The Effects Of Japanese Encephalitis Vaccine And Accelerated Dosing Scheduling On The Immunogenicity Of The Chimeric Yellow Fever Derived Tetravalent Dengue Vaccine: A Phase Ii, Randomized, Open-Label, Single-Center Trial In Adults Aged 18 To 45 Years In The United States

Background. Dengue is a global health problem requiring an effective, safe dengue vaccine.Methods. 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 before, or concomitantly with, a vaccine against Japanese encephalitis (JE).Results. Based on dengue virus 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 revealed an increase in activated CD8(+) T cells after CYD-TDV vaccination, a phenomenon that was greatest for the JE vaccine primed.Conclusions. 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 before CYD-TDV vaccination.