Dengue viruses can cause dengue fever and other serious health conditions, primarily affecting people living in tropical regions of the world. This study will evaluate the safety and immune responses to two formulations of a tetravalent dengue virus vaccine in healthy adults.
Dengue viruses cause dengue fever and the more severe condition, dengue hemorrhagic fever/shock syndrome. Dengue viruses are common in most tropical and subtropical regions of the world and infection with dengue viruses is the leading cause of hospitalization and death in children in many tropical Asian countries. For these reasons, the World Health Organization (WHO) has made the development of a dengue virus vaccine a top priority. This study will evaluate the safety and immunogenicity of two doses of a live, attenuated, tetravalent dengue virus vaccine called TetraVax-DV in healthy adults. Two different versions of the TetraVax-DV vaccine will be evaluated. This study will enroll healthy adults 18-50 years old. Participants will be randomly assigned to receive one of two admixtures of the TetraVax-DV vaccine or a placebo. At a baseline study visit, participants will undergo a medical history review, physical examination, blood collection, vital sign measurements, and a pregnancy test for females. Participants will then receive one injection of their assigned vaccine in the upper arm. After receiving the vaccine, participants will remain in the clinic for 30 minutes for observation and monitoring. At home, participants will monitor and record their temperature three times a day for 16 days. Additional study visits will occur at Days 3, 8, 10, 12, 14, 16, 21, 28, 56, 90, and 150 and will include a physical examination, assessment of symptoms, and blood collection. On Day 180, participants will receive a second injection of the same vaccine they received at the baseline study visit. Follow-up study visits will occur at Days 183, 188, 190, 192, 194, 196, 201, 208, 236, 270, and 360, and will include the same study procedures and monitoring that occurred after the first vaccination.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
112
One subcutaneous injection at Day 0 and Day 180 of a live attenuated recombinant TetraVax-DV vaccine, Admixture TV003 (10\^3 PFU of rDEN1Δ30, 10\^3 PFU of rDEN2/4Δ30(ME), 10\^3 PFU of rDEN3Δ30/31-7164, and 10\^3 PFU of rDEN4Δ30)
One subcutaneous injection at Day 0 and Day 180 of a live attenuated recombinant TetraVax-DV vaccine, Admixture TV005 (10\^3 PFU of rDEN1Δ30, 10\^4 PFU of rDEN2/4Δ30(ME), 10\^3 PFU of rDEN3Δ30/31-7164, and 10\^3 PFU of rDEN4Δ30)
One subcutaneous injection at Day 0 and Day 180 of placebo
Center for Immunization Research, Johns Hopkins School of Public Health
Baltimore, Maryland, United States
Fletcher Allen Health Care (FAHC), General Clinical Research Center (GCRC)
Burlington, Vermont, United States
University of Vermont Vaccine Testing Center
Burlington, Vermont, United States
Safety of two TetraVax-DV admixtures, as assessed by the frequency of vaccine-related adverse events (AEs), graded by severity
Time frame: Measured through Day 360
Immunogenicity of two TetraVax-DV admixtures, as assessed by neutralizing antibody titers to DEN1, DEN2, DEN3, and DEN4
Monovalent, bivalent, trivalent, and tetravalent seropositivity and seroconversion rates will be determined at 28, 56, and 90 days after each vaccination.
Time frame: Measured through Day 180 after each vaccination
Seropositivity in those vaccinees who remained seronegative to one or more DENV serotypes following the first vaccination and who recieved a second dose of vaccine given at Day 180
Time frame: Measured through Day 360
Frequency of viremia following vaccination
Time frame: Measured through Day 360
Number of vaccinees infected with DEN1, DEN2, DEN3, and DEN4
Infection is defined as recovery of vaccine virus from the blood or serum of a participant and/or by seropositivity to DEN virus (PRNT50 greater than or equal to 1:10).
Time frame: Measured through Day 360
Duration of the neutralizing antibody response 26 weeks after each vaccination
Time frame: Measured 26 weeks after each vaccination
Ability of a second dose of vaccine to boost serum neutralizing antibody titers by Day 270
Boost will be defined as a greater than or equal to 4-fold rise in serum neutralizing antibody titer by Day 270 compared with Day 180.
Time frame: Measured at Day 270
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Evaluate the phenotype of peripheral blood mononuclear cells at primary infection with the TetraVax-DV vaccine
Time frame: Measured through Day 360
Evaluate the cellular immune response to primary infection with the TetraVax-DV vaccine
Time frame: Measured through Day 360
Evaluate the innate immune response to primary infection with the TetraVax-DV vaccine
Time frame: Measured through Day 360
Evaluate B and T cell memory responses following primary and secondary infections with TetraVax-DV vaccine
Time frame: Measured through Day 360
Quantity of viremia following vaccination
Time frame: Measured through Day 360
Duration of viremia following vaccination
Time frame: Measured through Day 360