Analysis of hospitalized and severe dengue cases over the six-years of follow-up of the tetravalent dengue vaccine (CYD-TDV) efficacy trials in Asia and Latin America.

BACKGROUND CYD-TDV, a live, attenuated, tetravalent dengue vaccine, has been approved for the prevention of symptomatic dengue in previously dengue exposed individuals. This post-hoc analysis assessed hospitalized and severe virologically-confirmed dengue (VCD) over the complete 6-year follow-up of three CYD-TDV efficacy studies (CYD14, CYD15 and CYD23/CYD57). METHODS The main outcomes were hazard ratios (HRs) for hospitalized or severe VCD by baseline dengue serostatus, focusing on those who were seropositive, and by age at immunization (<9 years/≥9 years). Baseline dengue serostatus was measured or inferred using several methods. Hospitalized VCD cases were characterized in terms of clinical signs and symptoms and wild-type viremia level. Antibody persistence was assessed up to five years after the last injection. RESULTS In those aged ≥9 years and baseline seropositive, CYD-TDV protected against hospitalized and severe VCD over six years compared to placebo (HR [95% confidence interval] Multiple Imputation from Month 0 method, 0.19 [0.12-0.30] and 0.15 [0.06-0.39]; other methods were consistent). Vaccine protection was observed over the different study periods, being highest during the first 2 years. Evidence for a decreased risk of hospitalized and severe VCD was also observed in seropositive participants aged 6-8 years. Clinical signs and symptoms, and quantified dengue viremia from participants with hospitalized VCD were comparable between groups. CONCLUSIONS CYD-TDV demonstrated robust protection against hospitalized and severe VCD over the entire six-year follow-up in participants who were seropositive and ≥9 years old. Protection was also observed in seropositive 6-8 year olds.