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
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.
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
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
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
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.,
Participant agrees to be heterosexually inactive at least 21 days prior to enrollment and
throughout the duration of the study,
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
contraceptive pills, Norplant, or Depo-Provera
male partner has previously undergone a vasectomy for which there is documentation.
A volunteer will be excluded if one or more of the following is true.
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
8. Medically indicated subunit or killed vaccines, e.g. influenza, pneumococcal, or
allergy treatment with antigen injections, within 14 days of study vaccine
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
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
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