Genetic epidemiology of dengue viruses in phase III trials of the CYD tetravalent dengue vaccine and implications for efficacy.
Maia A RabaaYves Girerd-ChambazKien Duong Thi HueTrung Vu TuanBridget WillsMatthew BonaparteDiane van der VlietEdith LangevinMargarita CortesBetzana ZambranoCorinne DunodAnh Wartel-TramNicholas JacksonCameron P SimmonsPublished in: eLife (2017)
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.
Keyphrases
- phase iii
- dengue virus
- zika virus
- open label
- aedes aegypti
- clinical trial
- phase ii
- genome wide
- double blind
- placebo controlled
- amino acid
- single cell
- wild type
- study protocol
- risk factors
- public health
- copy number
- young adults
- endothelial cells
- physical activity
- randomized controlled trial
- gene expression
- middle aged
- multidrug resistant
- cancer therapy
- transcription factor
- klebsiella pneumoniae