Genetic epidemiology of dengue viruses in phae III trials of the CYD tetravalent dengue vaccine and implications for efficacy

This study defined the genetic epidemiology of dengue viruses (DENV) in two pivotal phase III trials of the tetravalent dengue vaccine, CYD-TDV, and thereby enabled virus genotype-specific estimates of vaccine efficacy (VE). Envelope gene sequences (n = 661) from 11 DENV genotypes in 10 endemic coun...

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Auteur principal: Simmons, Cameron
Format: Journal Article
Langue:anglais
Publié: 2018
Accès en ligne:https://demo7.dspace.org/handle/123456789/180
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author Simmons, Cameron
author_browse Simmons, Cameron
author_facet Simmons, Cameron
author_sort Simmons, Cameron
collection DSpace
description This study defined the genetic epidemiology of dengue viruses (DENV) in two pivotal phase III trials of the tetravalent dengue vaccine, CYD-TDV, and thereby enabled virus genotype-specific estimates of vaccine efficacy (VE). Envelope gene sequences (n = 661) from 11 DENV genotypes in 10 endemic countries provided a contemporaneous global snapshot of DENV population genetics and revealed high amino acid identity between the E genes of vaccine strains and wild-type viruses from trial participants, including at epitope sites targeted by virus neutralising human monoclonal antibodies. Post-hoc analysis of all CYD14/15 trial participants revealed a statistically significant genotype-level VE association within DENV-4, where efficacy was lowest against genotype I. In subgroup analysis of trial participants age 9-16 years, VE estimates appeared more balanced within each serotype, suggesting that genotype-level heterogeneity may be limited in older children. Post-licensure surveillance is needed to monitor vaccine performance against the backdrop of DENV sequence diversity and evolution.
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spelling oai:localhost:123456789-1802021-04-07T16:30:08Z Genetic epidemiology of dengue viruses in phae III trials of the CYD tetravalent dengue vaccine and implications for efficacy Simmons, Cameron This study defined the genetic epidemiology of dengue viruses (DENV) in two pivotal phase III trials of the tetravalent dengue vaccine, CYD-TDV, and thereby enabled virus genotype-specific estimates of vaccine efficacy (VE). Envelope gene sequences (n = 661) from 11 DENV genotypes in 10 endemic countries provided a contemporaneous global snapshot of DENV population genetics and revealed high amino acid identity between the E genes of vaccine strains and wild-type viruses from trial participants, including at epitope sites targeted by virus neutralising human monoclonal antibodies. Post-hoc analysis of all CYD14/15 trial participants revealed a statistically significant genotype-level VE association within DENV-4, where efficacy was lowest against genotype I. In subgroup analysis of trial participants age 9-16 years, VE estimates appeared more balanced within each serotype, suggesting that genotype-level heterogeneity may be limited in older children. Post-licensure surveillance is needed to monitor vaccine performance against the backdrop of DENV sequence diversity and evolution. 2018-09-14T11:15:03Z 2017-10-11T01:12:07Z 2018-09-14T11:15:03Z 2017-08-03 2017-08-03 2017-08-03 2017-08-03 2017-08-03 2017-08-03 2017-08-03 2017-08-03 2017-08-03 2017-08-03 2017-08-03 2017-08-03 2017-09-05 Journal Article https://demo7.dspace.org/handle/123456789/180 English
spellingShingle Simmons, Cameron
Genetic epidemiology of dengue viruses in phae III trials of the CYD tetravalent dengue vaccine and implications for efficacy
title Genetic epidemiology of dengue viruses in phae III trials of the CYD tetravalent dengue vaccine and implications for efficacy
title_full Genetic epidemiology of dengue viruses in phae III trials of the CYD tetravalent dengue vaccine and implications for efficacy
title_fullStr Genetic epidemiology of dengue viruses in phae III trials of the CYD tetravalent dengue vaccine and implications for efficacy
title_full_unstemmed Genetic epidemiology of dengue viruses in phae III trials of the CYD tetravalent dengue vaccine and implications for efficacy
title_short Genetic epidemiology of dengue viruses in phae III trials of the CYD tetravalent dengue vaccine and implications for efficacy
title_sort genetic epidemiology of dengue viruses in phae iii trials of the cyd tetravalent dengue vaccine and implications for efficacy
url https://demo7.dspace.org/handle/123456789/180
work_keys_str_mv AT simmonscameron geneticepidemiologyofdenguevirusesinphaeiiitrialsofthecydtetravalentdenguevaccineandimplicationsforefficacy