TY - JOUR TI - Genetic epidemiology of dengue viruses in phase III trials of the CYD tetravalent dengue vaccine and implications for efficacy AU - Rabaa, Maia A AU - Girerd-Chambaz, Yves AU - Duong Thi Hue, Kien AU - Vu Tuan, Trung AU - Wills, Bridget AU - Bonaparte, Matthew AU - van der Vliet, Diane AU - Langevin, Edith AU - Cortes, Margarita AU - Zambrano, Betzana AU - Dunod, Corinne AU - Wartel-Tram, Anh AU - Jackson, Nicholas AU - Simmons, Cameron P A2 - Lipsitch, Marc VL - 6 PY - 2017 DA - 2017/09/05 SP - e24196 C1 - eLife 2017;6:e24196 DO - 10.7554/eLife.24196 UR - https://doi.org/10.7554/eLife.24196 AB - 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. KW - dengue virus KW - molecular epidemiology KW - dengue vaccine KW - virus evolution KW - genotype KW - vaccine JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -