Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 209, Issue 12, Pages 1891-1899Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiu014
Keywords
Chikungunya virus; nonhuman primates; viral vaccine
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Funding
- National Institute of Allergy and Infectious Disease (NIAID) through the Western Regional Center of Excellence for Biodefense and Emerging Infectious Disease Research (WRCE), National Institutes of Health (NIH) [U54 AI057156]
- NIH [AI077796, AI007536]
- NIH/OD grant [OD-011104-51]
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Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes major epidemics of rash, fever, and debilitating arthritis. Currently, there are no vaccines or antivirals available for prevention or treatment. We therefore generated 2 live-attenuated vaccine candidates based on the insertion of a picornavirus internal ribosome entry site (IRES) sequence into the genome of CHIKV. Vaccination of cynomolgus macaques with a single dose of either vaccine produced no signs of disease but was highly immunogenic. After challenge with a subcutaneous inoculation of wild-type CHIKV, both vaccine candidates prevented the development of detectable viremia. Protected animals also exhibited no significant changes in core body temperature or cardiovascular rhythm, whereas sham-vaccinated animals showed hyperthermia, followed by sustained hypothermia, as well as significant changes in heart rate. These CHIKV/IRES vaccine candidates appear to be safe and efficacious, supporting their strong potential as human vaccines to protect against CHIKV infection and reduce transmission and further spread.
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