Evaluating the Safety of and Immune Response to HIV-MAG DNA Vaccine With or Without Plasmid IL-12 Adjuvant Delivered Intramuscularly Via Electroporation Followed by VSV-gag HIV Vaccine Boost in Healthy, HIV-Uninfected Adults
Evaluating the Safety of and Immune Response to HIV-MAG DNA Vaccine With or Without Plasmid IL-12 Adjuvant Delivered Intramuscularly Via Electroporation Followed by VSV-gag HIV Vaccine Boost in Healthy, HIV-Uninfected Adults
Some vaccines may work better when given together with another substance known as an adjuvant
 or when given with an experimental procedure called electroporation (EP). EP is a method
 where an electric pulse is administered to the same muscle where the vaccine injection is
 given. The addition of the adjuvant to the vaccine and the delivery with EP may increase a
 person's immune response to the vaccine. Combination approaches such as a DNA vaccine
 followed by live vector boost may also increase a person's immune response to the vaccine
 components. All of these interventions will be tested in this study.

 This study will evaluate the safety and tolerability of and immune response to an HIV DNA
 vaccine with or without plasmid IL-12 adjuvant, when given by EP and followed by a live
 vector vaccine given IM by needle and syringe in healthy, HIV-uninfected adults.
The effectiveness of a vaccine may be increased when combined with an adjuvant and/or when
 given with EP. The addition of an adjuvant or EP may increase a person's immune response to a
 vaccine. Furthermore, the immune response to HIV antigens may be improved by giving a DNA
 vaccine boosted with a live vector vaccine. The purpose of this study is to evaluate the
 safety, tolerability, and immunogenicity of an HIV DNA vaccine (HIV-MAG) alone or in
 combination with an IL-12 pDNA adjuvant, delivered IM via EP followed by a Vesicular
 Stomatitis Virus (VSV) HIV gag vaccine boost given IM by needle and syringe in healthy,
 HIV-uninfected adults.

 Participants will be enrolled into the study in one of four groups. Each of the four groups
 will receive 3 mg of the HIV-MAG vaccine alone or combined with one of three different doses
 of the IL-12 pDNA adjuvant, followed by the VSV HIV gag vaccine boost. Within each of the
 four groups, participants will be randomly assigned to receive the study vaccines or placebo.
 At study entry (Day 0), all participants will undergo a physical examination and blood
 collection. Female participants will also take a pregnancy test. Participants will complete
 questionnaires and receive counseling on HIV risk reduction. They will also receive their
 first vaccination. Participants will remain in the clinic for 30 minutes after the
 vaccination for observation and monitoring.

 Additional vaccination study visits will occur at Months 1, 3, and 6. At Months 1 and 3,
 participants will receive the same vaccine or placebo they received at study entry; at Month
 6, participants will receive the VSV HIV gag vaccine or placebo. For 3 days after the study
 entry and Months 1 and 3 vaccination visits, participants will record their symptoms in a
 diary. After the Month 6 vaccination visit, participants will record their symptoms for 7
 days.

 Participants in Groups 1 and 3 will attend additional study visits on Days 1, 3, 14, 42, 91,
 98, 169, 171, 175, 182, 273, and 364. Participants in Groups 2 and 4 will attend additional
 study visits on Days 14, 42, 98, 182, 273, and 364. Most study visits will include a physical
 examination, blood collection, oral mucosa examination, interviews and questionnaires, and
 oral mucosa examination. If participant has any oral sores, oral swabs may be collected.
 Saliva also may be collected. Select study visits will include a mini mental state exam,
 urine collection, HIV testing, and risk reduction counseling. Study researchers will contact
 participants at Months 15, 24, and 36 for follow-up health monitoring.
Inclusion Criteria:

 -  Access to a participating HIV Vaccine Trials Network (HVTN) clinical research site
 (CRS) and willing to be followed for the planned duration of the study

 -  Able and willing to provide informed consent

 -  Assessment of understanding: participant demonstrates understanding of this study and
 completes a questionnaire prior to the first vaccination with verbal demonstration of
 understanding of all questionnaire items answered incorrectly

 -  Willing to receive HIV test results

 -  Willing to discuss HIV infection risks, amenable to HIV risk reduction counseling, and
 committed to maintaining behavior consistent with low risk of HIV exposure through the
 last required protocol clinic visit

