Vaccine to Prevent West Nile Virus Disease
Vaccine to Prevent West Nile Virus Disease
This study will test the safety of an experimental vaccine intended to prevent West Nile
 virus (WNV) infection and determine if it causes side effects. WNV symptoms may vary from
 fever and headache, to a polio-like syndrome with paralysis. Infection rarely results in
 death. The vaccine used in this study contains DNA that instructs the body to produce a small
 amount of a protein found in WNV. If the body creates resistance or immunity to these
 proteins, then the vaccine may protect against WNV. Study participants cannot get WNV from
 the vaccine.

 Healthy volunteers between 18 years and 50 years of age may be eligible for this study.
 Candidates are screened with a medical history, physical examination, and blood and urine
 tests, including a pregnancy test for women who can become pregnant. Patients undergo the
 following tests and procedures:

 -  Vaccine injections: Vaccines are given as injections in the upper arm, using a
 needleless system called the Biojector 2000. The first injection is on study day 0, the
 second on day 28 (+/-) 7 days, and the third on day 56 (+/-) 7 days. There must be at
 least 21 days between injections. The pregnancy test for women of childbearing potential
 is repeated the day of each vaccine injection.

 -  Diary card: Participants are given a 5-day diary card after each injection to record
 their temperature and any symptoms and side effects they may experience for up to 5 days
 after the injection. The diary cards are returned to the clinic at visits scheduled 2
 weeks after each injection. Side effects and symptoms also must be reported immediately
 to a study nurse or doctor, and a clinic visit may be required for an examination.

 -  Clinic visits: At day 0 and weeks 2, 4, 6, 8, 10, 12, 24 and 32, participants have a
 medical history, physical examination (if needed) and blood tests. Vital signs and
 weight are also recorded. Lymph nodes are examined at day 0 and weeks 2, 4, 6, 8, 10 and
 12, and urine samples are collected at day 0 and weeks 2, 4, 6, 8 and 10.

 Some of the blood drawn during this study is used for genetic tests to see if different types
 of immune response to a vaccine are related to genetic differences in people.
Study Design: This is a Phase I open label study to evaluate safety, tolerability, and immune
 response of a recombinant DNA vaccine, VRC-WNVDNA017-00-VP. The hypothesis is that this
 regimen will be safe for human administration and elicit immune responses to the West Nile
 virus. The primary objective is to evaluate the safety and tolerability in humans of the
 investigational vaccine. Secondary and exploratory objectives are related to the
 immunogenicity of the study vaccine.

 Product Description: VRC-WNVDNA017-00-VP is composed of a single closed circular DNA plasmid
 that encodes the WNV viral proteins precursor transmembrane (PrM) and envelope (E). Vaccine
 vials will be supplied at 4 mg/mL. Each DNA vaccination will be 1 mL of vaccine administered
 intramuscularly (in deltoid muscle) using the Biojector 2000 Needle-Free Injection Management
 System.

 Subjects: Healthy adult volunteers (18 to 50 years old) will be enrolled.

 Study Plan: Fifteen volunteers will be enrolled and receive 3 injections on the schedule
 shown in the schema. The protocol requires nine clinic visits and three telephone follow-up
 contacts.

 Study Duration: 32 weeks clinical follow-up for each participant.

 Study Endpoints: The primary endpoint is safety of the regimen; secondary immunogenicity
 endpoints are an ELISPOT and an intracellular cytokine staining (ICS) assay for WNV-specific
 T cell responses and a WNV ELISA assay. The principal timepoints for ICS and ELISPOT are Week
 0 (baseline), Week 8 and Week 12. ICS and ELISPOT at other study timepoints, as well as other
 immunogenicity assays through Week 32, will be completed as exploratory evaluations. Stored
 sera will be tested for WNV neutralizing antibody once an assay is developed.
-  INCLUSION CRITERIA:

 A participant must meet all of the following criteria:

 18 to 50 years old.

 Available for clinical follow-up through Week 32 of the study.

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

 Complete an Assessment of Understanding prior to enrollment and verbalize understanding of
 all questions answered incorrectly.

 Able and willing to complete the informed consent process.

 Willing to receive HIV test results and willing to abide by NIH guidelines for partner
 notification of positive HIV results.

 Willing to donate blood for sample storage to be used for future research.

 In good general health without clinically significant medical history and has
 satisfactorily completed screening.

 Physical examination and laboratory results without clinically significant findings within
 the 28 days prior to enrollment.

