Candidate HIV Vaccine
Candidate HIV Vaccine
This study will evaluate whether an experimental vaccine intended to prevent HIV infection is
 safe and whether it causes any side effects. It will also examine whether the vaccine, called
 VRC-HIVDNA016-00-VP, causes an immune response, and will monitor participants for the social
 impact of being in an HIV vaccine study. VRC-HIVDNA016-00-VP contains synthetic DNA that
 codes for parts of four HIV proteins. It also contains a "promoter" piece of DNA that is
 needed to start protein production. The promoter DNA is also synthetic and is like the
 promoter in another virus called cytomegalovirus (CMV). The vaccine contains no live HIV
 virus or CMV and cannot cause either of these illnesses.

 Healthy volunteers between 18 and 44 years old who are HIV-negative may be eligible for this
 32-week study. Candidates are screened with a medical history, physical examination, and
 blood and urine tests.

 Participants receive three injections of the experimental vaccine approximately 28 days
 apart. The injections are given with a system called the Biojector 2000 that delivers the
 vaccine through the skin into the muscle without the use of a needle. Subjects are observed
 for side effects for at least 30 minutes after each vaccination and are required to telephone
 the clinic staff 1 to 2 days after the injection to report how they are doing. In addition,
 they are given a diary card to take home, on which they record their temperature and any
 symptoms daily for five days.

 Participants return to the clinic two weeks after each injection. They return the completed
 diary card and are checked for any health changes or problems since the last visit. They are
 asked how they are feeling and what medications, if any, they have taken. Blood and urine
 samples are collected. Some subjects may be asked to have laboratory tests between regular
 visits if needed to evaluate a change in health. Participants are also asked about any social
 effects they may have experienced as a result of their participation in the study.
Study Design: This is a Phase I open label study to evaluate safety, tolerability, and immune
 response of a 6-plasmid multiclade HIV-1 DNA vaccine, VRC-HIVDNA016-00-VP. The hypothesis is
 that this regimen will be safe for human administration and elicit immune responses to HIV-1
 clade B Gag, Pol and Nef proteins, as well as clades A, B and C Env proteins. The primary
 objective is to evaluate the safety and tolerability in humans of the investigational vaccine
 and secondary objectives are to evaluate the immunogenicity of the vaccine as measured by
 intracellular cytokine staining (ICS) in the 4 weeks after the second or third dose of
 vaccine and the social impact of participating in an HIV-1 vaccine trial.

 Product Description: VRC-HIVDNA016-00-VP is composed of 6 closed, circular DNA plasmids that
 are each 16.67 percent (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. Each DNA vaccination will be 1 mL of vaccine
 administered intramuscularly (in deltoid muscle) using the Biojector 2000 Needle-Free
 Injection Management System.

 Subjects: Healthy adult volunteers (18 to 44 years old) will be enrolled.

 Study Plan: Fifteen volunteers will be enrolled, as shown in the schema:

 Name of Vaccine: VRC-HIVDNA016-00-VP

 Number of Subjects: 15

 Vaccine Injection Schedule: (at least 21 days between injections)

 Day 0: 4 mg

 Day 28 plus or minus 7: 4 mg

 Day 56 plus or minus 7: 4 mg

 Study Duration: 32 weeks clinical follow-up for each participant.

 Study Endpoints: The primary endpoint is safety of the regimen; secondary endpoints are

 cellular immune responses as measured by ICS within the first 4 weeks after the second and

 third doses and social impact at Week 32. Exploratory analyses will include HIV-specific

 antibody assays, ICS or other immunological assays at intervals between Day 0 and Week 32.
-  INCLUSION CRITERIA:

 A participant must meet all of the following criteria:

 18 to 44 years old.

 Available for clinical follow-up through Week 32 of the study.

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

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

 Able and willing to complete the informed consent process.

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

 Willing to donate blood for sample storage to be used for future research.

 Willing to discuss HIV infection risks and amenable to risk reduction counseling.

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

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

 Laboratory Criteria within 28 days prior to enrollment:

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

 WBC equal to 3,300-12,000 cells/mm(3).

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

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

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

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

 Serum creatinine less than or equal to upper limit of normal.

 Normal urinalysis defined as negative glucose, negative or trace protein, and negative or
 trace hemoglobin (blood).

 Negative FDA-approved HIV blood test.

 Negative Hepatitis B surface antigen.

 Negative anti-HCV.

 Female Specific Criteria:

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

 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 for which there is documentation.

 EXCLUSION CRITERIA:

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

 Women:

 Woman who is breast-feeding or planning to become pregnant during the 32 weeks of study
 participation.

 Volunteer has received any of the following substances:

 HIV vaccines in a prior clinical trial;

 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);

 Blood products within 120 days prior to HIV screening;

 Immunoglobulin within 60 days prior to HIV screening;

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

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

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

 Current anti-TB prophylaxis or therapy.

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

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

 Autoimmune disease or immunodeficiency.

 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.

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

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

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

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

 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.

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

 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.

 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.

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

 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.

 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.