Evaluating the Safety and Immunogenicity of PENNVAX®-GP DNA Vaccine and IL-12 Plasmid, Delivered Via Intradermal or Intramuscular Electroporation in Healthy, HIV-Uninfected Adults

The purpose of this study is to evaluate the safety and tolerability of the PENNVAX®-GP HIV-1
DNA vaccine and IL-12 DNA adjuvant, given by intradermal (ID) or intramuscular (IM) injection
with electroporation (EP), in healthy, HIV-uninfected adults. All study injections will be
given using an EP device, which uses an electric pulse to briefly open tiny pores in the
cells. Researchers will evaluate whether EP increases the immune response to the vaccine.

The study will enroll participants in four groups. Within each group, participants will be
randomly assigned to receive the PENNVAX®-GP DNA vaccine/IL-12 DNA adjuvant or placebo. Each
group will receive different doses of the vaccine. Enrollment will begin with Group 1, which
will receive a low dose of the vaccine and adjuvant. Study staff will review safety data from
Group 1 before enrolling people in Groups 2, 3, and 4 at higher doses. Participants in all
groups will receive injections at study entry (Day 0) and Months 1, 3, and 6. At each
injection visit, participants in Groups 1 and 4 will receive injections in one arm, and
participants in Groups 2 and 3 will receive injections in both arms. Groups 1, 2, and 3 will
receive ID injections, and Group 4 will receive IM injections.

Participants will attend study visits at Day 0, Week 2, and Months 1, 1.5, 3, 3.5, 6, 6.5, 9,
and 12. Visits will include physical examinations, urine collection, blood collection, HIV
and risk reduction counseling, and assessments and questionnaires. Some participants may have
photographs taken of the injection site (this is optional). Study staff will contact
participants at Month 18 for follow-up health monitoring.

Inclusion Criteria:

General and Demographic Criteria:

- Age of 18 to 55 years

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

- Ability and willingness to provide informed consent

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

- Agrees not to enroll in another study of an investigational research agent

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

HIV-Related Criteria:

- Willingness to receive HIV test results

- Willingness to discuss HIV infection risks and amenable to HIV risk reduction
counseling

- Assessed by the clinic staff as being at "low risk" for HIV infection and committed to
maintaining behavior consistent with low risk of HIV exposure through the last
required protocol clinic visit

Laboratory Inclusion Values:

Hemogram/Complete Blood Count (CBC)

- 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 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

- Chemistry panel: alanine aminotransferase (ALT), aspartate aminotransferase (AST), and
alkaline phosphatase less than 1.25 times the institutional upper limit of normal;
creatinine less than or equal to institutional upper limit of normal; creatine
phosphokinase (CPK) less than or equal to 2.0 times the institutional upper limit of
normal.

Virology

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

- Negative hepatitis B surface antigen (HBsAg)

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

Urine

- Normal urine:

- Negative urine glucose, and

- Negative or trace urine protein, and

- Negative or trace urine hemoglobin (if trace hemoglobin is present on dipstick, a
microscopic urinalysis with red blood cells levels within institutional normal
range).

Reproductive Status:

- Participants who were born female: negative serum or urine beta human chorionic
gonadotropin pregnancy test performed prior to vaccination on the day of initial
vaccination. Persons who are NOT of reproductive potential due to having undergone
total hysterectomy or bilateral oophorectomy (verified by medical records), are not
required to undergo pregnancy testing.

- A participant who was born female must:

- Agree to consistently use effective contraception (see Appendix B of the
protocol) for sexual activity that could lead to pregnancy from at least 21 days
prior to enrollment through the last required protocol clinic visit. More
information on this criterion is available in the protocol.

- 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.

- 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:

General:

- Blood products received within 120 days before first vaccination

- Investigational research agents received within 30 days before first vaccination

- Body mass index (BMI) greater than or equal to 40; or BMI greater than or equal to 35
with 2 or more of the following: age greater than 45, systolic blood pressure greater
than 140 mm Hg, diastolic blood pressure greater than 90 mm Hg, current smoker, known
hyperlipidemia

- Intent to participate in another study of an investigational research agent during the
planned duration of the HVTN 098 study

- Pregnant or breastfeeding

- Subcutaneous contraceptive device

Vaccines and Other Injections:

- HIV vaccine(s) received in a prior HIV vaccine trial. For participants who have
received control/placebo in an HIV vaccine trial, the HVTN 098 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 participants who have received control/placebo in an experimental
vaccine trial, the HVTN 098 PSRT will determine eligibility on a case-by-case basis.
For participants who have received an experimental vaccine(s) greater than 5 years
ago, eligibility for enrollment will be determined by the HVTN 098 PSRT on a
case-by-case basis.

- 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)

- 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

Immune System:

- Immunosuppressive medications received within 168 days before first vaccination. (Not
excluded: [1] corticosteroid nasal spray; [2] low-dose inhaled corticosteroids; [3]
topical corticosteroids for mild, uncomplicated dermatitis; or [4] a single course of
oral/parenteral corticosteroids at doses less than 2 mg/kg/day and length of therapy
less than 11 days with completion at least 30 days prior to enrollment.

- Serious adverse reactions to vaccines, including history of 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.)

- Immunoglobulin received within 60 days before first vaccination

- Autoimmune disease

- Immunodeficiency

Clinically Significant Medical Conditions:

- History or presence of keloid scar formation or hypertrophic scar

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

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

- History of cardiac arrhythmia (e.g., supraventricular tachycardia, atrial
fibrillation, or frequent ectopy)

- Untreated or incompletely treated syphilis infection

- 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 is
available 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. For example:

- Tattoo overlying the injection site

- Skin conditions at the injection site

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

- Current anti-tuberculosis prophylaxis or therapy

- Asthma exclusion criteria:

- Asthma other than mild, well-controlled asthma. (Symptoms of asthma severity as
defined in the most recent National Asthma Education and Prevention Program
Expert Panel report).

- Exclude a participant who:

- Uses a short-acting rescue inhaler (typically a beta 2 agonist) daily, or

- Uses moderate/high dose inhaled corticosteroids, or

- In the past year has either of the following: 1) Greater than 1 exacerbation of
symptoms treated with oral/parenteral corticosteroids; 2) Needed emergency care,
urgent care, hospitalization, or intubation for asthma.

- 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

- Hypertension:

- 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.

- 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

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

- Malignancy (Not excluded: participant who has had malignancy excised surgically and
who, in the investigator's estimation, has a reasonable assurance of sustained cure,
or who is unlikely to experience recurrence of malignancy during the period of the
study)

- Seizure disorder: History of seizure(s) within past three years. Also exclude if
participant has used medications in order to prevent or treat seizure(s) at any time
within the past 3 years.

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

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