Zika virus (ZIKV) is an illness people can get from mosquitoes. The infection is generally mild with symptoms that include a fever, rash, red eyes, and joint pain, though most of those infected have no symptoms. Preventing ZIKV is important because if a pregnant person is infected with ZIKV, it can cause birth defects in their unborn child. The goals of this study are to find out if people who have already been infected with one type of ZIKV can get infected with ZIKV a second time, and to test the ability of the TV003 dengue vaccine to prevent people from getting infected with the ZIKV-SJRP challenge virus.
This study is an open label with 2 study arms. Arm 1 will evaluate the protective efficacy of TV003 against ZIKV challenge. Arm 1 will include infectivity controls who will receive PlasmaLyte (the TV003 diluent) and the treatment assignment will be blinded to reduce bias in the assessment of adverse events. The PlasmaLyte recipients will serve as infectivity controls to ensure the potency of the ZIKV challenge. The treatment assignment of the infectivity controls may be unblinded as early as 28 days after receipt of TV003/PlasmaLyte if they are needed for ZIKV-challenge of volunteers in Arm 2 and may be challenged earlier than the TV003 cohort. Arm 2 will evaluate the protective efficacy of previous ZIKV infection against subsequent ZIKV challenge. Both arms will be compared to historical controls who previously received ZIKV infection. Infectivity controls will not be included in the efficacy analysis. This study will include 16 flavivirus-naïve subjects for Arm 1. Twelve subjects will receive the live attenuated dengue vaccine candidate TV003 at Study Day 0 and 4 subjects will receive PlasmaLyte at Study Day 0. These subjects will be randomized in blocks of 4 (3 TV003:1 PlasmaLyte). At Study Day 180, Arm 1 subjects will receive the controlled human infection strain of ZIKV SJRP/2016-184 as a challenge virus. These subjects will include those volunteers who received TV003 and at least 1 of the infectivity controls who received PlasmaLyte. Subjects in Arm 1 will be followed for approximately 52 weeks (approximately 360 days) from the time of vaccination. Ten subjects who had a ZIKV infection, either from a previous ZIKV controlled human infection study where they had received either ZIKV SJRP/2016-184 or ZIKV Nicaragua/2016 or were excluded during screening for previous studies as having ZIKV infection, will be enrolled as a group in Arm 2. Subjects enrolled in Arm 2 will be challenged with the ZIKV SJRP/2016-184 challenge virus separately from TV003 recipients. At least 1 of the PlasmaLyte recipients enrolled in Arm 1 on Day 0 will be included in this group to receive ZIKV SJRP/2016-184 as an infectivity control. Arm 2 subjects will be followed after ZIKV challenge for approximately 26 weeks (approximately 180 days). Subjects will be screened for eligibility up to 60 days prior to vaccination on Study Day 0.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
26
0.5 ml of TV003 delivered via subcutaneous injection. TV003 contains 10\^3.3 plaque forming units (PFU)/mL of rDEN1Δ30, 10\^3.3 PFU/mL of rDEN2/4Δ30(ME), 10\^3.3 PFU/mL of rDEN3Δ30/31- 7164 and 10\^3.3 PFU/mL of rDEN4Δ30
0.5 mL of PlasmaLyte delivered via subcutaneous injection
0.5 ml of ZIKV-SJRP/2016-184 delivered via subcutaneous injection. ZIKV-SJRP/2016-184 contains a dose of 10\^2 plaque-forming units (PFU).
Center for Immunization Research, Johns Hopkins School of Public Health
Baltimore, Maryland, United States
RECRUITINGCenter for Immunization Research
Baltimore, Maryland, United States
RECRUITINGIncidence, magnitude, and duration of infectious ZIKV-SJRP/2016-184 recovered from serum following administration of ZIKV-SJRP/2016-184 in subjects who received TV003
Compared to historical controls
Time frame: Through 180 days post challenge
Incidence, magnitude, and duration of infectious ZIKV-SJRP/2016-184 recovered from serum following administration of ZIKV-SJRP/2016-184 in ZIKV-exposed subjects
Compared to historical controls
Time frame: Through 180 days post challenge
Proportion of subjects who received TV003 who develop clinical signs/symptoms of Zika infection
Compared to historical controls
Time frame: Through 180 days post challenge
Proportion of subjects who were previously infected with ZIKV who develop clinical signs/symptoms of Zika infection
Compared to historical controls
Time frame: Through 180 days post challenge
Frequency of immediate, systemic, and local adverse events (AEs) following vaccination with TV003
Time frame: Through 28 days post vaccination
Frequency of immediate, systemic, and local AEs following inoculation with ZIKV-SJRP/2016-184
Time frame: Through 28 days post challenge
Incidence, magnitude, and duration of ZIKV viremia induced by administering 10^2 PFU of ZIKV-SJRP/2016-184 in subjects who received TV003
Measured by quantitative polymerase chain reaction (PCR) induced, compared to historical controls.
Time frame: Through 6 months post challenge
Incidence, magnitude, and duration of ZIKV viremia induced by administering 10^2 PFU of ZIKV-SJRP/2016-184 in previously ZIKV-exposed subjects
Measured by quantitative PCR induced, compared to historical controls.
Time frame: Through 6 months post challenge
Number of TV003 vaccinees infected with DENV-1, DENV-2, DENV-3, and DENV-4 following administration of TV003
Infection is defined as recovery of vaccine virus from the blood or serum of a subject and/or by seropositivity to DENV measured by quantitative PCR
Time frame: Through 270 days post vaccination
Peak neutralizing antibody titer (NT) to DENV-1, DENV-2, DENV-3, and DENV-4
Measured by the NT50 at 28, 56, and 90 days after TV003 vaccination.
Time frame: Through 90 days post vaccination
Peak NT to ZIKV-SJRP/2016-184
Measured by NT50 at 0, 28, 56, and 90 days post-administration of ZIKV-SJRP
Time frame: Through 90 days post challenge
Number of volunteers who become infected following primary ZIKV-SJRP administration
Time frame: Through 16 days post challenge
Peak NT50 against ZIKV following TV003 vaccination correlates with protection against ZIKV infection
Time frame: Through 90 days post challenge
Evaluate boost in neutralizing antibody titers to DENV-1, DENV-2, DENV-3, and DENV-4 post-ZIKV challenge in subjects who received TV003
Peak NT50 achieved through 90 days post-ZIKV challenge in TV003 recipients. A boost in antibody titer is defined as a ≥ 4-fold rise through 90 days post challenge compared with the titer just prior to ZIKV challenge.
Time frame: Through 90 days post challenge
Evaluate boost in neutralizing antibody titers to ZIKV post challenge in subjects with previous ZIKV infection
Peak NT50 achieved through 90 days post-ZIKV challenge. A boost in antibody titer is defined as a ≥ 4-fold rise in peak ZIKV neutralizing antibody titer through 90 days post challenge compared with the ZIKV neutralizing antibody titer in serum collected just prior to ZIKV challenge.
Time frame: Through 90 days post-ZIKV challenge of previous ZIKV recipients
Quantity and duration of ZIKV in blood, cervico-vaginal secretions and semen
Measured by culture (infectious virus) and by reverse transcriptase - PCR in all participants receiving ZIKV-SJRP/2016-184
Time frame: Through 6 months post challenge
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