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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 publication

DOI

10.7554/eLife.24196

Type

Journal article

Journal

Elife

Publication Date

05/09/2017

Volume

6

Keywords

dengue vaccine, dengue virus, epidemiology, genotype, global health, molecular epidemiology, vaccine, virus, virus evolution, Amino Acid Sequence, Amino Acids, Antibodies, Monoclonal, Base Sequence, Clinical Trials, Phase III as Topic, Dengue Vaccines, Dengue Virus, Epitopes, Genotype, Geography, Humans, Molecular Epidemiology, Phylogeny, Serogroup, Treatment Outcome, Viral Envelope Proteins