Long-term safety and immunogenicity of a tetravalent dengue vaccine candidate in children and adults: a randomized, placebo-controlled, phase 2 study.

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.