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
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
- 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
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
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.
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
Participant agrees to be heterosexually inactive at least 21 days prior to enrollment and
through Week 32 of the study,
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;
contraceptive pills or patch, Norplant, Depo-Provera or other FDA-approved contraceptive
male partner has previously undergone a vasectomy for which there is documentation.
A volunteer will be excluded if one or more of the following conditions apply:
Woman who is breast-feeding or planning to become pregnant during the 32 weeks of study
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
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
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
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
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
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
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.