Dependency of Vaccine Efficacy on Pre-Exposure and Age: A Closer Look at a Tetravalent Dengue Vaccine

Yang Yang, Ya Meng, M. Elizabeth Halloran, Ira M. Longini, Jr.

Clinical Infectious Diseases

August 24, 2017



A recombinant, live-attenuated, tetravalent dengue vaccine (CYD-TDV) was licensed for children of 9 years old or older in a few countries, but the dependence of vaccine efficacy on baseline immunity status and age groups has not been fully characterized.


Combining the two phase III trials, CYD14 and CYD15, we estimated the vaccine efficacy for each of the four serotypes of dengue virus (DENV), as well as all serotypes combined, simultaneously stratified by baseline immunity status and age group, while accounting for uncertainty in the baseline immunity status of subjects.


Baseline seropositive subjects showed high efficacy for all serotypes, 70.2% (95% confidence interval [CI]: 57.4, 80.1) for dengue 1 (DENV-1), 67.9% (95% CI: 49.9, 82.0) for DENV-2, 77.5% (95% CI: 64.3, 90.2) for DENV-3, 89.9% (95% CI: 79.8, 99.9) for DENV-4, and 75.4% (95% CI: 68.3, 81.6) overall. In contrast, baseline seronegative subjects showed moderate efficacy against DENV-4, 51.2% [95% CI: 20.0, 72.8] but no significant efficacy against other serotypes. Among seropositive children, the overall efficacy tended to increase with age, 35.9% (95% CI: -7.6, 69.3) for children ≤5 years old, 65.6% (95% CI: 40.3, 84.2) for 6 – 8 years old, 73.4% (95% CI: 62.6, 82.1) for 9 – 11 years old, and 80.6% (95% CI: 72.9, 87.3) for 12 years or older.


The CYD-TDV vaccine was highly efficacious for all dengue serotypes among children older than 5 years who have acquired baseline immunity from previous exposure. Increasing vaccine efficacy with age was not fully explained by increasing prevalence of baseline immunity with age.