Evaluation of Two Zika Viruses for Use in Controlled Human Infection Models (CHIM)

Inclusion Criteria:

• Adult ZIKV and DENV-naïve male and non-pregnant females 18 - 40 years of age,inclusive.

• Good general health as determined by physical examination, laboratory screening, andreview of medical history.

• Available for the duration of the study, approximately 26 weeks post-inoculation.

• Must be able to complete the informed consent process and comprehension assessmentindependently and without assistance.

• Willingness to participate in the study as evidenced by signing the informed consentdocument.

• Willingness to reside in the inpatient unit for 9 days (or longer for safety ifnecessary) following receipt of ZIKV or placebo.

• Male subjects: Willingness to use barrier contraception during cervico-vaginal,anal, and oral intercourse through study day 90 (in accordance with CDC guidance).

• Female subjects: Willingness to use barrier contraception during cervico-vaginal,anal, and oral intercourse through study day 56 (in accordance with CDC guidance).

• Female subjects of childbearing potential must be willing to use effectivecontraception while at risk of Zika infection. CDC guidelines for the use ofeffective contraception of 8 weeks post-infection will be followed; time ofinfection is defined as inoculation with challenge virus. Reliable methods ofcontraception include: hormonal birth control* (implantable, hormonal patch,hormonal vaginal ring, oral contraception, Depo-Provera injection, etc.), surgicalsterilization (hysterectomy, tubal ligation, or tubal coil at least 3 months priorto inoculation), and intrauterine device. All female subjects will be consideredhaving child-bearing potential except for those with post-menopausal statusdocumented as at least 1 year since last menstrual period and females who have sexwith females (exclusively) and have no intention of conceiving a child during thestudy. Females who are not considered to be of childbearing potential will not berequired to use contraception other than barrier contraception for the purpose ofreducing potential transmission.

• Volunteers on hormonal birth control must not be on medications or other agentsthat decrease the effectiveness of hormonal birth control.

Exclusion Criteria:

• Currently pregnant, as determined by positive beta-human choriogonadotropin (Beta-hCG) test, breast-feeding or planning to become pregnant during the 6-monthduration of the study.

• Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic,rheumatologic, autoimmune, or renal disease by history, physical examination, and/orlaboratory studies.

• Behavioral, cognitive, or psychiatric disease that in the opinion of theinvestigator affects the ability of the subject to understand and cooperate with therequirements of the study protocol.

• Evidence of recent opiate use based on urine toxicology screen

• Screening laboratory values of Grade 1 or above for absolute neutrophil count (ANC),ALT, and serum creatinine, as defined in this protocol.

• Any other condition that in the opinion of the investigator would jeopardize thesafety or rights of a subject participating in the trial or would render the subjectunable to comply with the protocol.

• Any significant alcohol or drug abuse in the past 12 months which has causedmedical, occupational, or family problems, as indicated by subject history.

• History of a severe allergic reaction or anaphylaxis.

• Severe asthma (emergency room visit or hospitalization within the last 6 months).

• HIV infection, by screening and confirmatory assays.

• Hepatitis C virus (HCV) infection, by screening and confirmatory assays.

• Hepatitis B virus (HBV) infection, by hepatitis B surface antigen (HBsAg) screening.

• History of Guillain-Barré syndrome (GBS).

• History of seizure disease or peripheral neuropathy

• History of any neuroinflammatory disorder i.e. Bell's Palsy, transverse myelitis

• Any known immunodeficiency syndrome, including that caused by malignancy.

• Use of anticoagulant medications (use of antiplatelet medication such as aspirin ornon-steroidal anti-inflammatory medication is permitted and will not exclude asubject from enrollment).

• Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugswithin 28 days prior to or following inoculation. Immunosuppressive dose ofcorticosteroids is defined as ≥10 mg prednisone equivalent per day for ≥14 days.

• Receipt of a live vaccine within 21 days or a killed vaccine within the 14 daysprior to inoculation or anticipated receipt of any vaccine during the 21 daysfollowing inoculation.

• Asplenia.

• Receipt of blood products within the past 6 months, including transfusions orimmunoglobulin or anticipated receipt of any blood products or immunoglobulin duringthe 28 days following inoculation.

• History or serologic evidence of previous ZIKV infection or DENV infection.

• Previous receipt of a ZIKV or DENV vaccine (licensed or investigational).

• Anticipated receipt of any investigational agent in the 28 days before or afterinoculation.

• Subject has definite plans to travel to a ZIKV-endemic or dengue-endemic area duringthe study.

• Previous hypersensitivity to any study product component.

• Anaphylactic reaction to mosquito bites.

• Refusal to allow storage of specimens for future research.