HIV-1 Vaccine Test in Uninfected Adult Volunteers
HIV-1 Vaccine Test in Uninfected Adult Volunteers
This study will test the safety of an experimental vaccine against HIV and examine whether it
 induces an immune response to HIV. A vaccine is a substance given to try to create resistance
 or immunity to a disease or infection. The vaccine in this study is made from DNA (genetic
 material) of four HIV proteins called gag, pol, Nef, and Env. Injected into a human, the
 viral DNA instructs the body to make small amounts of some HIV proteins. This study will see
 if the body then creates an immune response to these proteins. Study participants cannot
 catch HIV or AIDS from the DNA vaccine or any proteins made from it.

 Healthy normal volunteers between 18 and 60 years of age may be eligible for this study.
 Candidates will provide a medical history, including information on sexual behaviors and drug
 use. They will have a physical examination and blood and urine tests. Women will also have a
 pregnancy test. Women enrolled in the study must either be infertile (e.g., due to menopause
 or hysterectomy) or must agree either to abstain from heterosexual sex or to practice birth
 control for at least 21 days before beginning the study and throughout its duration.

 Participants will be randomly assigned to receive either the experimental vaccine or a
 placebo (a control substance made up of an inactive salt solution) and will be divided into
 three groups, based on their entry into the study. Of the first seven people enrolled (Group
 1), five will receive a 2-mg dose of vaccine and two will receive placebo. If the vaccine is
 safe at this dose, then in Group 2, five people will receive a 4-mg dose of vaccine and two
 will receive placebo. If this dose is safe, then in Group 3, thirty people will receive an
 8-mg dose of vaccine and six will receive placebo.

 All participants will receive three injections in an upper arm muscle-one injection a month
 for three months-with a needle-less device called a Biojector 2000® (Registered Trademark).
 At the time of each injection, participants will be observed for at least 1 hour after
 immunization. At home, they will record their temperature and any symptoms they may
 experience, including any effects at the injection site, for at least 2 days, or as long as
 the symptoms remain. If symptoms occur, participants will report them immediately to the
 clinic staff and, if necessary, come to the clinic for an examination.

 Participants will have about 10 clinic visits during the study. Most visits will last about 2
 hours; those on vaccination days will last about 4 hours. At each visit, participants will be
 checked for health changes or problems and will be asked about medications they are taking.
 Blood will be drawn for immune system testing. Additional laboratory tests may be requested
 between visits. Participants will be tested several times for HIV, will be questioned about
 their sexual behavior and drug use, and about social effects they may have experienced from
 their participation in the study.

 Some of the blood drawn for this study will be used to test for HLA type-a genetic test of
 immune system markers. For research, HLA testing is sometimes used to try to identify factors
 associated with the progression of HIV disease or related conditions.
This is a Phase I, randomized, controlled, double-blinded, dose-escalation study to examine
 tolerability, dose, and immune response of an HIV DNA plasmid vaccine. The hypothesis is that
 this vaccine will be safe for human administration and elicit immune responses to HIV. The
 primary objective is to evaluate the safety and tolerability in humans of VCR-HIVDNA006-00-VP
 and secondary objectives are to evaluate the immuogenicity of the vaccine and social impact
 of participating in an HIV-1 vaccine trial. A Data and Safety Monitoring Board (DSMB) will
 review protocol results twice prior to dose escalation to the 8 mg dose level.
INCLUSION CRITERIA:

 A participant must meet all of the following criteria:

 1. 18 to 60 years old.

 2. Available for follow-up for the duration of the study (12 months).

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

 4. Able and willing to sign the informed consent form.

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

 6. Willing to have blood samples used for future research.

 7. Willing to complete questionnaire to identify HIV infection risks and amendable to
 risk reduction counseling.

 8. In good general health without clinically significant medical history.

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

 Laboratory Criteria within 28 days prior to enrollment:

 10. Hematocrit greater than or equal to 34% for women; greater than or equal to 38% for
 men

 11. WBC count: Non-African Americans equals 3,300-12,000 cells/mm(3); African-Americans
 equals 2,500-12,000 cells/mm(3) (in absence of clinical or pathological etiology)

 12. Differential either within institutional normal range or accompanied by site physician
 approval

 13. Total lymphocyte count: Non-African Americans greater than or equal to 800
 cells/mm(3); African Americans greater than or equal to 650 cells/mm(3) (in the
 absence of clinical or pathological etiology)

 14. Platelets equals 125,000-550,000/mm(3)

 15. ALT (SGPT) less than or equal to 1.5 X upper limit of normal

 16. Serum creatinine less than or equal to 1.4 mg/dL

 17. Normal urinalysis defined as negative glucose, negative or trace protein, and negative
 or trace hemoglobin.

 18. Negative FDA-approved HIV blood test

 19. Negative Hepatitis B surface antigen

 20. Negative anti-HCV or negative HCV PCR if the anti-HCV is positive

 Female-Specific Criteria:

 21. Negative beta-HCG pregnancy test for women presumed to be of reproductive potential.

 22. A female participant must meet one 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
 throughout the duration of the study,

 Or

 Participant agrees to consistently practice contraception at least 21 days prior to
 enrollment and throughout the duration 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, Norplant, or Depo-Provera

 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 is true.

 Women:

 1. Woman who is breast-feeding.

 Volunteer has received any of the following substances:

 2. HIV vaccines in a prior clinical trial

 3. Immunosuppressive or cytotoxic medications within the past six months with the
 exception of corticosteroid nasal spray for allergic rhinitis or topical
 corticosteriods for an acute uncomplicated dermatitis

 4. Blood products within 120 days prior to HIV screening

 5. Immunoglobulin within 60 days prior to HIV screening

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

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

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

 9. Current anti-TB prophylaxis or therapy

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

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

 11. Autoimmune disease or immunodeficiency

 12. 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
 corticosteriods.

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

 14. Thyroid disease including history of thyroidectomy and diagnoses that required
 medication within the past 12 months.

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

 16. Hypertension that is not well controlled by medication or is more than 150/100 at
 enrollment.

 17. 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.

 18. Syphilis infection that is active or positive serology due to a syphilis infection
 treated less than six months ago.

 19. 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 is eligible.

 20. 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 prolonged treatment more than 3 years ago.

 21. Asplenia or any condition resulting in the absence or removal of the spleen.

 22. Psychiatric condition that precludes compliance with the protocol; past or present
 psychoses; past or present bipolar disorder requiring therapy that has not been well
 controlled on medication for the past two years; disorder requiring lithium; or
 suicidal ideation occurring within five years prior to enrollment.

 23. Any medical, psychiatric, or social condition, or occupational or other responsibility
 that, in the judgement of the investigator, would interfere with or serve as a
 contraindication to protocol adherence or a volunteer's ability to give informed
 consent.