and, for the first time, infection by aerosol. Based on limited reported cases in the published literature, the aerosol model recapitulates the virologic findings of human infection via this route. The results of this study provide additional evidence for the potential use of CMs as a model for evaluating medical countermeasures against CHIKV.
Insights
Cynomolgus macaques exposed to Chikungunya virus (CHIKV) via aerosol or injection developed infection. This study establishes a valuable animal model for testing new CHIKV medical countermeasures.
Area of Science:
- Virology
- Infectious Diseases
- Immunology
Background:
- Chikungunya virus (CHIKV) causes fever and arthritis, with no current human vaccines or treatments.
- Effective animal models are crucial for developing medical countermeasures against CHIKV, particularly for aerosol transmission.
- Current animal models do not fully replicate human CHIKV infection, especially via aerosol routes.
Purpose of the Study:
- To establish and characterize a Cynomolgus macaque (CM) model for Chikungunya virus (CHIKV) infection via aerosol and intradermal (ID) inoculation.
- To assess the clinical and virologic outcomes of CHIKV infection in CMs following different exposure routes.
- To provide a suitable animal model for evaluating the efficacy of medical countermeasures against CHIKV.
Main Methods:
- Cynomolgus macaques (CMs) were inoculated intradermally (ID) or exposed to aerosolized CHIKV Ross strain.
- Various infectious doses (10^3-10^7 PFU) were used for challenge.
- Clinical signs, viremia, and liver damage biomarkers were monitored for 14 days post-exposure.
Main Results:
- Intradermal (ID) CHIKV inoculation caused overt clinical disease, viremia, and elevated liver damage markers.
- Aerosol CHIKV exposure resulted in viremia and increased liver damage biomarkers with minimal clinical signs.
- All challenged CMs survived the CHIKV infection.
Conclusions:
- This study successfully modeled CHIKV infection in CMs via both ID inoculation and aerosol exposure.
- The aerosol model closely mimics virologic findings of human CHIKV infection through this route.
- CMs serve as a promising animal model for evaluating medical countermeasures against CHIKV infections.
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