Efficacy and Safety of a Tetravalent Dengue Vaccine (TAK-003) in Children With Prior Japanese Encephalitis or Yellow Fever Vaccination
Chukiat Sirivichayakul, Shibadas Biswal, Xavier Sáez‐Llorens, Eduardo López‐Medina, Charissa Borja-Tabora, Lulu Bravo, Pope Kosalaraksa, Maria Theresa Alera, Humberto Reynales, Luis Rivera, Veerachai Watanaveeradej, Delia Yu, Félix Espinoza, Reynaldo Dietze, LakKumar Fernando, Pujitha Wickramasinghe, Edson Duarte Moreira, Asvini D. Fernando, Dulanie Gunasekera, Kleber Luz, Rivaldo Venâncio da Cunha, Ana Oliveira, Martina Rauscher, Huihao Fan, Astrid Borkowski, Ian Escudero, Suely Tuboi, Eric Lloyd, Vianney Tricou, Nicolas Folschweiller, Inge Lefevre, Luis Martinez Vargas, Derek Wallace, for the TIDES Study Group, Asvini D. Fernando, Charissa Borja-Tabora, Chukiat Sirivichayakul, Delia Yu, Dulanie Gunasekera, Eduardo López-Medina, Edith Johanna Rodriguez-Arenales, Edson Duarte Moreira, Félix Espinoza, Hector Velásquez, Humberto Reynales, Kleber Luz, José Jimeno, LakKumar Fernando, Lulu Bravo, Luis Martinez Vargas, Luis Rivera, Maria Theresa Alera, Onanong Manacharoen, Pío López, Pope Kosalaraksa, Pujitha Wickramasinghe, Reynaldo Dietze, Rivaldo Venâncio da Cunha, Veerachai Watanaveeradej, Xavier Sáez‐Llorens, Manja Brose, Shibadas Biswal, Yanee Hutagalung, Suely Tuboi
Abstract
BACKGROUND: We explored the impact of prior yellow fever (YF) or Japanese encephalitis (JE) vaccination on the efficacy of Takeda's dengue vaccine candidate, TAK-003. METHODS: Children 4-16 years of age were randomized 2:1 to receive TAK-003 or placebo and were under active febrile surveillance. Symptomatic dengue was confirmed by serotype-specific reverse-transcription polymerase chain reaction. YF and JE vaccination history was recorded. RESULTS: Of the 20 071 children who received TAK-003 or placebo, 21.1% had a YF and 23.9% had a JE vaccination history at randomization. Fifty-seven months after vaccination, vaccine efficacy (95% confidence interval) was 55.7% (39.7%-67.5%) in those with YF vaccination, 77.8% (70.8%-83.1%) for JE vaccination, and 53.5% (45.4%-60.4%) for no prior YF/JE vaccination. Regional differences in serotype distribution confound these results. The apparent higher vaccine efficacy in the JE vaccination subgroup could be largely explained by serotype-specific efficacy of TAK-003. Within 28 days of any vaccination, the proportions of participants with serious adverse events in the YF/JE prior vaccination population were comparable between the TAK-003 and placebo groups. CONCLUSIONS: The available data do not suggest a clinically relevant impact of prior JE or YF vaccination on TAK-003 performance. Overall, TAK-003 was well-tolerated and efficacious in different epidemiological settings. Clinical Trials Registration. NCT02747927.