Immunogenicity and Safety of Tetravalent Dengue Vaccine (TDV) Administered With a Yellow Fever Vaccine in Adults

Seroprotection was defined as reciprocal anti-YF neutralizing antibody titer ≥10. Immunological naivety to YF and DENV was defined as Baseline reciprocal neutralizing antibody titers \<10 for YF and for the 4 dengue serotypes. The 95% CI was calculated using exact Clopper-Pearson method.

Time frame: Day 30

Population: Yellow Fever Per-Protocol Set (YF PPS) included all participants YF and DENV-naïve at Baseline who received \>=1 dose of trial vaccine, with data available for Baseline and Day 30, and who had no major protocol violations. Overall number analyzed are participants with data available for analyses at given time point within pre-specified visit window.

Geometric mean titers of YF neutralizing antibodies was measured by plaque reduction neutralization test.

Time frame: 1-month post-third vaccination (Day 210)

Population: PPS included all participants YF and DENV-naïve at Baseline who received \>=1 dose of trial vaccine, with data available for Baseline and \>=1 post-Baseline immunogenicity measurement, and who had no major protocol violations. Overall number analyzed: participants with data available for analyses at given time point within pre-specified visit window.

Geometric mean titers of YF neutralizing antibodies was measured by plaque reduction neutralization test.

Time frame: 1-month post-first vaccination (Day 30)

Population: YF PPS included all participants YF and DENV-naïve at Baseline who received \>=1 dose of trial vaccine, with data available for Baseline and Day 30, and who had no major protocol violations. Overall number analyzed are participants with data available for analyses at given time point within pre-specified visit window.

GMTs of neutralizing antibodies was measured by microneutralization test 50% \[MNT50\] for each of the 4 dengue serotypes. The 4 DENV serotypes are DENV-1, DENV-2, DENV-3 and DENV-4.

Time frame: Pre-second and -third vaccination (Days 90 and 180, respectively); and 1 month post -first, second, and third vaccination (Days 30, 120, and 210, respectively)

Population: Per-Protocol Set (PPS) included all participants YF and DENV-naïve at Baseline who received \>=1 dose of trial vaccine, with data available for Baseline and \>=1 post-Baseline immunogenicity measurement, and who had no major protocol violations.Number analyzed are participants with data available at given time point within pre-specified visit window.

Seropositivity rate was defined as the percentage of seropositive participants as derived from the titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10. Seropositivity for each dengue serotype were analyzed and was summarized as: DENV-1, DENV-2, DENV-3, and DENV-4.

Time frame: Pre-second and -third vaccination (Days 90 and 180, respectively); and 1-month post -first, -second, and -third vaccination (Days 30, 120, and 210, respectively)

Population: PPS included all participants YF and DENV-naïve at Baseline who received \>=1 dose of trial vaccine, with data available for Baseline and \>=1 post-Baseline immunogenicity measurement, and who had no major protocol violations. Number analyzed are participants with data available at given time point within pre-specified visit window.

Seropositivity rate was defined as the percentage of seropositive participants, as derived from the titers of dengue-neutralizing antibodies. Seropositivity was defined as a reciprocal neutralizing titer ≥10. Seropositivity for multiple dengue serotypes were summarized in the following categories: at least bivalent, at least trivalent and tetravalent.

Time frame: Pre-second and -third vaccination (Days 90 and 180, respectively); and 1-month post -first, second, and -third vaccination (Days 30, 120, and 210, respectively)

Population: PPS included all participants YF and DENV-naïve at Baseline who received \>=1 dose of trial vaccine, with data available for Baseline and \>=1 post-Baseline immunogenicity measurement, and who had no major protocol violations. Number analyzed are participants with data available at given time point within pre-specified visit window.

An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a trial vaccine; it does not necessarily have to have a causal relationship with trial vaccine administration.

Time frame: Within 28 days (day of vaccination + 27 days) after each vaccination

Population: Safety Set included all randomized participants who received at least 1 dose of the trial vaccines. Number analyzed is the number of participants with data available for analyses at the given timepoint.

MAAEs are defined as AEs leading to an unscheduled visit to or by a healthcare professional including visits to an emergency department, but not fulfilling seriousness criteria.

Time frame: From first vaccination (Day 1) through end of study (Day 360)

Population: Safety Set included all randomized participants who received at least 1 dose of the trial vaccines.

An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, leads to a congenital anomaly/birth defect in the offspring of a participant, is an important medical event that may require intervention to prevent any of the above mentioned criteria and/or may expose the subject to danger, even though the event is not immediately life threatening or fatal or does not result in hospitalization.

Time frame: From first vaccination (Day 1) through end of study (Day 360)

Population: Safety Set included all randomized participants who received at least 1 dose of the trial vaccines.

An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a trial vaccine; it does not necessarily have to have a causal relationship with trial vaccine administration. Solicited local injection site AEs recorded from participant's-diary. Severity grade at injection site for pain: Grade 0 (No Pain), 1 (did not interfere with daily activity), 2 (interference with daily activity with or without treatment) and 3 (prevents daily activity with or without treatment). For erythema: grade 0 (\<25 mm), 1 (\>25-≤50 mm), 2 (\>50-≤100 mm) and 3 (\>100 mm). For swelling: grade 0 (\<25 mm), 1 (\>25-≤50 mm), 2 (\>50-≤100 mm) and 3 (\>100 mm). Percentages were rounded off for each category. For the first vaccination (Vac.) YF is given in Arm 1 (A1) and TDV is given in Arm 2 (A2). A1 = YF for Group 1, Placebo for Group 2, and YF for Group 3; A2 = Placebo for Group 1, TDV for Group 2, and TDV for Group 3.

Time frame: Within 7 Days of each Vaccination (day of vaccination + 6 days)

Population: Safety Set included all randomized participants who received at least 1 dose of the trial vaccines. Number analyzed are participants with data available for the category. Only categories with at least one participant are reported.

Solicited systemic AEs (fever, headache, asthenia, malaise, and myalgia) recorded from participant's-diary. Severity grades for headache are grade 0 (none), 1 (mild: no interference with daily activity), 2 (moderate: interference with daily activity with or without treatment) and 3 (severe: prevents normal activity with or without treatment). Severity grades for asthenia, malaise and myalgia is grade 0 (none), 1 (mild: no interference with daily activity), 2 (moderate: interference with daily activity), 3 (severe: prevents daily activity). Fever is defined as greater than or equal to 38º C or 100.4º C. Fever was excluded from the overall count as no severity grading was applied for it. Percentages were rounded off for each category.

Time frame: Within 14 Days of each Vaccination (day of vaccination + 13 days)

Population: Safety Set included all randomized participants who received at least 1 dose of the trial vaccines. Number analyzed are participants with data available for the category. Only categories with at least one participant are reported.

Seroprotection was defined as reciprocal anti-YF neutralizing antibody titer ≥10.

Time frame: 1-month post third vaccination (Day 210)

Population: PPS included all participants YF and DENV-naïve at Baseline who received \>=1 dose of trial vaccine, with data available for Baseline and \>=1 post-Baseline immunogenicity measurement, and who had no major protocol violations. Overall number analyzed: participants with data available for analyses at given time point within pre-specified visit window.