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

Safety and Immunogenicity of a 2-Dose Regimen of rDEN2/4Δ30 Dengue Vaccine With Boosting at 4 Versus 6 Months

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.

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