Abstract
A safe and efficacious vaccine for dengue is seen as the best rationale for decreasing the burden of morbidity and mortality associated with dengue infection. Identification of acute phase soluble factors as biomarkers of successful vaccination would has ten the development of a dengue vaccine. The Walter Reed Army Institute Research (WRAIR) is exploring the potential of a Prime-Boost vaccine strategy using purified inactivated virus (PIV) and live attenuated virus (LAV) tetravalent dengue vaccine candidates. A phase 1 clinical trial was performed testing different dosing schedules, PIV followed by LAV or vice versa at 0–1 or 0–6 months. Plasma samples were collected pre-vaccination and at multiple time points immediately post-vaccination to assess the kinetics of the acute phase soluble factor response to vaccination. We tested the plasma samples using Luminex-based magnetic bead kits measuring 59 different chemokines and cytokines. Our results reveal that different cytokine profiles were induced in subjects depending on the vaccine modality and whether it was given as the prime or boost dose. LAV appeared to be most immunogenic, particularly when received as a booster dose after PIV priming. Production of cytokines, including sCD30, APRIL, sTNF-R2, and IL-1RA, occurred in the majority of subjects tested approximately 10–14days post-vaccination. This study supports other data from this trial demonstrating that the type of vaccine and the order in which it is received impacts immunogenicity. Correlations of soluble factor responses with traditional adaptive immune responses, such as neutralizing antibody and IFN-γ ELISpot assays, will be presented.