 Laboratory Criteria within 28 days prior to enrollment:

 Hemoglobin greater than or equal to 11.5 g/dL for women; greater than or equal to 13.5 g/dL
 for men.

 WBC = 3,300-12,000 cells/mm(3).

 Absolute neutrophil count (ANC) within institutional normal range.

 Total lymphocyte count greater than or equal to 800 cells/mm(3).

 Platelets = 125,000 - 400,000/mm(3).

 ALT (SGPT) less than or equal to 1.25 x upper limit of normal.

 Serum creatinine less than or equal to 1 x upper limit of normal (less than or equal to 1.3
 mg/dL for females; less than or equal to 1.4 mg/dL for males).

 Normal urinalysis defined as negative glucose, negative or trace protein, and no clinically
 significant blood in the urine.

 Negative FDA-approved HIV blood test.

 Negative Hepatitis B surface antigen.

 Negative anti-HCV and negative HCV PCR.

 Laboratory Criteria within 12 weeks (84 days) prior to enrollment:

 Negative flavivirus serology within 84 days prior to enrollment and no history of prior
 vaccination against yellow fever or Japanese encephalitis virus.

 Female-Specific Criteria:

 Negative Beta-HCG pregnancy test (urine or serum) on day of enrollment for women presumed
 to be of reproductive potential.

 A female participant must meet any of the following criteria:

 No reproductive potential because of menopause (one year without menses) or because of a
 hysterectomy, bilateral oophorectomy, or tubal ligation

 or

 Participant agrees to be heterosexually inactive at least 21 days prior to enrollment and
 through Week 32 of the study,

 or

 Participant agrees to consistently practice contraception at least 21 days prior to
 enrollment and through Week 32 of the study by one of the following methods:

 condoms, male or female, with or without a spermicide;

 diaphragm or cervical cap with spermicide;

 intrauterine device;

 contraceptive pills or patch, Norplant, Depo-Provera or other FDA-approved contraceptive
 method;

 male partner has previously undergone a vasectomy for which there is documentation.

 EXCLUSION CRITERIA:

 A volunteer will be excluded if one or more of the following conditions apply:

 Women:

 Woman who is breast-feeding or planning to become pregnant during the 32 weeks of study
 participation.

 Volunteer has received any of the following substances:

 Immunosuppressive medications or cytotoxic medications or inhaled corticosteroids within
 the past six months (with the exception of corticosteroid nasal spray for allergic rhinitis
 or topical corticosteroids for an acute uncomplicated dermatitis);

 Blood products within 120 days prior to HIV screening;

 Immunoglobulin within 60 days prior to HIV screening;

 Investigational research agents within 30 days prior to initial study vaccine
 administration;

 Live attenuated vaccines within 30 days prior to initial study vaccine administration;

 Medically indicated subunit or killed vaccines, e.g. influenza, pneumococcal, or allergy
 treatment with antigen injections, within 14 days of study vaccine administration;

 Current anti-TB prophylaxis or therapy.

 Volunteer has a history of any of the following clinically significant conditions:

 Serious adverse reactions to vaccines such as anaphylaxis, hives, respiratory difficulty,
 angioedema, or abdominal pain.

 Autoimmune disease or immunodeficiency.

 Asthma that is unstable or required emergent care, urgent care, hospitalization or
 intubation during the past two years or that requires the use of oral or intravenous
 corticosteroids.

 Diabetes mellitus (type I or II), with the exception of gestational diabetes.

 History of thyroidectomy or thyroid disease that required medication within the past 12
 months.

 Serious angioedema episodes within the previous 3 years or requiring medication in the
 previous two years.

 Hypertension that is not well controlled by medication or is more than 145/95 at
 enrollment.

 Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet
 disorder requiring special precautions) or significant bruising or bleeding difficulties
 with IM injections or blood draws.

 Malignancy that is active or treated malignancy for which there is not reasonable assurance
 of sustained cure or malignancy that is likely to recur during the period of the study.

 Seizure disorder other than: 1) febrile seizures under the age of two, 2) seizures
 secondary to alcohol withdrawal more than 3 years ago, or 3) a singular seizure not
 requiring treatment within the last 3 years.

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

 Allergic reaction to aminoglycoside antibiotics.

 Psychiatric condition that precludes compliance with the protocol; past or present
 psychoses; past or present bipolar disorder; disorder requiring lithium; or within five
 years prior to enrollment, a history of suicide plan or attempt.

 Any medical, psychiatric, social condition, occupational reason or other responsibility
 that, in the judgment of the investigator, is a contraindication to protocol participation
 or impairs a volunteer's ability to give informed consent.