Safety of and Immune Response to a Dengue Virus Vaccine (rDEN3delta30/31‐7164) in Healthy Adults

• Determine the safety of a single dose of the rDEN3Δ30/31‐7164 vaccine, as assessed by the frequency, severity, and seriousness of vaccine related adverse events (AEs). [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  
• Determine the immunogenicity of a single dose of the rDEN3delta30/31‐7164 vaccine, as assessed by neutralizing antibody titers to DEN3 at 4 weeks and 6 weeks after vaccination [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  

• Assess the frequency, quantity, and duration of viremia after a single dose of vaccine [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• Determine the number of vaccinees infected with rDEN3delta30/31‐7164. Infection is defined as recovery of vaccine virus from the blood or serum of a volunteer and/or by seroconversion to DEN3 (a ≥4‐fold rise in DEN3 neutralizing antibody titers). [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  
• Compare the infectivity rates, safety, and immunogenicity of a single dose of rDEN3delta30/31‐7164 vaccine between the dose level groups. [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• Determine the durability of antibody response 26 weeks after vaccination [ Time Frame: At 26 weeks ] [ Designated as safety issue: No ]
  
• Obtain an estimate for the Human Infectious Dose‐50% (HID50) if dose dependent infectivity is observed [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• Evaluate the phenotype of peripheral blood mononuclear cells at primary infection with the rDEN3delta30/31‐7164 vaccine. [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• Evaluate the cellular and humoral immune response to primary infection with the rDEN3delta30/31‐7164 vaccine [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  

More than 2 billion people living in tropical and subtropical regions of the world are at risk of dengue virus infection. Dengue viruses cause dengue fever, as well as the more severe dengue hemorrhagic fever/shock syndrome, and dengue virus infection is the leading cause of hospitalization and death in children in several tropical Asian countries. This study will evaluate the safety and immunogenicity of a live, attenuated dengue virus called rDEN3delta30/31‐7164.

This study will consist of two groups, with Group 1 enrolling first. Group 1 participants will be randomly assigned to receive either 10^3 PFU of rDEN3delta30/31-7164 or placebo subcutaneously in their deltoid. Participants will be monitored at the clinic for 30 minutes after receiving the immunization to monitor for adverse effects. After that, participants will be asked to return to the clinic approximately every other day for the next 16 days, and then on Day 21, 28, 42, and 180. At each visit participants will have physical and clinical exams, vital signs, measures, blood drawn, and will be asked about any adverse events they may have experience. Female participants will be given a pregnancy test. In addition, participants will be asked to measure their temperature 3 times a day and record it in a temperature diary for the first 16 days after immunization.

If less than 90% of the participants in Group 1 seroconvert to DEN3 then Group 2A will be enrolled. Group 2A will follow the same procedures as Group 1, but will receive a 10^5 PFU dose of rDEN3delta30/31-7164.

If more than 90% of the participants in Group 1 seroconvert to DEN3 then Group 2B will be enrolled. Group 2A will follow the same procedures as Group 1, but will receive a 10^1 PFU dose of rDEN3delta30/31-7164.