Phase II safety and immunogenicity study of live chikungunya virus vaccine TSI-GSD-218.

Abstract

Abstract. We conducted a phase II, randomized, double-blind, placebo-controlled, safety and immunogenicity study of a serially passaged, plaque-purified live chikungunya (CHIK) vaccine in 73 healthy adult volunteers. Fiftynine volunteers were immunized one time subcutaneously with the CHIK vaccine and 14 were immunized with placebo (tissue culture fluid). Vaccinees were clinically evaluated intensively for one month, and had repeated blood draws for serological assays (50% plaque-reduction neutralization test) for one year. Except for transient arthralgia in five CHIK vaccinees, the number and severity of local and systemic reactions and abnormal laboratory tests after immunization were similar in CHIK vaccinees and placebo recipients. Fifty-seven (98%) of 58 evaluable CHIK vaccinees developed CHIK neutralizing antibody by day 28, and 85% of vaccinees remained seropositive at one year after immunization. No placebo recipients seroconverted. This promising live vaccine was safe, produced well-tolerated side effects, and was highly immunogenic.

Chikungunya fever: A re-emerging viral infection

“…No vaccine is currently available for use; however, phase II safety and immunogenicity study of live CHIK vaccine TSI-GSD-218 had been undertaken in Maryland. [38] Although there were indications that other alpha virus vaccines may interfere with the immune response of live CHIK vaccine, this was found to be highly immunogenic as neutralizing antibodies were detected in 85% of the volunteers after 12 months. Long-term follow-up studies would be needed to determine the durability of immune response.…”

“…The vaccine was found to be safe; it produced well-tolerated side-effects such as transient arthralgia in 8% of individuals. [38] Further results are awaited as this appears to be a promising vaccine for use in alpha virus naïve individuals. Until then, prevention and control activities are to be targeted at vector source reduction.…”

Chimeric Sindbis/eastern equine encephalitis vaccine candidates are highly attenuated and immunogenic in mice

“…The latter may be explain the residual reactogenicity of alphavirus vaccines that rely on point mutations that accumulate during cell passages, including attenuated strains of Chikungunya virus [23] and VEEV [24]; 2) the success of the chimeric flavivirus vaccines also argues for this approach [25]; 3) live-attenuated vaccines have advantages over other approaches (e.g. subunit and inactivated vaccines) of rapid and long-lasting immunity, including both cellular and humoral.…”

Recent progress on chikungunya virus research

“…A liveattenuated vaccine TSI-GSD-218 has also been advanced into phase II clinical trials. In a double-blind, randomized, placebo-controlled study of vaccine in 73 healthy adult volunteers, this vaccine was demonstrated to be safe and highly immunogenic, but associated with transient arthralgia in five vaccinees (Edelman et al, 2000).…”