Immunogenicity and Safety of Tetravalent Dengue Vaccine Candidate (TDV) in Flavivirus-Naïve and Dengue-Immune Adults

The vaccine being tested in this study is Takeda's Tetravalent Dengue Vaccine Candidate
(TDV). TDV is being tested to protect people against dengue fever. This study will look at
the immunogenicity and safety of TDV in flavivirus-naïve and dengue-immune adults.

The study will enroll approximately 40 patients. Participants will be categorized into two
groups based on results from serological testing performed by the trial center outside the
scope of this trial (up to 35 days [5 weeks] prior to Day 1 [Month 0]):

Group 1: Flavivirus-Naïve Participants Group 2: Dengue-Immune Participants

All participants will receive subcutaneous injection of TDV on Day 1 (Month 0) and Day 90
(Month 3).

This trial will be conducted in the United States. The overall time to participate in this
study is 12 months. Participants will make multiple visits to the clinic, and 9 months after
last dose of study drug for a follow-up assessment.

Inclusion Criteria:

1. Who are in good health at the time of entry into the trial as determined by medical
history, physical examination (including vital signs) and clinical judgment of the
investigator.

2. Group 1 only: immunologically naïve to dengue, Zika, Yellow Fever (YF), Japanese
Encephalitis (JE), West Nile (WN) (based on negative results for detection of
anti-DENV, anti-Zika, anti-YF, anti-JE, anti-WN antibodies) as documented by
serological testing performed by the trial center outside the scope of this trial (up
to 35 days [5 weeks] prior to Day 1 [Month 0]).

3. Group 2 only: serology consistent with primary infection with either DENV-1 or DENV-3
(defined as detectable neutralizing antibodies against DENV-1 or DENV-3 only, or
titers for DENV-1 or DENV-3 ≥4-times higher than titers for the 2 other dengue
serotypes) as documented by serological testing performed by the trial center outside
the scope of this trial (up to 35 days [5 weeks] prior to Day 1 [Month 0]).

Exclusion Criteria:

1. Has clinically active significant infection (as assessed by the investigator) or body
temperature ≥38°C (100.4°F) within 3 days of the intended date of vaccination.

2. Has history of progressive or severe neurologic disorder, seizure disorder or
neuro-inflammatory disease (eg, Guillain-Barré syndrome).

3. Known or suspected impairment/alteration of immune function including:

1. Chronic use of oral steroids (equivalent to 20 mg/day prednisone ≥12 weeks and/or
≥2 mg/kg body weight/day prednisone ≥2 weeks) within 60 days prior to Day 1
(Month 0) (use of inhaled, intranasal, or topical corticosteroids is allowed).

2. Receipt of parenteral steroids (equivalent to 20 mg/day prednisone ≥12 weeks
and/or ≥2 mg/kg body weight/day prednisone ≥2 weeks) within 60 days prior to Day
1 (Month 0).

3. Administration of immunoglobulins and/or any blood products within 3 months prior
to Day 1 (Month 0) or planned administration during the trial.

4. Receipt of immunostimulants within 60 days prior to Day 1 (Month 0).

5. Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy
within 6 months prior to Day 1 (Month 0).

6. Known Human Immunodeficiency Virus (HIV) infection or HIV-related disease.

7. Hepatitis C virus infection.

8. Genetic immunodeficiency.

4. Has planned vaccination (during the trial conduct) against any non-dengue flavivirus
(eg, Zika, YF, JE, WN, tick-borne encephalitis, or Murray-Valley encephalitis).