Safety and Immune Response to Two Doses of rDEN2/4delta30 Dengue Vaccine

Dengue fever, caused by dengue viruses, is a major health problem in the tropical and subtropical regions of the world. The purpose of this study is to test the safety of and immune response to a new dengue virus vaccine in healthy adults.

Dengue viruses, which cause dengue fever and dengue shock syndrome, are a major cause of morbidity and mortality in several of the world's tropical and subtropical regions. The rDEN2/4delta30(ME) vaccine is a live attenuated dengue virus vaccine that may be protective against dengue virus serotype 2 (DEN2). The purpose of this study is to evaluate the safety and immunogenicity of the rDEN2/4delta30(ME) vaccine in healthy adults.

This study will last approximately 5 to 7 months with 25 study visits. Participants will be randomly assigned into one of two cohorts. Participants in Cohort 1 will receive an injection of rDEN2/4delta30(ME) or placebo vaccine at Days 0 and 180. Participants in Cohort 2 will receive an injection of rDEN2/4delta30(ME) or placebo vaccine at Days 0 and 120. Participants will be asked to record their temperature in a diary for 16 days after each vaccination. At each study visit a physical examination, symptom history, and blood and urine collection will occur.

Eligibility Criteria:
Inclusion Criteria:

* Good general health as determined by means of the screening procedures.
* Available for the duration of the study (32 weeks for cohort 1 and 23 weeks for cohort 2)
* Willing to use effective methods of contraception

Exclusion Criteria:

* Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies
* Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator will affect the ability of the volunteer to understand and cooperate with the requirements of the study protocol
* Neutropenia as defined by an ANC ≤1500/mm3
* ALT level above the laboratory-defined upper limit of normal
* Serum creatinine level above the laboratory-defined upper limit of normal
* Any other condition that, in the opinion of the investigator, would jeopardize the safety or rights of a volunteer participating in the trial or would render the subject unable to comply with the protocol.
* Medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months
* History of a severe allergic reaction or anaphylaxis
* Severe asthma (emergency room visit or hospitalization within the last 6 months)
* Positive HIV-1 serology by screening and confirmatory assays
* Positive for hepatitis C virus (HCV) by screening and confirmatory assays
* Positive hepatitis B surface antigen (HBsAg) by enzyme-linked immunosorbent assay (ELISA)
* Known immunodeficiency syndrome
* Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days of starting this study
* Receipt of a live vaccine within the 4 weeks or a killed vaccine within the 2 weeks prior to entry into the study
* Has had spleen surgically removed
* Receipt of blood products within the 6 months prior to study entry
* History or serologic evidence of previous dengue virus infection or other flavivirus infection (e.g. yellow fever virus, St. Louis encephalitis, West Nile virus).
* Previous receipt of yellow fever or dengue vaccine (licensed or experimental)
* Persons who have received any investigational agent in the 30 days prior to study entry
* Persons who have definite plans to travel to a dengue endemic area during the study