title: Tetravalent Dengue Vaccine Reduces Symptomatic and Asymptomatic Dengue Virus Infections in Healthy Children and Adolescents Aged 2-16 Years in Asia and Latin America.
abstract: 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.
  
  
  
  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.
  
  
  
  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%).
  
  
  
  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.
authors.affiliation: Sanofi Pasteur, Lyon.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Olivera-Botello
authors.affiliation: Sanofi Pasteur, Lyon.
authors.forename: Laurent
authors.initials: L
authors.lastname: Coudeville
authors.affiliation: Sanofi, Chilly-Mazarin Cedex.
authors.forename: Karen
authors.initials: K
authors.lastname: Fanouillere
authors.affiliation: Sanofi Pasteur, Lyon.
authors.forename: Bruno
authors.initials: B
authors.lastname: Guy
authors.affiliation: Sanofi Pasteur, Marcy l'Etoile, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Chambonneau
authors.affiliation: Sanofi Pasteur, Swiftwater, Pennsylvania.
authors.forename: Fernando
authors.initials: F
authors.lastname: Noriega
authors.affiliation: Sanofi Pasteur, Marcy l'Etoile, France.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Jackson
mesh_terms: D000293:Adolescent; D000368:Aged; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D001208:Asia / Q000453:epidemiology; D058070:Asymptomatic Diseases / Q000453:epidemiology*; D002648:Child; D002675:Child, Preschool; D017326:Clinical Trials, Phase III as Topic; D003715:Dengue / Q000453:epidemiology* / Q000517:prevention & control*; D053059:Dengue Vaccines / Q000008:administration & dosage / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology*; D005260:Female; D006801:Humans; D007843:Latin America / Q000453:epidemiology; D008297:Male; D010919:Placebos / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; C000603176:CYD-TDV vaccine; D053059:Dengue Vaccines; D010919:Placebos
keywords: Asia; Latin America; adolescents; asymptomatic dengue virus infection; children; dengue vaccine; symptomatic dengue virus infection