Tetravalent Dengue Vaccine Reduces Symptomatic and Asymptomatic Dengue Virus Infections in Healthy Children and Adolescents Aged 2-16 Years in Asia and Latin America

Gustavo Olivera-Botello, Laurent Coudeville, Karen Fanouillere, Bruno Guy, Laurent Chambonneau, Fernando Noriega, Nicholas Jackson, José Luis Arredondo-García, Alain Bouckenooghe, Maria Rosario Capeding, Tawee Chotpitayasunondh, Mary Noreen Chua, Margarita Cortés Supelano, Carmen Deseda, Reynaldo Dietze, Carina Frago, Sri Rezeki S. Hadinegoro, Chan Quang Luong, Hussain Imam Hj Muhammad Ismail, Revathy NallusamyPunnee Pitisuttithum, Humberto Reynales, Doris Maribel Rivera-Medina, Kusnandi Rusmil, Usa Thisyakorn, Ngoc Huu Tran, T. Anh Wartel, Dewa Nyoman Wirawan, In Kyu Yoon, Betzana Zambrano

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)


Background.Asymptomatic dengue virus-infected individuals are thought to play a major role in dengue virus transmission. The efficacy of the recently approved quadrivalent CYD-TDV dengue vaccine against asymptomatic dengue virus infection has not been previously assessed. Methods.We pooled data for 3 736 individuals who received either CYD-TDV or placebo at 0, 6, and 12 months in the immunogenicity subsets of 2 phase 3 trials (clinical trials registration NCT01373281 and NCT01374516). We defined a seroconversion algorithm (ie, a ≥4-fold increase in the neutralizing antibody titer and a titer of ≥40 from month 13 to month 25) as a surrogate marker of asymptomatic infection in the vaccine and placebo groups. Results.The algorithm detected seroconversion in 94% of individuals with a diagnosis of virologically confirmed dengue between months 13 and 25, validating its discriminatory power. Among those without virologically confirmed dengue (n = 3 669), 219 of 2 485 in the vaccine group and 157 of 1 184 in the placebo group seroconverted between months 13 and 25, giving a vaccine efficacy of 33.5% (95% confidence interval [CI], 17.9%-46.1%) against asymptomatic infection. Vaccine efficacy was marginally higher in subjects aged 9-16 years (38.6%; 95% CI, 22.1%-51.5%). The annual incidence of asymptomatic dengue virus infection in this age group was 14.8%, which was 4.4 times higher than the incidence for symptomatic dengue (3.4%). Conclusions.The observed vaccine efficacy against asymptomatic dengue virus infections is expected to translate into reduced dengue virus transmission if sufficient individuals are vaccinated in dengue-endemic areas.

Original languageEnglish
Pages (from-to)994-1000
Number of pages7
JournalJournal of Infectious Diseases
Issue number7
Publication statusPublished - 1 Oct 2016


  • Asia
  • Latin America
  • adolescents
  • asymptomatic dengue virus infection
  • children
  • dengue vaccine
  • symptomatic dengue virus infection


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