Neutralizing antibody correlates analysis of tetravalent dengue vaccine efficacy trials in Asia and Latin America

Z Moodie, M Juraska, Y Huang… - The Journal of …, 2018 - academic.oup.com
Z Moodie, M Juraska, Y Huang, Y Zhuang, Y Fong, LN Carpp, SG Self, L Chambonneau…
The Journal of infectious diseases, 2018academic.oup.com
Background In the CYD14 and CYD15 Phase 3 trials of the CYD-TDV dengue vaccine,
estimated vaccine efficacy (VE) against symptomatic, virologically confirmed dengue (VCD)
occurring between months 13 and 25 was 56.5% and 60.8%, respectively. Methods
Neutralizing antibody titers to the 4 dengue serotypes in the CYD-TDV vaccine insert were
measured at month 13 in a randomly sampled immunogenicity subcohort and in all VCD
cases through month 25 (2848 vaccine, 1574 placebo) and studied for their association with …
Background
In the CYD14 and CYD15 Phase 3 trials of the CYD-TDV dengue vaccine, estimated vaccine efficacy (VE) against symptomatic, virologically confirmed dengue (VCD) occurring between months 13 and 25 was 56.5% and 60.8%, respectively.
Methods
Neutralizing antibody titers to the 4 dengue serotypes in the CYD-TDV vaccine insert were measured at month 13 in a randomly sampled immunogenicity subcohort and in all VCD cases through month 25 (2848 vaccine, 1574 placebo) and studied for their association with VCD and with the level of VE to prevent VCD.
Results
For each trial and serotype, vaccinees with higher month 13 titer to the serotype had significantly lower risk of VCD with that serotype (hazard ratios, 0.19–0.43 per 10-fold increase). Moreover, for each trial, vaccinees with higher month 13 average titer to the 4 serotypes had significantly higher VE against VCD of any serotype (P < .001).
Conclusions
Neutralizing antibody titers postdose 3 correlate with CYD-TDV VE to prevent dengue. High titers associate with high VE for all serotypes, baseline serostatus groups, age groups, and both trials. However, lowest titers do not fully correspond to zero VE, indicating that other factors influence VE.
Oxford University Press