부산대학교 도서관

Background: Yellow fever (YF) vaccination is often mandatory for travelers to YF-endemic areas. The areas with risk of YF partially overlap with those of dengue, for which there is currently no recommended vaccine available for dengue-naïve individuals. This phase 3 study assessed the immunogenicity and safety of concomitant and sequential administration of YF (YF-17D) and tetravalent dengue (TAK-003) vaccines in healthy adults aged 18–60 years living in areas of the US non-endemic for either virus. Methods: Participants were randomized 1:1:1 to receive the following vaccinations at Months 0, 3, and 6, respectively: YF-17D+placebo, TAK-003, and TAK-003 (Group 1); TAK-003+placebo, TAK-003, and YF-17D (Group 2); or YF-17D+TAK-003, TAK-003, and placebo (Group 3). The primary objective was to demonstrate non-inferiority (upper bound of 95% confidence interval [UB95%CI] of difference <5%) of YF seroprotection rate one month following concomitant administration of YF-17D and TAK-003 (Group 3) compared with YF-17D plus placebo (Group 1). The secondary objectives included demonstration of non-inferiority of YF and dengue geometric mean titers (GMTs) (UB95%CI for GMT ratio <2.0), and safety. Results: 900 adults were randomized. YF seroprotection rates one month post-YF-17D (Month 1) were 99.5% and 99.1% in Group 1 and 3, respectively, and non-inferiority was demonstrated (UB95%CI = 2.69% i.e. <5%). Non-inferiority was also demonstrated for GMTs against YF one month post-YF-17D, and against DENV-2, -3, and -4 (UB95%CI <2), but not DENV-1 (UB95%CI: 2.22), one month post-second TAK-003 vaccination. Adverse event rates following TAK-003 were consistent with previous results, and no important safety risks were identified. Conclusions: In this study, YF-17D vaccine and TAK-003 were immunogenic and well tolerated when sequentially or concomitantly administered. The non-inferiority of immune responses to YF-17D and TAK-003 was demonstrated for concomitant administration of the 2 vaccines compared to separate vaccination, except against DENV-1 but with GMTs similar to those observed in other TAK-003 trials. Trial registration: ClinicalTrials.gov identified: NCT03342898. Author summary: Dengue and yellow fever are diseases endemic to tropical regions, often occurring in the same areas. There are highly effective vaccines against yellow fever, but there remains an unmet need for a dengue vaccine which can be used in people regardless of previous dengue infection. As multiple vaccines are often given together, particularly in travel medicine, we investigated the immunogenicity and safety of co-administration and sequential administration of a yellow fever vaccine and a tetravalent dengue vaccine (TAK-003) in adults living in areas of the US non-endemic for either disease. Most participants did not have pre-existing antibodies to either disease. We found that there was no reduction in immune response to the yellow fever vaccine when given at the same time as the dengue vaccine. There was also no reduction in response to dengue serotypes 2, 3, and 4, but this could not be established for the response to serotype 1. When sequentially administered, temporary increases were observed in yellow fever seroprotection rates after receipt of TAK-003, and in dengue seropositivity rates after receipt of the yellow fever vaccine, but these differences among groups were no longer seen by the end of the study. Both vaccines were well tolerated with acceptable safety profiles. [ABSTRACT FROM AUTHOR]