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Dependency of Vaccine Efficacy on Preexposure and Age: A Closer Look at a Tetravalent Dengue Vaccine.

Abstract

Background

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

Methods

Combining the 2 phase 3 trials CYD14 and CYD15, we estimated the vaccine efficacy for each of the 4 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.

Results

Baseline seropositive subjects showed high efficacy for all serotypes: 70.2% (95% confidence interval [CI], 57.4%-80.1%) for dengue serotype 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% to 69.3%) for children ≤5 years old, 65.6% (95% CI, 40.3%-84.2%) for those 6-8 years old, 73.4% (95% CI, 62.6%-82.1%) for those 9-11 years old, and 80.6% (95% CI, 72.9%-87.3%) for those 12 years or older.

Conclusions

The CYD-TDV vaccine was highly efficacious for all dengue serotypes among children aged >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.

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  • Authors+Show Affiliations

    ,

    Department of Biostatistics and Emerging Pathogens Institute, University of Florida, Gainesville.

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    Department of Biostatistics and Emerging Pathogens Institute, University of Florida, Gainesville.

    ,

    Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle. Department of Biostatistics, University of Washington, Seattle.

    Department of Biostatistics and Emerging Pathogens Institute, University of Florida, Gainesville.

    Source

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    29020332