The Effects of Japanese Encephalitis Vaccine and Accelerated Dosing Scheduling on the Immunogenicity of the Chimeric Yellow Fever Derived Tetravalent Dengue Vaccine (CYD-TDV): A Phase II, Randomized, Open-label, Single Center Trial in Adults Aged 18 to 45 years in the United States.

Dengue is a global health problem requiring an effective, safe dengue vaccine. We report the results of a phase II, randomized, open-label, single center trial in adults aged 18 to 45 years in the United States designed to explore the effects of the Chimeric Yellow Fever-Derived Tetravalent Dengue Vaccine (CYD-TDV, Dengvaxia) when administered on its designated schedule (months 0, 6 and 12) or on an accelerated dosing schedule (months 0, 2 and 6) and/or given prior to, or concomitantly with, a vaccine against Japanese Encephalitis (JE). Based on DENV serotype-specific neutralizing antibody (NAb), the accelerated dosing schedule was comparable to the 0, 6, and 12-month schedule. Giving JE vaccine concurrently with CYD-TDV did not result in an increase in overall NAb titers. Immunophenotyping of peripheral blood mononuclear cells (PBMCs) revealed an increase in activated CD8+ T cells after CYD-TDV vaccination, a phenomenon which was greatest for the JE vaccine primed. We conclude that an accelerated dosing schedule of CYD-TDV results in essentially equivalent dengue serotype-specific NAb titers as the currently used schedule and there may be an early benefit in antibody titers and activated CD8+ T cells by the administration of the JE vaccine prior to CYD-TDV vaccination. (Trial Registered at ClinicalTrials.gov: NCT01943825).