Simultaneous injection of two LD-TDV doses was shown to have the potential to improve seroconversion rates to serotypes 1 and 2, and to increase serotype 2 antibody titers. A primary dose of LD-TDV administered by PharmaJet was shown to induce more rapid seroconversion to serotypes 1, 2, and 3 compared with administration by needle-syringe (ClinicalTrials.gov: NCT01765426).

Takeda has developed a live-attenuated dengue tetravalent vaccine candidate (TAK-003) which has been shown to be immunogenic with acceptable reactogenicity in phase 1 trials. In agreement with World Health Organization prequalification requirements for dengue vaccines, Takeda has manufactured a lyophilized formulation of TAK-003 that allows stable storage at +2°C to +8°C. This randomized, double-blind, phase 2 study (NCT02193087) was performed in 1002 healthy dengue-naïve adults, 18-49 years of age, across seven centers in the USA to compare the safety and immunogenicity of one or two doses of a lyophilized TAK-003 formulation with the liquid TAK-003 formulation used in previous phase 1 studies. The primary objective was to show immunologic equivalence in terms of geometric mean titers (GMT) of neutralizing antibodies to the four dengue serotypes one month after one dose of the lyophilized and liquid formulations. Secondary assessments were of safety and seropositivity rates, including after a second dose. The primary endpoint was not met, because immunologic equivalence after one dose was only shown for the DENV-2 serotype. Nonetheless, GMTs and seropositivity rates to all four serotypes were achieved with all formulations after two doses and are in line with what was observed in previous studies. Additionally, in view of the acceptable reactogenicity, with no vaccine-related serious adverse events reported, these data support continuing further clinical development of the lyophilized TAK-003 formulation.

Background We report long-term safety and immunogenicity of Takeda’s tetravalent dengue vaccine candidate (TAK-003) in healthy children and adults living in dengue-endemic areas in Puerto Rico, Columbia, Singapore, and Thailand (NCT01511250). Methods In part 1 of this phase 2, randomized, placebo-controlled trial we sequentially enrolled 1.5–45 year-olds (N=148) into four age-descending groups, randomized 2:1 to receive two doses of TAK-003 or placebo 90 days apart. In part 2, 1–11 year-olds (N=212) were enrolled and randomized 3:1 to TAK-003 or placebo groups. We assessed neutralizing antibody titers for the four dengue serotypes (DENV) up to Month 36 in part 1, and symptomatic dengue and serious adverse events (SAEs) up to Month 36 in both parts. Results At Month 36, seropositivity rates were 97.3%, 98.7%, 88.0% and 56.0% for DENV-1, -2, -3 and -4, respectively. Seropositivity rates varied significantly for DENV-4 according to serostatus at baseline (89.5% in seropositives versus 21.6% in seronegatives). No vaccine-related SAEs were reported. Conclusion The trial demonstrated persistence of neutralizing antibody titers against TAK-003 over three years in children and adults living in dengue endemic countries, with limited contribution from natural infection. TAK-003 was well tolerated.

No abstract