Limited tissue persistence confirms attenuation of live-attenuated chikungunya vaccine VLA1553 in non-human primates

Abstract Chronic chikungunya disease is caused by the mosquito-borne chikungunya virus (CHIKV) induced by viral persistence in target tissues. To investigate the risk of viral persistence of the approved live-attenuated vaccine IXCHIQ ® (VLA1553), cynomolgus macaques received a 100-fold higher dose than the approved dose for IXCHIQ ® or wild-type CHIKV. In VLA1553-treated NHPs, fever was transient, coinciding with peak viremia, with no significant virus detected in tissues except for immune organs. WT CHIKV-treated NHPs developed fever persisting for several days with higher peak viremias, and virus was consistently detected in tissues at higher levels than in VLA1553-treated animals. Additionally, WT CHIKV-treated NHPs showed more CHIKV in saliva and vaginal fluid, lymphocytopenia, increased liver enzymes and plasma prostaglandin E 2 , and higher expression of pro-inflammatory cytokines and chemokines associated with WT CHIKV disease than VLA1553-treated animals. This study demonstrated attenuation of vaccine strain VLA1553, with no critical observations in non-human primates (NHPs) following administration of a high dose.