title: Chikungunya vaccine candidate is highly attenuated and protects nonhuman primates against telemetrically monitored disease following a single dose.
abstract: 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.
authors.affiliation: Division of Microbiology, Tulane National Primate Research Center, Covington, Louisiana.
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Roy
authors.affiliation: Institute for Human Infections and Immunity, Sealy Center for Vaccine Development Department of Pathology, University of Texas Medical Branch, Galveston, Texas.
authors.forename: A Paige
authors.initials: AP
authors.lastname: Adams
authors.affiliation: Institute for Human Infections and Immunity, Sealy Center for Vaccine Development Department of Pathology, University of Texas Medical Branch, Galveston, Texas.
authors.forename: Eryu
authors.initials: E
authors.lastname: Wang
authors.affiliation: Institute for Human Infections and Immunity, Sealy Center for Vaccine Development Department of Pathology, University of Texas Medical Branch, Galveston, Texas.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Plante
authors.affiliation: Institute for Human Infections and Immunity, Sealy Center for Vaccine Development Department of Pathology, University of Texas Medical Branch, Galveston, Texas.
authors.forename: Rodion
authors.initials: R
authors.lastname: Gorchakov
authors.affiliation: Institute for Human Infections and Immunity, Sealy Center for Vaccine Development Department of Pathology, University of Texas Medical Branch, Galveston, Texas.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Seymour
authors.affiliation: Division of Veterinary Medicine, Tulane National Primate Research Center, Covington, Louisiana.
authors.forename: Heather
authors.initials: H
authors.lastname: Vinet-Oliphant
authors.affiliation: Institute for Human Infections and Immunity, Sealy Center for Vaccine Development Department of Pathology, University of Texas Medical Branch, Galveston, Texas.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Weaver
mesh_terms: D018354:Alphavirus Infections / Q000517:prevention & control*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D065632:Chikungunya Fever; D002646:Chikungunya virus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008252:Macaca fascicularis / Q000276:immunology* / Q000821:virology; D013686:Telemetry; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines
keywords: Chikungunya virus; nonhuman primates; viral vaccine