Novel delivery of a live-attenuated chikungunya virus vaccine candidate (#84)
Chikungunya virus (CHIKV) is an alphavirus that causes outbreaks of chikungunya, a mosquito-borne viral disease. The disease causes highly debilitating arthritis that can persist for months or years. Alphaviruses related to CHIKV, e.g. Ross River virus (endemic in Australia & Pacific) cause similar incapacitating musculoskeletal disease. There are no CHIKV antivirals, nor is there a licensed vaccine. We have developed and a live-attenuated CHIKV vaccine candidate, CHIKV-NoLS. CHIKV-NoLS immunised mice are protected from CHIKV infection. Additionally, this vaccine shows cross-protection against Ross River virus. A live-attenuated vaccine is a desirable means of disease prevention due to ease of production, low cost and avoidance of multiple boosters. However, propagation of CHIKV-NoLS is limited by its attenuated replication. Removing this bottleneck in production would greatly benefit CHIKV-NoLS development. The investigation described here aims to bypass in vitro propagation by using a novel delivery method, allowing for in vivo inoculation. Results suggest delivery of CHIKV-NoLS using this methodology in mice elicits de novo CHIKV-NoLS particle production in vivo. Mice immunised using this strategy develop long-term protection from CHIKV disease.