VRC 705: A Zika Virus DNA Vaccine in Healthy Adults and Adolescents

This is a multicenter, randomized study to evaluate safety, immunogenicity, and efficacy of a
3-dose vaccination regimen with the Zika virus wildtype (ZIKVwt) DNA vaccine,
VRC-ZKADNA090-00-VP or placebo (VRC-PBSPLA043-00-VP). The placebo is a sterile
phosphate-buffered saline (PBS). The hypotheses are that the ZIKVwt DNA vaccine will be safe
and will elicit a ZIKV-specific immune response.

Participants will receive study product intramuscularly (IM) in the limbs as specified by the
group assignment by PharmaJet needle-free device. In Part A, 90 participants will be
randomized to vaccine at a 1:1:1 ratio to receive a 4 mg or 8 mg dose of vaccine split
between 2 or 4 injections. In Part B, about 2400 participants will be randomized to vaccine
or placebo in a 1:1 ratio to receive a 4 mg dose of vaccine or 1 mL of placebo split between
2 injections.

Vaccine safety and tolerability will be assessed by monitoring of clinical and laboratory
parameters throughout the study. Solicited reactogenicity symptoms will be collected for 7
days after each product administration. The study schedule will include clinic visits with
safety and immunogenicity blood samples collected at particular time points.

The vaccine dose and administration plan for Part B was selected based on Part A and Phase 1
data. Vaccine efficacy will be evaluated in Part B by comparing incidence of ZIKV cases
between vaccine and placebo groups. During the study, when participants exhibit any possible
symptom of ZIKV infection, they will be evaluated by blood and urine ZIKV polymerase chain
reaction (PCR). Stored blood and urine samples will also be assessed retrospectively by ZIKV
PCR to identify possible asymptomatic cases. A Data and Safety Monitoring Board (DSMB) will
oversee the study.

Inclusion Criteria:

A subject must meet all of the following criteria:

Part A:

- 18 to 35 years of age

- Available for clinical follow-up through Study Week 32

- Accessible injection sites on each limb as follows: 1 injection site in the deltoid
muscle of each arm and 1 injection site in the vastus lateralis muscle of each
anterolateral thigh

Part B:

- 15 to 35 years of age

- Available for clinical follow-up through Study Week 96

- Accessible injection sites on the deltoid muscle of each arm. Injections sites on the
vastus lateralis muscle of the anterolateral thighs may be allowed with IND Sponsor
approval if an injection site on each deltoid muscle is not available.

Part A and B:

- Able to provide proof of identity to the satisfaction of the clinician completing the
enrollment process

- Able and willing to complete the informed consent/assent process

- Able and willing to complete the Assessment of Understanding and to verbalize
understanding of all questions answered incorrectly prior to signing consent/assent

- Willing to donate blood and urine to be stored and used for future research

- In good general health without clinically significant medical history

- Physical examination and laboratory results without clinically significant findings
within the 56 days prior to randomization

- Weight >30 kilograms (kg)

- Agree not to receive any licenses or investigational flavivirus vaccines through 4
weeks after last product administration

- Accessible injection sites on each limb as follows: 1 injections site in the deltoid
muscle of each arm and 1 injection site in the vastus lateralis muscle of each
anterolateral thigh.

Laboratory Criteria within 56 days prior to enrollment:

- Hemoglobin within site institutional normal limits

- Absolute neutrophil count (ANC) within site institutional normal limits

- Total lymphocyte count ≥800 cells/mm3

- Platelets = 125,000-510,000 cells/mm3

- Alanine aminotransferase (ALT) ≤1.5 x upper limit of normal (ULN) based on site
institutional normal range for respective age group

- Serum creatinine ≤1.2 x ULN based on site institutional normal range for respective
age group

- Negative result on an human immunodeficiency virus (HIV) test that meets local
standards for identification of HIV infection

Criteria applicable to women and adolescents of childbearing potential:

- Negative result on a human chorionic gonadotropin pregnancy test (urine or serum) on
day of randomization before receiving study product

- Agree to use effective means of birth control from at least 21 days before
randomization through 12 weeks after the last product administration

Criteria applicable to adolescents:

- Capability of the parent/guardian of the minor to understand and comply with planned
study procedures

- Capability of the minor and their parent/guardian to provide informed consent/assent

Exclusion Criteria:

Criteria applicable to women and adolescents of childbearing potential:

- Breast-feeding or planning to become pregnant while participating through 12 weeks
after the last product administration

Participant has received any of the following:

- More than 10 days of systemic immunosuppressive medications or cytotoxic medications
within the 4 weeks prior to randomization

- Any systemic immunosuppressive medications or cytotoxic medications within the 14 days
prior to randomization

- Blood products within 16 weeks prior to randomization

- Immunoglobulin within 8 weeks prior to randomization

- Investigational research agents within 4 weeks prior to randomization or planning to
receive investigational products while on the study

- Any vaccination within 2 weeks prior to randomization

- Any live attenuated vaccination within 4 weeks prior to randomization

- Current anti-tuberculosis (TB) prophylaxis or therapy

Participant has any of the following:

- Confirmed history of ZIKV infection (as reported by participant)

- Serious reactions to vaccines

- Chronic angioedema or chronic urticaria

- Asthma that is not well-controlled

- Diabetes mellitus (type I or II)

- Clinically significant autoimmune disease or immunodeficiency

- Hypertension that is not well-controlled

- Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or
platelet disorder requiring special precautions)

- Significant bruising or bleeding difficulties with IM injections or blood draws

- Malignancy that is active or history of a malignancy that is likely to recur during
the period of the study

- Seizure or treatment for a seizure disorder within the last 3 years

- Asplenia, functional asplenia or any condition resulting in the absence or removal of
the spleen

- History of Guillain-Barré Syndrome

- Psychiatric condition that may preclude compliance with the protocol; past or present
psychoses; or a history of suicide plan or attempt within 5 years prior to
randomization

- Any medical psychiatric, or social condition that, in the judgment of the
investigator, is a contraindication to protocol participation or impairs a
participant's ability to give informed consent