 -  Willing to be contacted annually after completion of scheduled clinic visits for a
 total of 3 years following initial study injection

 -  Agrees not to enroll in another study of an investigational research agent prior to
 completion of last required protocol clinic visit (excludes annual contacts for safety
 surveillance)

 -  In good general health as shown by medical history, physical exam, and screening
 laboratory tests

 -  Assessed by the clinic staff as being at "low risk" for HIV infection

 -  Hemoglobin greater than or equal to 11.0 g/dL for participants who were born female;
 greater than or equal to 13.0 g/dL for participants who were born male

 -  White blood cell (WBC) count equal to 3,300 to 12,000 cells/mm^3

 -  Total lymphocyte count greater than or equal to 800 cells/mm^3

 -  Remaining differential either within institutional normal range or with site physician
 approval

 -  Platelets equal to 125,000 to 550,000/mm^3

 -  Chemistry panel: ALT, AST, alkaline phosphatase, and creatinine values less than or
 equal to the institutional upper limits of normal; CPK less than or equal to 2.0 times
 the institutional upper limit of normal

 -  Negative HIV-1 and -2 blood test: participants in the United States must have a
 negative Food and Drug Administration (FDA)-approved immunoassay

 -  Negative hepatitis B surface antigen (HBsAg)

 -  Negative anti-hepatitis C virus antibodies (anti-HCV), or negative HCV polymerase
 chain reaction (PCR) if the anti-HCV is positive

 -  Normal urine:

 1. Negative urine glucose, and

 2. Negative or trace urine protein, and

 3. Negative or trace urine hemoglobin (if trace hemoglobin is present on dipstick, a
 microscopic urinalysis within institutional normal range)

 -  Participants who were born female: negative serum or urine beta human chorionic
 gonadotropin (β-HCG) pregnancy test performed prior to vaccination on the day of
 initial vaccination

 -  Reproductive status: A participant who was born female must agree to consistently use
 effective contraception for sexual activity that could lead to pregnancy from at least
 21 days prior to enrollment through the last required protocol clinic visit; or not be
 of reproductive potential, such as having reached menopause (no menses for 1 year) or
 having undergone hysterectomy, bilateral oophorectomy, or tubal ligation; or be
 sexually abstinent. More information on this criterion can be found in the protocol.

 -  Participants who were born female must also agree not to seek pregnancy through
 alternative methods, such as artificial insemination or in vitro fertilization until
 after the last required protocol clinic visit

 Exclusion Criteria:

 -  Allergy to amide-type local anesthetics (bupivacaine [Marcaine], lidocaine
 [Xylocaine], mepivacaine [Polocaine/Carbocaine], etidocaine [Duranest], prilocaine
 [Citanest, EMLA® cream])

 -  Presence of implanted electronic medical device (e.g., pacemaker, implantable
 cardioverter defibrillator)

 -  Presence of surgical or traumatic metal implant in the upper limb and/or upper torso

 -  Sinus bradycardia (defined as less than 50 bpm on exam) or a history of cardiac
 arrhythmia: e.g., supraventricular tachycardia, atrial fibrillation, or frequent
 ectopy

 -  Neurological or neuropsychiatric disorder that may interfere with the assessment of
 safety: e.g., frequent recurring headaches (i.e., a pattern of more than one headache
 per month affecting activities of daily living [ADLs]/work, frequent or
 severe/complicated migraines, cluster headaches), a chronic pain syndrome, dizziness,
 history of meningitis or encephalitis, cranial/spinal/peripheral neuropathy, limb
 weakness or paralysis, movement disorder, narcolepsy, stroke with sequelae,
 moderate/severe major depressive disorder, moderate/severe bipolar disorder

 -  Seizure disorder

 -  Untreated or incompletely treated syphilis infection

 -  HIV vaccine(s) received in a prior HIV vaccine trial. For potential participants who
 have received control/placebo in an HIV vaccine trial, the HVTN 087 Protocol Safety
 Review Team (PSRT) will determine eligibility on a case-by-case basis.

 -  Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine
 trial. Exceptions may be made for vaccines that have subsequently undergone licensure
 by the FDA. For potential participants who have received control/placebo in an
 experimental vaccine trial, the HVTN 087 PSRT will determine eligibility on a
 case-by-case basis. For potential participants who have received an experimental
 vaccine(s) greater than 5 years ago, eligibility for enrollment will be determined by
 the PSRT on a case-by-case basis.

