Virological confirmation of suspected dengue in a Phase 2 Latin American vaccine trial: Implications for vaccine efficacy evaluation

Publication date: 2014 Source:Trials in Vaccinology, Volume 3 Author(s): Mark Boaz , Helene Janosczyk , Seema Garg , Stacy Yost , Stephen W. Hildreth , Gustavo Dayan , Linda Starr-Spires The CYD tetravalent dengue vaccine candidate is being evaluated for protective efficacy against symptomatic dengue in Phase 3 efficacy trials. The laboratory test algorithm to confirm dengue cases was evaluated prior to Phase 3 trials. During a Phase 2 trial in Latin America a dengue epidemic occurred in the study countries. A total of 72 suspected dengue cases were reported and assessed: virological confirmation comprised qRT-PCR methods and a commercial ELISA kit for NS1 protein (Bio-Rad). The qRT-PCR included a screening assay targeting a conserved dengue region of the 3′-UTR (dengue screen assay) followed by 4 individual serotype assays targeting the conserved dengue NS5 genomic region (WT dengue qRT-PCR assays). The NS1 and WT dengue qRT-PCR were endpoint assays for protocol virological confirmation (PVC). Of the 72 suspected cases, 14 were PVC. However, a unique pattern of dengue qRT-PCR results were observed in 5 suspected cases from Honduras: the dengue screen qRT-PCR assay was positive but WT dengue qRT-PCR and NS1 Ag ELISA were negative. To investigate these observations, additional molecular methods were applied: a SYBR® Green-based RT-PCR assay, sequencing assays directed at the genome regions covered by the WT dengue qRT-PCR, and a modified commercial dengue RT-PCR ...
Source: Trials in Vaccinology - Category: Infectious Diseases Source Type: research