Estimated Efficacy of TAK-003 Against Asymptomatic Dengue Infection in Children/Adolescents Participating in the DEN-301 Trial in Asia Pacific and Latin America

Background TAK-003 has been shown to be well tolerated and effective against symptomatic dengue disease and hospitalization, irrespective of baseline serostatus. Most infections are asymptomatic/subclinical. This study assessed whether TAK-003 could protect against asymptomatic/subclinical infections by evaluating increased neutrlizing antibody titers (NAb) after natural infection. Methods DEN-301(NCT02747927) is a phase 3 trial among 4- to 16-year-old participants who received 2 doses of TAK-003/placebo 3 months apart. These exploratory analyses used NAb measured during the trial. As no well-accepted definition for asymptomatic infection exists, 3 algorithms were evaluated: (1) 4-fold increase in NAb, (2) 4-fold increase in NAb and a minimum titer of 40, and (3) 4-fold increase in NAb and a minimum titer of 4-fold lower-limit-of-quantification. Months 4-9, 9-15, and 15-27 after first vaccination were analyzed. Results NAb from 3765 participants were analyzed. From months 4-9, vaccine efficacy (VE) against asymptomatic infection was 51.1%(30.4 to 65.6), 36.1%(6.7–56.3), and 27.3%(−8.2 to 51.2) for algorithms 1, 2, and 3, respectively. VE in baseline seropositive participants per algorithms 1, 2, and 3 was 54.8%(28.8 to 71.3), 47.9%(16.8 to 67.4), and 44.3%(9.9 to 65.6), respectively, and in baseline seronegative participants was 44.4%(2.1 to 68.4), 4.6%(–85.1 to 50.8), and −29.3%(−172.1 to 38.6), respectively. VE against asymptomatic infection gradually decreased from months 4-9 to 9-15 and months 9-15 to 15-27. Conclusions The variability in VE algorithms indicates challenges in accurately assessing VE against asymptomatic infections. TAK-003 had a modest impact on asymptomatic dengue infections in the first months post-vaccination, mainly in baseline seropositive participants.