This study will test the safety of an experimental vaccine against HIV and will examine
whether it causes an immune response to HIV virus proteins. A vaccine is 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 two HIV proteins called "gag" and "pol." 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 proteins that may be made from
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 activity and drug
use. They will have a physical examination, blood tests, urine test and chest X-ray. All
candidates enrolled in the study must use a barrier method of contraception for sexual
intercourse from the start of the study until 3 months after the last vaccination.
Participants will be assigned to one of two treatment groups: one will receive the
experimental vaccine; the other will receive a control substance (inactive salt solution).
The first five people assigned to the vaccine group will receive the lowest study dose of
the vaccine. If this dose is safe, it will be increased three times for the next group of
five and then eight times for the last group of five. Each group will have a total of seven
people - five will receive the vaccine and two will get the salt solution.
Before the first injection, and possibly the second and third, a catheter (thin plastic
tube) will be placed into a vein so that treatment can be given quickly if there is a
reaction to the vaccine. 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.
For each injection, the volunteer will
- be observed for at least 1 hour after immunization
- record temperature and symptoms, including any effects at the injection site, for 2
days and report them to the clinic staff
- immediately report any side effects to a study physician or nurse.
Volunteers will have physical examinations and laboratory tests at certain times while they
receive the vaccine and for a period afterwards. These procedures will require about 14
clinic visits of about 1 to 2 hours each, and up to 6 hours on vaccination days. Blood will
be drawn at all visits. Some of the blood will be used for genetic tests, and some will be
stored for future tests of the immune system and the body's response to the study vaccine.
The study will last about 12 months from the date of the first injection. After it is
completed, clinic staff may contact volunteers once or twice a year for at least 3 years to
This is a Phase I randomized, controlled, double-blinded dose escalation study to examine
toxicity, dose and immune response of an HIV plasmid DNA vaccine. The vector used in this
study has been optimized for improved safety, expression and immunogenicity. We hypothesize
that this vaccine will elicit immune responses to HIV. All work will be conducted at the
National Institutes of Health.
Healthy, HIV-negative volunteers will be recruited and pre-screened to confirm that they
meet all of the eligibility requirements for participation. Educational materials on DNA
vaccines will be reviewed with and provided to participants before enrollment into the
study. There will be 3 groups of 7 volunteers. Each group will receive a constant dose of
the vaccine pGag(del fs)Pol delta PR delta RT delta IN/h (5 people) or a phosphate buffered
saline (PBS) control (2 people) by intramuscular inoculation. Once safety has been
established, successive groups will receive a higher dose. Study groups will receive three
immunizations containing either 0.5 mg (Group 1), 1.5 mg (Group 2), or 4.0 mg (Group 3) of a
DNA vaccine. Dose escalation will be initiated 5 weeks after the last volunteer in the
previous dose group receives their first inoculation, providing there are no significant
Vaccine-related adverse reactions will be evaluated at scheduled study visits and by study
participant report. Immune response will be evaluated as described in Appendix II.
Specimens to evaluate immunogenicity will be taken at baseline, and at the time points
indicated in Appendix VIII. Unless contraindicated, subsequent inoculations using repeat
plasmid vaccinations will be given 28 and 56 days after the first vaccinations. The
estimated duration for each volunteer to complete immunizations and follow-up is 12 months.
Participants must be between 18-60 years of age (no more than 10% of the volunteers to be
Male and female subjects are eligible. (For female participants: negative pregnancy test
at the screening visit; for both male and female participants: agree to practice
abstinence or use barrier contraception from the date of the first vaccination until 3
months after the final immunization.)
No significant findings on medical history, physical exam or screening lab studies as
determined by clinic personnel
Willing to identify HIV infection risks and amenable to risk reduction counceling.
All subjects must understand the basis of transmission of HIV and agree to abstain from
higher risk behavior for HIV infection.
Normal complete blood count and differential defined as:
Hematocrit greater than or equal to 34 percent for women and 38 percent for men; White
blood cell count greater than or equal to 3,500/mm(3) and less than or equal to
10,000/mm(3) with no significant findings on differential; Total lymphocyte count greater
than or equal to 800 cells/mm(3); Absolute CD4 count greater than or equal 400
cells/mm(3); Platelets 150,000-550,000 cells/cm(3).
Normal ALT and AST (less than or equal to 1.5 times institutional upper limit) and
creatinine (less than or equal to 1.6 mg/dl).
Normal or low positive ANA titer (1 to 3 EU) if there is no clinical evidence of
underlying disorders that are associated with a positive ANA, if no first degree relative
has an autoimmune disease, and if anti-ENA antibodies are negative
Negative anti-dsDNA antibodies
Normal IgG levels
CPK less or equal to 2 times institutional upper limit
No significant findings on urinalysis
No significant findings on chest x-ray
Negative RPR (unless determined to be a false positive or a positive result is due to a
prior-greater than 6 month-treated infection)
Negative for Hepatitis B surface antigen and anti-hepatitis C antibody
Negative for HIV by ELISA and DNA-PCR (below the limit of detection of the assay used)
within 4 weeks of immunization (note that if a potential subject will not be allowed on
study until further studies--potentially including repeat ELISAs, RT-PCR and DNA
PCR--demonstrate that the subject is not infected with HIV)
Availability for follow-up for planned duration of the study (12 months)
Give informed consent by signing the Institutional Review Board (IRB) approved informed
Willingness to have samples stored and to have HLA testing
History of immunodeficiency, chronic illness, malignancy, autoimmune disease, or use of
immunosuppressive medications. Individuals with a history of cancer unless there has been
surgical excision followed by a sufficient observation period to give a reasonable
assurance of cure
Medical or psychiatric conditions which preclude subject compliance with the protocol.
Evidence of active drug or alcohol abuse
Tested positive to HIV at any time.
Live attenuated vaccines (including but not limited to measles, mumps, rubella and BCG)
within 60 days of study (note: medically indicated subunit or killed vaccines (e.g.,
influenza, pneumococcal) are not exclusionary, but should be given at least 2 weeks away
from HIV immunization)
Use of experimental agents within 30 days prior to study
Receipt of blood products or immunoglobulin in the past 6 months
Any history of anaphylaxis or history of other serious adverse reactions to vaccines
Prior receipt of HIV-1 vaccines
Pregnant or lactating women
Acute infectious illnesses within 1 month prior to initiation of immunization
History of splenectomy
Seizure disorder. A participant with a remote history (over 3 years) of seizure who have
not received medications for 3 years or over are eligible if: 1. the seizures were
febrile seizures under the age of 2; 2. secondary to alcohol withdrawal; or 3. it was a
Treatment with immunomodulators, except for NSAIDS, within 14 days prior to enrollment
Skin disease (e.g., eczema, psoriasis) affecting areas of immunization that precludes