Study of Varying Injection Schedules of TDENV-PIV Vaccine With AS03B Adjuvant and Placebo in Healthy US Adults

Inclusion Criteria:

1. Subjects must be able to provide written informed consent.

2. Subjects must be healthy as established by medical history and clinical examination at
study entry

3. Subjects who the investigator believes can and will comply with the requirements of
the protocol (e.g., completion of the diary cards, return for follow-up visits, etc.)

4. Subjects at WRAIR CTC must be able to pass Department of Defense (DoD) base entry
requirements, including the possession of a valid government issued ID card.

5. Male or non-pregnant, non-breastfeeding female between 20 and 49 years of age
(inclusive) at the time of consent

6. Female subjects of non-childbearing potential (non-childbearing potential is defined
as having had one of the following: a tubal ligation at least 3 months prior to
enrollment, a hysterectomy, an ovariectomy, or is post-menopausal).

7. Female subjects of childbearing potential may be enrolled in the study, if all of the
following apply:

- Practiced adequate contraception (see Definition of Terms, section 5) for 30 days
prior to vaccination

- Has a negative urine pregnancy test on the day of vaccination

- Agrees to continue adequate contraception until two months after completion of
the vaccination series.

Exclusion Criteria:

1. Use of any investigational or non-registered product (drug or vaccine) other than the
study vaccines/placebo during the period starting 30 days preceding the first dose of
study vaccine/placebo and/or planned use during the study period

2. Chronic administration (defined as more than 14 days in total) of immunosuppressants
or other immune-modifying drugs during the period starting 90 days prior to the first
vaccine/placebo dose (for corticosteroids, this will mean prednisone >=5mg/day or
equivalent; inhaled, intranasal and topical steroids are allowed)

3. Planned administration or administration of a vaccine/product not planned in the study
protocol during the period starting 30 days prior to the first dose of vaccine/placebo
until 30 days after the last dose of study vaccine/placebo (routine influenza
vaccination will be allowed as long as it is not administered within 14 days of the
vaccine/placebo, and will not lead to study exclusion although it should be reported
to the PI)

4. History of dengue infection or dengue illness, or history of flavivirus vaccination
(e.g., yellow fever, tick-borne-encephalitis virus [TBEV], Japanese encephalitis, and
dengue)

5. Planned administration of any flavivirus vaccine for the entire study duration

6. Concurrently participating in another clinical study, at any time during the study
period, in which the subject has been or will be exposed to an investigational or a
non-investigational product (pharmaceutical product or device)

7. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on
medical history and physical examination (no laboratory testing required)

8. Family history of congenital or hereditary immunodeficiency

9. Autoimmune disease or history of autoimmune disease

10. History of any reaction or hypersensitivity likely to be exacerbated by any component
of the study vaccine/placebo or related to a study procedure

11. Major congenital defects or serious chronic illness

12. History of any neurological disorders or seizures

13. Diagnosed with excessive daytime sleepiness (unintended sleep episodes during the day
present almost daily for at least 1 month) or narcolepsy; or history of narcolepsy in
a subject's parent, sibling, or child

14. Acute disease and/or fever (≥37.5°C/99.5°F oral body temperature) at the time of
enrollment: note that a subject with a minor illness such as mild diarrhea, mild upper
respiratory infection, etc., without fever, may be enrolled at the discretion of the
investigator

15. Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal
functional abnormality, as determined by physical examination or laboratory screening
tests

16. Administration of immunoglobulins and/or any blood products during the period starting
90 days preceding the first dose of study vaccine/placebo or planned administration
during the study period

17. Recent history of chronic alcohol consumption (more than 2 drinks per day and/or drug
abuse (based on subject reported history)

18. Pregnant or breastfeeding female or female currently planning to become pregnant or
planning to discontinue adequate contraception

19. A planned move to a location that will prohibit participating in the trial until Study
End for the participant

20. Any other condition which, in the opinion of the investigator, prevents the subject
from participating in the study.

21. Subject seropositive for hepatitis B surface antigen (HBsAg), hepatitis C virus
antibodies (anti-HCV), or human immunodeficiency virus antibodies (anti-HIV)

22. Safety laboratory test results at screening that are deemed clinically significant or
more than Grade 1 deviation from normal