 -  Immunosuppressive medications received within 168 days before first vaccination. (Not
 excluded: [1] corticosteroid nasal spray for allergic rhinitis; [2] topical
 corticosteroids for mild, uncomplicated dermatitis; or [3] oral/parenteral
 corticosteroids given for non-chronic conditions not expected to recur [length of
 therapy 10 days or less with completion at least 30 days prior to enrollment].)

 -  Blood products received within 120 days before first vaccination

 -  Immunoglobulin received within 60 days before first vaccination

 -  Live attenuated vaccines other than influenza vaccine received within 30 days before
 first vaccination or scheduled within 14 days after injection (e.g., measles, mumps,
 and rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow fever)

 -  Investigational research agents received within 30 days before first vaccination

 -  Intent to participate in another study of an investigational research agent during the
 planned duration of the HVTN 087 study

 -  Influenza vaccine or any vaccines that are not live attenuated vaccines and were
 received within 14 days prior to first vaccination (e.g., tetanus, pneumococcal,
 hepatitis A or B)

 -  Allergy treatment with antigen injections within 30 days before first vaccination or
 that are scheduled within 14 days after first vaccination

 -  Current anti-tuberculosis (TB) prophylaxis or therapy

 -  Clinically significant medical condition, physical examination findings, clinically
 significant abnormal laboratory results, or past medical history with clinically
 significant implications for current health. More information on this criterion can be
 found in the protocol.

 -  Any medical, psychiatric, occupational, or other condition that, in the judgment of
 the investigator, would interfere with, or serve as a contraindication to, protocol
 adherence, assessment of safety or reactogenicity, or a participant's ability to give
 informed consent

 -  Serious adverse reactions to vaccines, including anaphylaxis and related symptoms such
 as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not excluded: a
 participant who had a nonanaphylactic adverse reaction to pertussis vaccine as a
 child.)

 -  Autoimmune disease

 -  Immunodeficiency

 -  Asthma other than mild, well-controlled asthma. More information on this criterion can
 be found in the protocol.

 -  Diabetes mellitus type 1 or type 2, including cases controlled with diet alone. (Not
 excluded: history of isolated gestational diabetes.)

 -  Thyroidectomy, or thyroid disease requiring medication during the last 12 months

 -  History of hereditary angioedema, acquired angioedema, or idiopathic angioedema

 -  Hypertension:

 1. If a person has been found to have elevated blood pressure or hypertension during
 screening or previously, exclude for blood pressure that is not well controlled.
 Well-controlled blood pressure is defined as consistently less than or equal to
 140 mm Hg systolic and less than or equal to 90 mm Hg diastolic, with or without
 medication, with only isolated, brief instances of higher readings, which must be
 less than or equal to 150 mm Hg systolic and less than or equal to 100 mm Hg
 diastolic. For these participants, blood pressure must be less than or equal to
 140 mm Hg systolic and less than or equal to 90 mm Hg diastolic at enrollment.

 2. If a person has NOT been found to have elevated blood pressure or hypertension
 during screening or previously, exclude for systolic blood pressure greater than
 or equal to 150 mm Hg at enrollment or diastolic blood pressure greater than or
 equal to 100 mm Hg at enrollment.

 -  Body mass index (BMI) greater than or equal to 40; or BMI greater than or equal to 35
 with two or more of the following: age greater than 45 years old, systolic blood
 pressure greater than 140 mm Hg, diastolic blood pressure greater than 90 mm Hg,
 current smoker, or known hyperlipidemia

 -  Deltoid skin fold measurement by caliper greater than 40 mm

 -  Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy,
 platelet disorder requiring special precautions)

 -  Cancer (Not excluded: a participant with a surgical excision and subsequent
 observation period that in the investigator's estimation has a reasonable assurance of
 sustained cure or is unlikely to recur during the period of the study.)

 -  Asplenia: any condition resulting in the absence of a functional spleen

 -  Psychiatric condition that precludes compliance with the protocol. Specifically
 excluded are people with psychoses within the past 3 years, ongoing risk for suicide,
 or history of suicide attempt or gesture within the past 3 years.

 -  Pregnant or breastfeeding