Efficacy of a Dengue Vaccine Candidate (TAK-003) in Healthy Children and Adolescents 2 Years after Vaccination
Eduardo López‐Medina, Shibadas Biswal, Xavier Sáez‐Llorens, Charissa Borja-Tabora, Lulu Bravo, Chukiat Sirivichayakul, Luis Martinez Vargas, Maria Theresa Alera, Hector Velásquez, Humberto Reynales, Luis Rivera, Veerachai Watanaveeradej, Edith Johana Rodriguez-Arenales, Delia Yu, Félix Espinoza, Reynaldo Dietze, Lak Kumar Fernando, Pujitha Wickramasinghe, Edson Duarte Moreira, Asvini D. Fernando, Dulanie Gunasekera, Kléber Giovanni Luz, Rivaldo Venâncio da Cunha, Vianney Tricou, Martina Rauscher, Mengya Liu, Inge Lefevre, Derek Wallace, Pope Kosalaraksa, Astrid Borkowski
Abstract
BACKGROUND: Takeda's dengue vaccine is under evaluation in an ongoing phase 3 efficacy study; we present a 2-year update. METHODS: Children (20 099, 4-16 years old) were randomized to receive 2 doses of TAK-003 or placebo 3 months apart and are under surveillance to detect dengue by serotype-specific RT-PCR. RESULTS: Cumulative efficacy against dengue approximately 27 months since first dose was 72.7% (95% confidence interval [CI], 67.1%-77.3%), including 67.0% (95% CI, 53.6%-76.5%) in dengue-naive and 89.2% (95% CI, 82.4%-93.3%) against hospitalized dengue. In the second year, decline in efficacy was observed (56.2%; 95% CI, 42.3%-66.8%) with the largest decline in 4-5 year olds (24.5%; 95% CI, -34.2% to 57.5%); efficacy was 60.6% (95% CI, 43.8%-72.4%) in 6-11 year and 71.2% (95% CI, 41.0%-85.9%) in 12-16 year age groups. As TAK-003 efficacy varies by serotype, changes in serotype dominance partially contributed to efficacy differences in year-by-year analysis. No related serious adverse events occurred during the second year. CONCLUSIONS: TAK-003 demonstrated continued benefit independent of baseline serostatus in reducing dengue with some decline in efficacy during the second year. Three-year data will be important to see if efficacy stabilizes or declines further.Clinical Trials Registration. NCT02747927.Takeda's tetravalent dengue vaccine (TAK-003) continued to demonstrate benefit in reducing dengue independent of baseline serostatus up to 2 years after completing vaccination with some decline in efficacy during the second year in 4-16 year olds in dengue-endemic countries.