A Two-dose Primary Vaccination Study of a Tetravalent Dengue Virus Purified Inactivated Vaccine vs. Placebo in Healthy Adults

The study is designed to afford a safety and immunogenicity assessment of three Tetravalent
Dengue Virus-Purified Inactivated Vaccine(TDENV-PIV) vaccine candidates, each formulated with
a different adjuvant: either aluminum hydroxide, AS01E or AS03B (adjuvants used in Glaxo
Smith Kline (GSK) Biologicals' hepatitis B candidate vaccine, malaria candidate vaccine and
pandemic flu vaccine, respectively). Each vaccine candidate will contain 1 µg of purified
virus antigen per each of the four DENV types. Additionally, the study will evaluate an alum
adjuvanted TDENV-PIV vaccine candidate containing 4 µg of purified virus antigen per each of
the four DENV types. The control group will receive a saline placebo. All experimental
vaccinations will be administered according to a 2-dose schedule, 28 days apart.

Inclusion Criteria:

- 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.)

- A male or female between 18 and 39 years of age (inclusive) at the time of consent

- Written informed consent obtained from the subject

- Healthy subjects as established by medical history and clinical examination before
entering into the study

- Female subjects of non-childbearing potential (non-childbearing potential is defined
as having either a current tubal ligation at least three months prior to enrollment,
hysterectomy, ovariectomy, or is post-menopause). See Definition of Terms for adequate
contraception.

- Female subjects of childbearing potential may be enrolled in the study, if the subject
has:

- Practiced adequate contraception for 30 days prior to vaccination, and

- A negative urine pregnancy test on the day of vaccination, and

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

Exclusion Criteria:

- 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

- Chronic administration (defined as more than 14 days in total) of immunosuppressants
or other immune-modifying drugs during the period starting 180 days prior to the first
vaccine/placebo dose (for corticosteroids, this will mean prednisone ≥ 20 mg/day or
equivalent; inhaled and topical steroids are allowed)

- Planned administration or administration of a vaccine/product not foreseen by the
study protocol during the period starting 30 days prior to the first dose of
vaccine/placebo until after the visit at Day 56 (if influenza activity warrants
vaccination of healthy young adults, influenza vaccination will be encouraged and will
not lead to study exclusion)

- Planned administration of any flavivirus vaccine for the entire study duration

- 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).

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

- Family history of congenital or hereditary immunodeficiency

- History of, or current auto-immune disease

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

- Major congenital defects or serious chronic illness

- History of any neurological disorders or seizures

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

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

- 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

- History of chronic alcohol consumption and/or drug abuse

- Pregnant or lactating female or female planning to become pregnant or planning to
discontinue contraceptive precautions

- A planned move to a location that will prohibit participating in the trial until study
end for the participant

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

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

- Safety laboratory test results that are outside the acceptable values at screening.
The following values are not acceptable:

- >110% upper limit of normal (ULN) for alanine aminotransferase (ALT), aspartate
aminotransferase (AST), alkaline phosphatase, creatinine, serum urea nitrogen
(SUN) and bilirubin (total and direct)

- <100% lower limit of normal (LLN) or > 120% ULN for hemoglobin, hematocrit and
platelet count

- <75% LLN or >110% ULN for total white blood cell count (WBC) Note that all
screening laboratory results must be either within normal limits (WNL) or no more
than Grade l not clinically significant (NCS)

(LLN=lower limit of normal; ULN= upper limit of normal, WNL= within normal limits, NCS= not
clinically significant)