Genetic epidemiology of dengue viruses in phase III trials of the CYD tetravalent dengue vaccine and implications for efficacy
2017
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
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.
Show more [+] Less [-]Bibliographic information
This bibliographic record has been provided by Directory of Open Access Journals