This study will determine the safety and side effects of two experimental HIV vaccines given
in a "prime-boost" schedule. It will also monitor participants for the social impact of
being in an HIV vaccine study (e.g., problems with insurance, health care, friends, family,
employment, housing, and so forth). The vaccines are VRC-HIVDNA016-00-VP (called the DNA
vaccine) and VRC-HIVADV014-00-VP (called the rAd vaccine). The DNA vaccine codes for four
HIV proteins. The rAd vaccine is made using an adenovirus (a common virus that causes upper
respiratory infections, such as the common cold) that has been modified to contain DNA that
codes for three HIV proteins. These vaccines cannot cause HIV or adenoviral infections.
The study will also see if the vaccines cause an immune response; if the injection of the
DNA vaccine given using a needle and syringe is similar in safety and immune response to
giving them with a needleless injection device called a Biojector 2000; if people who
already have antibodies to adenovirus still have an immune response to rAd vaccine; and if
there are social harms that result from participating in an HIV vaccine study.
Healthy volunteers between 18 and 50 years of age may be eligible for this 42-week study.
Candidates are screened with a medical history, physical examination, blood and urine tests
(including pregnancy test for women), and questions regarding sexual behavior and other
Participants receive three injections (shots) of the DNA vaccine and one injection of the
rAd vaccine. All injections are given into a muscle in the upper arm (alternating right and
left arms with each injection), using a needle and syringe or the needleless Biojector 2000.
The first vaccination is given the day of enrollment into the study, and the DNA
vaccinations are given about 4 weeks apart from each other, with a minimum of 21 days
between injections. The rAd "booster"vaccination is given at Week 24. Participants fill out
a diary card at home for 5 days after each vaccination, recording their temperature and any
symptoms. They come to the clinic for follow-up 3 days each DNA vaccine injection, and call
or return again 7 days after each injection. They call a study nurse 1 or 2 days after the
There are 15 to 18 clinic visits during the course of the study. At each visit, participants
are checked for health changes or problems. Blood and urine samples are collected at some
visits. Participants are periodically tested for HIV and asked questions about their sexual
behavior and drug use and are counseled throughout the study on HIV risk reduction. They are
also asked about any social effects they may have experienced as a result of their
participation in this study.
Study Design: This is a Phase I randomized study to examine safety and tolerability of, as
well as immune response to, a schedule of 3 HIV DNA plasmid vaccinations followed by one HIV
adenoviral vector vaccine (rAd) booster. The hypotheses are that: 1) this regimen will be
safe for human administration and elicit immune responses to HIV-1; 2) Biojector and
Needle/Syringe are both safe to use for IM injection of the DNA vaccine and 3) subjects with
both low and high pre-existing adenovirus serotype 5 antibody (Ad5Ab) titer will have a
boost in immune response to HIV-1 peptides following the Ad booster vaccination. In this
study equal numbers of subjects with high and low Ad5Ab titers will be randomized to receive
DNA vaccinations by either needle and syringe (N/S) or by Biojector and then to receive
either 1010 PU or 1011 PU rAd booster vaccination in a factorial design. The primary
objective is to evaluate the safety and tolerability in humans of the prime-boost
vaccination regimen. Secondary objectives are related to evaluation of the immunogenicity of
the DNA vaccine when administered by N/S or Biojector, the immunogenicity of the Ad vaccine
at two different doses in subjects with high and low pre-enrollment titers of Ad5Ab, the
development of adenovirus serotype 5 neutralizing antibody and the social impact of
participating in an HIV-1 vaccine trial. Exploratory evaluations of the immunogenicity of
the prime-boost regimen are also planned. The preliminary results may serve as the basis for
designing studies to provide more definitive answers to questions about method of
administration and effect of pre-enrollment Ad5Ab titer on safety of and immune response to
the rAd booster vaccination.
