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A recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV) has been assessed in two phase 3 randomized efficacy trials involving more than 31,000 children between the ages of 2 and 14 years in the Asian–Pacific region (CYD14 trial) and between the ages of 9 and 16 years in Latin America (CYD15 trial).1,2 The vaccine was administered in three doses: at baseline, at 6 months, and at 12 months. Vaccine efficacy against virologically confirmed dengue and safety were assessed during a 25-month efficacy surveillance phase (i.e., until 13 months after the third dose was administered). Reactogenicity and immunogenicity were also assessed in a subgroup of participants.1,2 Vaccination significantly reduced the incidence of virologically confirmed dengue and showed acceptable safety and reactogenicity profiles, findings that were consistent with earlier results.
In the ongoing longer-term follow-up (from year 3 to year 6) to assess safety, we are monitoring the incidence of hospitalization for dengue as a surrogate end point for disease severity in order to evaluate a potential predisposition in vaccinated persons to increased severity of disease.3 In addition, we invited the 4002 children between the ages of 4 and 11 years from a single-center phase 2b trial (CYD23) in Thailand that had a study design similar to that of the CYD14 and CYD15 trials to participate in a separate study (CYD57) of 4 years of follow-up in which we are assessing safety in a similar way to the way it is being assessed in the two phase 3 trials.4 Here we report the interim analyses of data from the long-term safety phase and integrated analyses of data from the efficacy surveillance phase to provide a global view of the clinical profile of the CYD-TDV dengue vaccine.
Methods
Trial Procedures and Oversight
Interim Long-Term Safety Analyses
The long-term safety analyses are based on data collected during year 3 of two phase 3 trials in five Asian–Pacific countries (CYD14) and five Latin American countries (CYD15) and during years 3 and 4 of the CYD23 extension study (CYD57) in Thailand (Figure 1). The participants were originally randomly assigned in a 2:1 ratio to the vaccine group or the control group, stratified according to age, with a subgroup of participants assigned to a study...