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Background The immune profile of dengue-experienced individuals is a determinant of dengue reinfection severity risk. Individuals with a single prior dengue infection (monotypic) are at highest risk for severe disease, while individuals with ≥ 2 prior dengue infections (multitypic) are at lower risk. The tetravalent dengue vaccine (CYD-TDV) has shown efficacy in the prevention of dengue in individuals with prior dengue infection. We estimated efficacy in individuals with monotypic or multitypic immune profiles. Methods Participants enrolled in the immunogenicity subsets of 2 randomized placebo-controlled phase 3 studies (CYD14, NCT01373281; CYD15, NCT01374516) were classified as either monotypic or multitypic, based on measured baseline dengue plaque reduction neutralization test. Vaccine efficacy (VE) against symptomatic virologically confirmed dengue (VCD) was assessed over 25 months and against VCD hospitalization over 6 years. Results Of 3927 participants in the immunogenicity subsets, 496 and 257 in the CYD-TDV and placebo groups, respectively, were classified as monotypic immune, and 1227 and 612, respectively, as multitypic immune. VE against symptomatic VCD was 77.4% (95% CI, 56.4%–88.2%) for monotypic and 89.2% (95% CI, 71.5%–95.9%) for multitypic profiles, with corresponding absolute risk reductions (ARRs) of 4.48% (95% CI, 2.32%–6.65%) for monotypics and 1.67% (95% CI,.89%–2.46%) for multitypics. VE against hospitalized VCD was 75.3% (95% CI, 42.7%–90.2%) in monotypics and 81.2% (95% CI, 21.7%–96.8%) in multitypics, with ARRs of 0.95% (95% CI,.37%–1.53%) for monotypics and 0.18% (95% CI,.02%–.34%) for multitypics. Conclusions CYD-TDV benefits individuals with monotypic and multitypic immune profiles. Larger public health benefit is expected to derive from the protection of individuals with a monotypic immune profile. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]