Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes
explosive outbreaks of febrile illness associated with
rash, and painful
arthralgia. The CHIK
vaccine strain 181/clone25 (181/25) developed by the United States Army Medical Research Institute of
Infectious Diseases (USAMRIID) was shown to be well-tolerated and highly immunogenic in phase I and II clinical trials although it induced transient
arthralgia in some healthy adult volunteers. In an attempt to better understand the host factors that are involved in the attenuating phenotype of CHIK 181/25
vaccine virus we conducted studies in
interferon (IFN)-compromised mice and also evaluated its immunogenic potential and protective capacity.
Infection of AG129 mice (defective in IFN-α/β and IFN-γ receptor signaling) with CHIK 181/25 resulted in rapid mortality within 3-4 days. In contrast, all infected A129 mice (defective in IFN-α/β receptor signaling) survived with temporary morbidity characterized by ruffled appearance and
body weight loss. A129 heterozygote mice that retain partial IFN-α/β receptor signaling activity remained healthy.
Infection of A129 mice with CHIK 181/25 induced significant levels of IFN-γ and
IL-12 while the inflammatory
cytokines, TNFα and
IL-6 remained low. A single administration of the CHIK 181/25
vaccine provided both short-term and long-term protection (38 days and 247 days post-prime, respectively) against challenge with wt CHIKV-La Reunion (CHIKV-LR). This protection was at least partially mediated by
antibodies since passively transferred immune serum protected both A129 and AG129 mice from wt CHIKV-LR and 181/25 virus challenge. Overall, these data highlight the importance of IFNs in controlling CHIK 181/25
vaccine and demonstrate the ability of this
vaccine to elicit
neutralizing antibody responses that confer short-and long-term protection against wt CHIKV-LR challenge.