Safety of and Immune Response to Two Different Dengue Virus Vaccines in Individuals Previously Immunized Against Dengue Virus

• Number, severity, and seriousness of vaccine-related adverse events observed through active and passive surveillance [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  
• Neutralizing antibody to all four dengue serotypes [ Time Frame: At Days 0, 28, and 42 ] [ Designated as safety issue: No ]
  

• Assess the frequency, quantity, and duration of viremia in each vaccine cohort studied [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• To determine if cellular targets of vaccine infection, including peripheral blood mononuclear cells and skin, are different after heterologous infection of a second dengue virus vaccine of a different serotype [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• Compare the safety and immunogenicity between each heterologous dengue vaccine virus cohort [ Time Frame: At study completion ] [ Designated as safety issue: No ]
  
• Evaluate the immunopathological mechanism of heterologous vaccine virus associated rash in those volunteers who are willing to undergo skin biopsy [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• Characterize the antibody response after heterolouous vaccine infection [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  

The World Health Organization estimates that dengue virus causes more than 50 million cases of dengue fever a year. Dengue virus infection is the leading cause of hospitalization and death in children of most tropical Asian countries. There are four different serotypes of dengue virus. Most cases of dengue hemorrhagic fever/dengue shock syndrome are caused by secondary infection with a dengue serotype different from the first serotype the individual was infected with. A vaccine that would be effective in preventing infection by multiple dengue serotypes is desirable. The purpose of this study is to determine the safety of and immune response to two different dengue virus vaccines in individuals who have been previously vaccinated against a different serotype.

This study will last at least 42 days. Participants will be recruited from a database of previous dengue vaccine recipients and will be stratified by the type of vaccine previously received. Participants assigned to Cohort 1 and Cohort 2 will have already been vaccinated with the rDEN4delta30 vaccine. Participants assigned to Cohort 3 will have already been vaccinated with the rDEN2/4delta30(ME) vaccine. Participants in Cohort 4 will have already been vaccinated with the rDEN1delta30 vaccine. Participants in Cohorts 1 and 3 will be randomly assigned to receive either the rDEN1delta30 vaccine or placebo. Participants in Cohorts 2 and 4 will be randomly assigned to receive either the rDEN2/4delta30(ME) vaccine or placebo.

Participants will receive their assigned vaccination on Day 0. Study visits will occur every other day until Day 16, and then at Days 21, 28, and 42. At each visit, blood collection, vital signs measurement, and a physical exam will occur. In addition, participants will be asked to monitor their temperature daily, 3 times a day, from Day 0 to Day 16. Patients will also be asked to enroll in an optional skin biopsy sub-study.