This study is being conducted to evaluate the safety and immunogenicity and antibody persistence of the candidate dengue vaccine.

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