Virologic, clinical, and immunological characteristics of a dengue virus 3 human challenge model

Dengue human infection models present an opportunity to explore a vaccine, antiviral, or immuno-compound’s potential for clinical benefit in a controlled setting. Herein, we report the outcome of a phase 1, open-label assessment of a DENV-3 challenge model. In this study, 9 participants received a subcutaneous inoculation with 0.5ml of a 1.4×103PFU/ml suspension of the DENV-3 strain CH53489. All subjects developed RNAemia within 7 days of inoculation, with peak titers ranging from 3.13×104to 7.02×108GE/ml. Symptoms and clinical lab abnormalities consistent with mild dengue infection were observed in all subjects. DENV-3 specific seroconversion was observed by 14 days after inoculation, along with DENV-3 specific memory T cell responses. RNAseq and serum cytokine analysis revealed the presence of an antiviral transcriptional and cytokine response to infection that overlapped with the period of viremia. The magnitude and frequency of clinical and immunologic endpoints correlated with an individual’s peak viral titer.