Dengue viruses can cause dengue fever and other more serious illnesses. The purpose of this study is to evaluate the safety and immune response to a dengue virus vaccine.
Dengue viruses can cause dengue fever and the more severe disease, dengue hemorrhagic fever/shock syndrome (DHF/DSS). Infection with dengue viruses is the leading cause of hospitalization and death in children in at least 8 tropical Asian countries. There are 4 types of dengue virus (DENV-1, DENV-2, DENV-3, and DENV-4), each of which can cause dengue illness ranging from a mild illness to life-threatening disease. This study will evaluate the experimental rDEN2Δ30-7169 vaccine for the prevention of illness due to DENV-2. The purpose of this study is to evaluate the safety and immunogenicity of this vaccine in healthy adults with no history of previous flavivirus infection. At study entry, participants will be randomly assigned to receive either the dengue virus vaccine or placebo. They will remain in the clinic for 30 minutes after receiving the injection for monitoring. Study visits will occur at Days 2, 4, 6, 8, 10, 12, 14, 16, 21, 28, 56, and 180. All study visits will include a blood collection, and most study visits will include a physical examination. Female participants will have a pregnancy test at select visits. Participants will record their temperature at least 3 times a day for the first 16 days; study researchers will review these readings during the study visits.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
14
Administered at a dose of 10\^3 plaque-forming units (PFU); delivered by subcutaneous injection in the deltoid region of the upper arm
Delivered by subcutaneous injection in the deltoid region of the upper arm
John Hopkins Bloomberg School of Public Health - Center for Immunization Research (CIR)
Baltimore, Maryland, United States
Safety of rDEN2Δ30-7169 vaccine as assessed by the frequency of vaccine-related adverse events (AEs)
AEs are classified by both severity and seriousness, through active and passive surveillance.
Time frame: Measured through participants' last study visit at Day 180
Frequency, quantity, and duration of viremia following vaccination
Subjects will have samples assayed for vaccine virus on Study Days 0, 2, 4, 6, 8, 10, 12, 14, and 16. Serum will be serially diluted and the titer of vaccine virus determined.
Time frame: Measured through participants' last study visit at Day 180
Immune response of the vaccine at 4 and 8 weeks post-vaccination
Seropositivity to DENV-2 is defined as PRNT50 ≥ 1:10. Seroconversion is defined as a ≥ 4-fold rise in PRNT50 to wt DENV-2 Tonga/74 by Study Day 56.
Time frame: Measured at 4 and 8 weeks post-vaccination
Titer of virus vaccine
The peak titer, day of onset, and duration of viremia will be calculated for each subject within the vaccinated group.
Time frame: Measured through participants' last study visit at Day 180
Number of vaccinees who seroconvert to DENV-2 by study Day 56
Seroconversion will be defined as a ≥ 4-fold rise in PRNT50 to wt DENV-2 Tonga/74 by Study Day 56.
Time frame: Measured through Day 56
Number of vaccinees infected with rDEN2Δ30-7169 vaccine
Infection is defined as recovery of vaccine virus from the blood or serum of a subject and/or by seroconversion to DENV-2 defined as a ≥ 4-fold rise in DENV-2 neutralizing antibody titers by Study Day 56 when compared with Study Day 0.
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Time frame: Measured through participants' last study visit at Day 180
Comparison of infectivity rates, safety, and immunogenicity of a single dose of rDEN2Δ30 vaccine with the reported infectivity and safety of rDEN2/4Δ30 from previous clinical trials
Time frame: Measured through participants' last study visit at Day 180
Durability of neutralizing antibody by measuring serum neutralizing antibody to DENV-2 out to 180 days after vaccination
Time frame: Measured through participants' last study visit at Day 180