Immunobridging efficacy of a tetravalent dengue vaccine against dengue and against hospitalized dengue from children/adolescents to adults in highly endemic countries. (28th December 2020) - Huang, Ying
Abstract: 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-AnyM13→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-AnyM0→M25 and against hospitalized VCD (HVCD)-DENV-AnyM0→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-AnyM0→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-AnyM0→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: VE M0→M25 against DENV-Any and VE against HVCD-DENV-AnyM0→M72 are both expected to be higher in 18–45 and 46–50-y-olds vs CYD14 and CYD15 9–16-y-olds.