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.

Attenuated and vectored vaccines protect nonhuman primates against Chikungunya virus

“…To evaluate whether the vaccinated animals in this study were protected from CHIKV infection, we determined the plasma viral load immediately after challenge with a dose of CHIKV close to 100 times the 50% Animal Infectious Dose (AID 50 ). LR-CHIKV infection of cynomolgus macaques typically results in plasma viremia that peaks at day 2-3 after challenge (13,15). Consistent with this, we found that all control animals that had received only saline displayed high peak viremia that declined, reaching undetectable levels by day 10 after challenge ( Figure 6A).…”

Chikungunya virus: epidemiology, replication, disease mechanisms, and prospective intervention strategies

“…This modification decreases the expression of viral structural proteins (184,185), which attenuates replication in mammalian cells and prevents replication in mosquito cells, as the IRES is not functional in insect cells (184). The CHIKV/IRES vaccine is safe, highly immunogenic, and efficacious in mice and NHPs (184,185), while remaining attenuated (186). nature of CHIKV disease and its associated economic burden are important considerations for the development of specific treatments.…”

Recent progress on chikungunya virus research

“…More CHIKV vaccine candidates are in preclinical studies (Schwameis et al, 2016). CHIKV-IRES vaccine, achieved by inserting a picornavirus internal ribosome entry site (IRES) into the CHIKV genome, exhibited high immunogenicity and produced no signs of disease in nonhuman primates (Roy et al, 2014). DNA vaccine utilizes a plasmid encoding CHIKV structure protein or full-length sequence from an attenuated CHIKV clone 181/25 was shown to activate immune responses in mice, without causing joint swelling, and induced long-lived protective antibodies (Hallengard et al, 2014;Tretyakova et al, 2014).…”