Phase I Study of West Nile Virus Vaccine

- INCLUSION CRITERIA:

A participant must meet all of the following criteria:

1. 18 to 65 years old.

2. Available for clinical follow-up through Week 32 and contact (correspondence, telephone or e-mail) or clinical visit through Week 52 of the study.

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

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

5. Able and willing to complete the informed consent process.

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

7. Willing to donate blood for sample storage to be used for future research and genetic testing, including HLA analysis.

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

9. Physical examination and laboratory results without clinically significant findings and a body mass index (BMI) less than 40 within the 28 days prior to enrollment.

Laboratory Criteria within 28 days prior to enrollment:

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

11. White blood cell (WBC) equal to 3,300-12,000 cells/mm(3).

12. Absolute neutrophil count (ANC) within institutional normal range.

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

14. Platelets equal to 125,000 - 400,000/mm(3).

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

16. 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).

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

18. Negative FDA-approved HIV blood test. [Note: Results of HIV ELISA will be documented, but a negative HIV PCR will be sufficient for eligibility screening of subjects with positive HIV ELISA that is due to prior participation in an HIV vaccine study.]

19. Negative hepatitis B surface antigen.

20. Negative anti-HCV and negative hepatitis C virus (HCV) PCR.

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

21. Negative flavivirus serology (in the Focus Technologies WNV antibody ELISA assay) within 84 days prior to enrollment and no history of prior vaccination against yellow fever or Japanese encephalitis virus; and no history of prior vaccination against West Nile virus with an investigational vaccine.

Female-Specific Criteria:

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

23. 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

EXCLUSION CRITERIA:

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

Women:

1. Breast-feeding or planning to become pregnant during the 32 weeks of study participation.

Volunteer has received any of the following substances:

2. Immunosuppressive medications, cytotoxic medications, inhaled corticosteroids, or long-acting beta-agonists within the past six months. (Note that use of corticosteroid nasal spray for allergic rhinitis, topical corticosteroids for an acute uncomplicated dermatitis, or short-acting beta-agonists in controlled asthmatics are not excluded).

3. Blood products within 120 days prior to HIV screening.

4. Immunoglobulin within 60 days prior to HIV screening.

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

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

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

8. Current anti-TB prophylaxis or therapy.

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

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

10. Autoimmune disease or immunodeficiency.

11. 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.

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

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

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

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

16. 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.

17. 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.

18. 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.

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

20. Allergic reaction to aminoglycoside antibiotics.

21. 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.

22. 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.

23. Active smoker within the past 5 years AND with 25 pack-years or greater smoking history.

24. If age 51-65 years and with 3 or more of the 5 health risk factors noted below, the subject will be excluded:

- Current smoker (or quit smoking less than 28 days prior to enrollment)

- BMI greater than 35

- Fasting low density lipoprotein (LDL) greater than 159 mg/dL or fasting cholesterol greater than 239 mg/dL

- Systolic blood pressure greater than 140 mm Hg or diastolic blood pressure greater than 90 mm Hg

- Fasting blood glucose greater than 125 mg/dL

Note: The fasting blood tests require 8 hours fast prior to the blood draw. The results used for eligibility screening must be from tests completed no more than 12 weeks (84 days) prior to day of enrollment. The individual criteria for BMI (inclusion item 9), blood pressure (exclusion item 15) and smoking history (exclusion item 23) must also be met.