Long-term safety follow-up of children from a randomized-controlled phase Ⅱb proof-of-concept efficacy study of the live,attenuated,tetravalent dengue vaccine (CYD-TDV) in Thailand

Objective:To investigate the long-term safety of a tetravalent dengue vaccine(CYD-TDV)in children in a phase Ⅱ b follow-up study in Thailand.Methods:In the phase Ⅱb study,children aged 4-11 years were randomized(2:1)to receive three injections of CYD-TDV or serve as control at 6-month intervals,with 25 months’ active follow-up(active phase).This study was an additional four-year passive surveillance for hospitalized virologically-confirmed dengue(VCD;hospital phase).Cases of hospitalized VCD,severe hospitalized VCD,vaccine-related serious adverse events,and deaths were reported for the total population,with post-hoc analyses by enrollment age(<9 and≥9 years).Results:Of 3 997 participants receiving≥1 injection,80.1% were recruited to the hospital phase[2 131(CYD-TDV);1 072(control)].Eighty-five hospitalized VCD cases were reported in the CYD-TDV group and 46 in the control group during the four-year hospital phase[relative risk(RR):0.93,95% confidence interval(Cl):0.64-1.36].The RR over six years of follow-up was 0.77(95% CI:0.57-1.05).In those aged≥9 years,the cumulative RRs in the active phase,hospital phase,and entire six years were 0.28(95% CI:0.08-0.81),0.51(95% CI:0.25-1.05),and 0.42(95% CI:0.24-0.75),respectively.In the overall population,there were ten severe hospitalized VCD cases in the CYD-TDV group and five in the control group over six years(RR:1.00,95% CI:0.31-3.75).Conclusions:Over six years of follow-up,in children aged ≥9 years,CYD-TDV administration is associated with a reduced risk of hospitalized VCD.