• Frequency of vaccine-related adverse events, as classified by both intensity and severity through active and passive surveillance [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  
• Immunogenicity, determined by anti-WN/DEN4 neutralizing antibody titer [ Time Frame: At study entry, Days 28 and 42 after first vaccination, and Days 180, 208, and 222 after second vaccination ] [ Designated as safety issue: No ]
  

• Assess the frequency, quantity, and duration of viremia after each dose of vaccine by dose cohort (10^4 or 10^5 PFU) [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• Determine the number of vaccinees infected with WN/DEN4delta30 in each dose cohort (10^4 or 10^5 PFU) [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• Compare the infectivity rates, safety, and immunogenicity between dose 1 and dose 2 within a cohort and between cohorts [ Time Frame: At study completion ] [ Designated as safety issue: No ]
  

WN is widely distributed in Africa and Europe, where it is usually associated with mild illness. In the United States, WN is considered a public health threat because severe illness caused by WN infection has caused paralysis, coma, and death, especially in the elderly. This study will evaluate the safety and immunogenicity of a live attenuated chimeric virus, WN/DEN4delta30, which is derived from the DEN4 dengue virus and wild-type WN serotypes.

This study will last at least 32 weeks. Participants in Cohort 1 will be randomly assigned to receive 1X10^4 plaque-forming units (PFU) WN/DEN4delta30 or placebo at study entry and Day 180. Cohort 2 will be randomly assigned to receive a higher dose of WN/DEN4delta30, 10^5 PFU, or placebo at study entry and Day 180. Immediately after receiving their injections, participants will be observed for 30 minutes for immediate adverse reactions.

After each vaccination, participants will be asked to monitor their temperatures three times every day for 16 days. Study visits will occur every other day after each vaccination until Day 16, followed by three additional visits at selected days through Day 180 post-vaccination. Blood collection, medical history, vital signs measurement, and a targeted physical exam will occur at all visits. Participants will also be required to keep temperature diaries until Day 16 after vaccination. Female participants will have a urine pregnancy test performed within 60 days of study entry, and on Days 28, 42, 150, 180, 208, and 222. Pregnancy prevention counseling will occur at selected visits.

Inclusion Criteria:

• Good general health
• Available for the duration of the trial
• Willing to use acceptable forms of contraception for the duration of the study

Exclusion Criteria:

• Clinically significant neurologic, heart, lung, liver, rheumatologic, autoimmune, or kidney disease
• Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, affects the ability of the volunteer to understand and cooperate with the study
• Neutropenia (abnormally low neutrophil count)
• Alcohol or drug abuse within 12 months prior to study entry
• Elevated levels of alanine aminotransferase (ALT) and serum creatinine
• History of severe allergic reaction or anaphylaxis
• Severe asthma
• HIV-1 infected
• Hepatitis C virus infected
• Hepatitis B surface antigen positive
• Known immunodeficiency syndrome
• Use of corticosteroids or immunosuppressive drugs within 30 days of study entry. Participants who have used topical or nasal corticosteroids are not excluded.
• Live vaccine within 4 weeks prior to study entry
• Killed vaccine within 2 weeks prior to study entry
• Surgical removal of spleen
• Blood products within 6 months prior to study entry
• History of dengue virus infection or other flavivirus infection (e.g., yellow fever virus, St. Louis encephalitis, West Nile virus)
• Previously received a licensed or experimental yellow fever or dengue vaccine
• Investigational agent within 30 days of study entry
• Other condition that, in the opinion of the investigator, would affect the participant's participation in the study
• Pregnancy or breastfeeding