This study will include 4 cohorts of 14 ZIKV and DENV-naïve female and male subjects, 18 - 40 years of age (total: up to 56 subjects). Within each cohort, 10 subjects will receive ZIKV and 4 subjects will receive a placebo on Study Day 0. Cohorts 1 and 2 (Dose = 10\^2 PFU) will be enrolled first and will enroll only women. Cohorts 3 and 4 (Dose = 10\^2 PFU) will enroll men.
This study is a placebo-controlled, double-blind study in normal healthy adult male and non-pregnant female subjects 18 - 40 years of age, inclusive, recruited from the metropolitan Baltimore/Washington, DC and Burlington, VT areas. The purpose of this study is to evaluate the clinical and virologic response to escalating doses of 2 different ZIKV strains administered subcutaneously in healthy, ZIKV and DENV-naïve, male and non-pregnant, female adult volunteers to identify the most suitable ZIKV strain and dose for use in a ZIKV CHIM. The ZIKV CHIM will then be used to evaluate the protective efficacy of candidate ZIKV vaccines prior to evaluation of these candidates in Phase 2 clinical trials. Both ZIKV strains will be studied at doses of 10\^2 PFU. Placebo recipients are included in the study as a control to better assess ZIKV-associated versus non-ZIKV-associated AEs.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
56
Zika Virus Strain (San Jose Rio Puerto)
Zika Virus Strain (Nicaragua)
Saline
Johns Hopkins University, Bloomberg School of Public Health
Baltimore, Maryland, United States
Number of Solicited Adverse Events
measured by count of solicited adverse events recorded following ZIKV administration
Time frame: Through 90 days post-inoculation
Severity of Adverse Events
count of solicited AEs by severity grade 1 - mild, event that is easily tolerated, may require 1 dose of medication. grade 2 - moderate, event that interferes with daily activity or requires more than 1 dose of medication. grade 3 - severe, event that prevents daily activity and requires medical intervention. grade 4 - life-threatening, an adverse event that is deemed by the study clinician, the medical monitor, or an outside clinician caring for the subject to be a life-threatening event. grade 5 - death, any adverse event that results in the death of the subject.
Time frame: Through 90 days post-inoculation
Number of Participants Infected by ZIKV
Infection defined as recovery of ZIKV by RT-PCR from blood and/or by seroconversion to ZIKV (50% plaque reduction neutralization titer \[PRNT50\]≥ 1:10)
Time frame: Through 90 days post-inoculation
Number of Participants With Zika Virus Recovered From Serum, Whole Blood, CVS, Semen, Urine, and Saliva
Count of participants with infectious virus recovered from serum, whole blood, cervicovaginal secretions (CVS), semen, urine, and saliva as measured by RT-PCR
Time frame: Through 90 days post-inoculation
Magnitude of ZIKV Recovered From Serum, Whole Blood, CVS, Semen, Urine, and Saliva
Mean peak titer of ZIKV recovered in serum, whole blood, cervicovaginal secretions (cvs), semen, urine, and saliva of participants by RT-PCR. Data are reported in Log10 Genome Equivalents (GE) per milliliter.
Time frame: Through 90 days post-inoculation
Duration of ZIKV in Serum, Whole Blood, CVS, Semen, Urine, and Saliva
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Mean number of days that ZIKV was recovered in serum, whole blood, cervicovaginal secretions (cvs), semen, urine, and saliva from participants with detectable zika as measured by RT-PCR
Time frame: Through 90 days post-inoculation
Frequency of AEs by Severity
Number of AEs by grade grade 1 - mild, event that is easily tolerated, may require 1 dose of medication. grade 2 - moderate, event that interferes with daily activity or requires more than 1 dose of medication. grade 3 - severe, event that prevents daily activity and requires medical intervention. grade 4 - life-threatening, an adverse event that is deemed by the study clinician, the medical monitor, or an outside clinician caring for the subject to be a life-threatening event. grade 5 - death, any adverse event that results in the death of the subject.
Time frame: Through 28 days post-inoculation
Number of Participants With Zika Virus Recovered From Serum, Whole Blood, CVS, Semen, Urine, and Saliva
determined by number of participants with infectious virus in serum, whole blood, cervicovaginal secretions (cvs), semen, urine, and saliva as measured by virus culture
Time frame: Through 90 days post-inoculation
Peak Virus Titer Recovered From Serum, Whole Blood, CVS, Semen, Urine, and Saliva
mean peak titer of ZIKV in participants with ZIKV recovered from serum, whole blood, cervicovaginal secretions (cvs), semen, urine, and saliva by virus culture. Data are reported in Log10 Genome Equivalents (GE) per milliliter.
Time frame: Through 90 days post-inoculation
Duration of ZIKV in Serum, Whole Blood, CVS, Semen, Urine, and Saliva
mean number of days that ZIKV was recovered in serum, whole blood, cervicovaginal secretions (cvs), semen, urine, and saliva from participants with detectable zika as measured by virus culture
Time frame: Through 90 days post-inoculation
Peak Neutralizing Antibody Response to ZIKV
evaluate the kinetics of the serum neutralizing antibody response following primary ZIKV infection.
Time frame: Through 90 days post-inoculation