Immunobridging Efficacy of a Tetravalent Dengue Vaccine Against Dengue and Against Hospitalized Dengue from Children/adolescents to Adults in Highly Endemic Countries.

Background: The recombinant tetravalent Live-attenuated dengue vaccine based on the YF 17D vaccine virus backbone (CYD-TDV) demonstrated vaccine efficacy (VE) against symptomatic, virologically confirmed dengue of any serotype from month 13 to month 25 (VCD-DENV-Any(M13 ->)(M25)) in the CYD14 (2-14-y-olds) and CYD15 (9-16-y-olds) phase 3 trials. Fifty percent plaque reduction neutralization test (PRNT50) titers are a potential surrogate for immunobridging VE to adults. Methods: Using PRNT50 calibration datasets, we applied immunobridging approaches using baseline and/or M13 PRNT50 titers to estimate VE against VCD-DENV-Any(M0 -> M25) and against hospitalized VCD (HVCD)-DENV-Any(M0 -> M72) in hypothetical 18-45-y-old and 46-50-y-old CYD14 and CYD15 cohorts. Results: Baseline and M13 geometric mean PRNT50 titers were greater in 18-45-y-olds and in 46-50-y-olds vs 9-16-y-olds for most comparisons. Estimated VE (95% CIs against VCD-DENV-Any(M0 -> M25) ranged from 75.3% to 90.9% (52.5% to 100%) for 18-45-y-olds and 74.8% to 92.0% (53.4% to 100%) for 46-50-y-olds. Estimated VE (95% CIs) against HVCD-DENV-Any(M0 -> M72) ranged from 58.8% to 78.1% (40.9 to 98.9%) for 18-45-y-olds and 57.2% to 78.4% (40.5 to 97.6%) for 46-50-y-olds. Corresponding predictions among baseline-seropositive individuals yielded comparable or higher VE estimates. Conclusions: VEM0 -> M25 against DENV-Any and VE against HVCD-DENV-Any(M0 -> M72) are both expected to be higher in 18-45 and 46-50-y-olds vs CYD14 and CYD15 9-16-y-olds.