Product Description: VRC-HIVDNA016-00-VP is composed of 6 closed, circular DNA plasmids that
are each 16.67% (by weight) of the vaccine. Each of the 6 plasmids in this vaccine expresses
a single gene product. Plasmids VRC 4401, VRC 4409 and VRC 4404 are designed to express
clade B HIV-1 Gag, Pol and Nef, respectively. VRC 5736, VRC 5737, and VRC 5738 are designed
to express HIV-1 Env glycoprotein from clade A, clade B, and clade C, respectively. Vaccine
vials will be supplied at 4 mg/mL. DNA vaccinations will be 1 mL of vaccine administered
intramuscularly using either N/S or the Biojector 2000 Needle-Free Injection Management
System. VRC-HIVADV014-00-VP is a recombinant product composed of four non-replicating
adenoviral vectors (in a 3:1:1:1 ratio) that code for HIV-1 Gag/Pol polyproteins from clade
B and HIV-1 Env glycoproteins from clades A, B, and C. All rAd injections will be
administered by N/S.
Subjects: Forty healthy adult volunteers, 18 to 50 years old; 20 subjects with low Ad5Ab
(1:500) and 20 subjects with high Ad5Ab (greater than 1:500).
Study Plan: Forty subjects will be randomized in a 1:1 ratio to receive the same vaccination
schedule but by two different methods of intramuscular administration (N/S or Biojector), as
shown in the schema. The rAd boost will also be randomized to be either 1010 PU or 1011 PU
in 1:1 ratio. The rAd boost dosage will be blinded until 6 weeks of safety and
immunogenicity evaluations after the rAd boost are completed for all subjects.
- INCLUSION CRITERIA:
A participant must meet all of the following criteria:
1. 18 to 50 years old.
2. Available for clinical follow-up through Week 42 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.
8. Willing to discuss HIV infection risks and amenable to risk reduction counseling.
9. In good general health without clinically significant medical history.
10. 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:
11. Hemoglobin greater than or equal to 11.5 g/dL for women; greater than or equal to
13.5 g/dL for men.
12. White blood cells (WBC) = 3,300-12,000 cells/mm(3).
13. Differential either within institutional normal range or accompanied by site
14. Total lymphocyte count greater than or equal to 800 cells/mm(3).
15. Platelets = 125,000 - 550,000/mm(3).
16. Alanine aminotransferase (ALT) less than or equal to 1.25 x upper limit of normal.
17. Serum creatinine less than or equal to upper limit of normal.
18. Normal urinalysis defined as negative glucose, negative or trace protein, and no
clinically significant blood in the urine.
19. Negative Food and Drug Administration (FDA)-approved HIV blood test.
20. Negative Hepatitis B surface antigen.
21. Negative anti-HCV (hepatitis C virus antibody) and negative HCV PCR.
22. Negative beta-HCG (human chorionic gonadotropin) 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,
Participant agrees to be heterosexually inactive at least 21 days prior to enrollment and
through Week 42 of the study,
Participant agrees to consistently practice contraception at least 21 days prior to
enrollment and through Week 42 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
- 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:
1. Woman who is breast-feeding or planning to become pregnant during the 42 weeks of
Volunteer has received any of the following substances:
2. HIV vaccine in a prior clinical trial.
3. 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).
4. Blood products within 120 days prior to HIV screening.
5. Immunoglobulin within 60 days prior to HIV screening.
6. Investigational research agents within 30 days prior to initial study vaccine
7. Live attenuated vaccines 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-tuberculosis prophylaxis or therapy.
Volunteer has a history of any of the following clinically significant conditions:
10. Serious adverse reactions to 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. History of thyroidectomy or thyroid disease that required medication within the past
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 145/95 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 a 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.
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 treatment within the last 3 years.
21. Asplenia, functional asplenia or any condition resulting in the absence or removal of
22. 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, history of a suicide plan or attempt.
23. 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.
24. A subject with 3 or more of the 5 health risk factors noted below 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 10) and
blood pressure (exclusion item 16) must also be met.