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

Maia A. Rabaa, Yves Girerd-Chambaz, Kien Duong Thi Hue, Trung Vu Tuan, Bridget Wills, Matthew Bonaparte, Diane Van Der Vliet, Edith Langevin, Margarita Cortes, Betzana Zambrano, Corinne Dunod, Anh Wartel-Tram, Nicholas Jackson, Cameron P. Simmons

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Abstract

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.

Original languageEnglish
Article numbere24196
Number of pages22
JournaleLife
Volume6
DOIs
Publication statusPublished - 5 Sep 2017
Externally publishedYes

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