Dataset Information

Bridging Efficacy of a Tetravalent Dengue Vaccine from Children/Adolescents to Adults in Highly Endemic Countries Based on Neutralizing Antibody Response.

ABSTRACT: The CYD-TDV vaccine is licensed in multiple endemic countries based on vaccine efficacy (VE) against symptomatic, virologically confirmed dengue demonstrated in two phase 3 trials (CYD14, 2- to 14-year-olds, Asia; CYD15, 9- to 16-year-olds, Latin America). 50% plaque reduction neutralization test (PRNT50) titers at baseline and month 13 (post-vaccination) were associated with VE and may enable bridging VE to adults. Two phase 2 trials of CYD-TDV measured baseline and month 13 PRNT50 titers: CYD22 (9- to 45-year-olds, Vietnam) and CYD47 (18- to 45-year-olds, India). 50% plaque reduction neutralization test distributions were compared between age cohorts, and four versions of an epidemiological bridging method were used to estimate VE against any serotype (dengue virus [DENV]-Any) and against each serotype over 25 months post first vaccination in a hypothetical CYD14 + CYD15 18- to 45-year-old cohort (bridging population 1) and in the actual CYD47 18- to 45-year-old cohort (bridging population 2). Baseline and month 13 geometric mean PRNT50 titers to each serotype were significantly greater in 18- to 45-year-olds than 9- to 16-year-olds for all comparisons. The four methods estimated VE against DENV-Any at 75.3-86.0% (95% CIs spanning 52.5-100%) for bridging population 1 and 68.4-77.5% (95% CIs spanning 42.3-88.5%) for bridging population 2. The vaccine efficacy against serotype 1, 2, 3, and 4 was estimated at 56.9-76.9%, 68.3-85.8%, 91.4-95.0%, and 93.2-100% (bridging population 1) and 44.5-66.9%, 53.2-69.2%, 79.8-92.0%, and 90.6-95.0% (bridging population 2), respectively; thus, CYD-TDV would likely confer improved efficacy in adults than 9- to 16-year-olds. Using the same methods, we predicted VE against hospitalized DENV-Any over 72 months of follow-up, with estimates 59.1-73.5% (95% CIs spanning 40.9-92.2%) for bridging population 1 and 50.9-65.9% (95% CIs spanning 38.1-82.1%) for bridging population 2.

SUBMITTER: Gilbert PB

PROVIDER: S-EPMC6609170 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Bridging Efficacy of a Tetravalent Dengue Vaccine from Children/Adolescents to Adults in Highly Endemic Countries Based on Neutralizing Antibody Response.

Gilbert Peter B PB Huang Ying Y Juraska Michal M Moodie Zoe Z Fong Youyi Y Luedtke Alexander A Zhuang Yingying Y Shao Jason J Carpp Lindsay N LN Jackson Nicholas N Chambonneau Laurent L Bouckenooghe Alain A Zambrano Betzana B Frago Carina C Pallardy Sophie S Noriega Fernando F

The American journal of tropical medicine and hygiene 20190701 1

The CYD-TDV vaccine is licensed in multiple endemic countries based on vaccine efficacy (VE) against symptomatic, virologically confirmed dengue demonstrated in two phase 3 trials (CYD14, 2- to 14-year-olds, Asia; CYD15, 9- to 16-year-olds, Latin America). 50% plaque reduction neutralization test (PRNT<sub>50</sub>) titers at baseline and month 13 (post-vaccination) were associated with VE and may enable bridging VE to adults. Two phase 2 trials of CYD-TDV measured baseline and month 13 PRNT<sub ...[more]

PMID: 31115304

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Project description:Three phase II randomized trials evaluated the safety/immunogenicity of two formulations of live-attenuated tetravalent dengue virus (TDEN) vaccine in dengue-endemic (Puerto Rico, Thailand) and non-endemic (US) regions (NCT00350337/NCT00370682/NCT00468858). We describe cell-mediated immune (CMI) responses; safety and humoral responses were reported previously. Participants received two doses of vaccine or control (placebo or the precursor live-attenuated TDEN vaccine) 6 months apart. Selected US participants received a booster 5-12 months post-dose 2. Evaluated subsets of the per-protocol cohorts included 75 primarily dengue virus (DENV)-unprimed US adults, 69 primarily flavivirus-primed Thai adults, and 100 DENV-primed or DENV-unprimed Puerto Rican adults/adolescents/children. T-cell responses were quantified using intracellular cytokine staining (ICS; DENV-infected cell-lysate or DENV-1/DENV-2 peptide-pool stimulation) or IFN-γ ELISPOT (DENV-2 peptide-pool stimulation). Memory B-cell responses were quantified using B-cell ELISPOT. Across populations and age strata, DENV serotype-specific CD4+ T-cell responses were slightly to moderately increased (medians ≤0.18% [ICS]), DENV-2-biased, and variable for both formulations. Responses in unprimed subjects were primarily detected post-dose 1. Response magnitudes in primed subjects were similar between doses. Multifunctional CD8+ T-cell responses were detected after peptide-pool stimulation. T-cell responses were mostly directed to DENV nonstructural proteins 3 and 5. Memory B-cell responses were tetravalent, of low-to-moderate magnitudes (medians ≤0.25%), and mainly observed post-dose 2 in unprimed subjects and post-dose 1 in primed subjects. A third dose did not boost CMI responses. In conclusion, both formulations of the live-attenuated TDEN vaccine candidate were poorly to moderately immunogenic with respect to B-cell and T-cell responses, irrespective of the priming status of the participants. Abbreviation ATP: according-to-protocol; ICS: Intracellular Cytokine Staining; NS3: Nonstructural protein 3; ELISPOT: Enzyme-Linked ImmunoSpot; JEV: Japanese encephalitis virus; PBMC: peripheral blood mononuclear cells.

Dataset Information

Bridging Efficacy of a Tetravalent Dengue Vaccine from Children/Adolescents to Adults in Highly Endemic Countries Based on Neutralizing Antibody Response.

Publications

Bridging Efficacy of a Tetravalent Dengue Vaccine from Children/Adolescents to Adults in Highly Endemic Countries Based on Neutralizing Antibody Response.

Similar Datasets

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