Safety of and Immune Response to the PENNVAX-B DNA Vaccine With and Without IL-12 in HIV-uninfected Adults

An effective and safe vaccine must be developed in order to halt the HIV pandemic. The
purpose of this study is to assess the safety and immune response to the HIV DNA vaccine,
PENNVAX-B when given with and without an IL-12 adjuvant and delivered via electroporation.

Participants in this study will be randomly assigned to one of three groups and will visit
the study clinic 9 times over 9 months. Group 1 will enroll first. Participants in this
group will receive 3 mg of the PENNVAX-B or placebo vaccine at Months 0, 1, and 3. Once
safety data has been examined for Group 1, Group 2 will begin enrollment. Group 2
participants will receive 3 mg of PENNVAX-B vaccine plus 1 mg of IL-12 adjuvant or placebo
at Months 0, 1, and 3. Once Group 1 and Group 2 safety data have been collected Group 3 will
begin enrollment. These participants will also receive 3 mg of PENNVAX-B vaccine plus 1 mg
of IL-12 adjuvant or placebo at Months 0, 1, and 3.

At clinic visits participants will have physical exams and blood and urine collected. After
receiving study injections, participants will be observed in the clinic for at least 30
minutes. In addition, participants will be asked to monitor symptoms for 3 days after each
injection.

Inclusion Criteria:

- Access to a participating HVTN CRS and willingness to be followed for the planned
duration of the study

- Ability and willingness to provide informed consent

- Assessment of understanding: volunteer demonstrates understanding of this study and
the Step Study results; completes a questionnaire prior to first vaccination, with
verbal demonstration of understanding of all questionnaire items answered incorrectly

- Willing to receive HIV test results

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

- Assessed by the clinic staff as being at "low risk" for HIV infection on the basis of
behaviors within the 12 months prior to enrollment

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

- Certain laboratory values. Details on this criterion can be found in the protocol.

- Negative HIV-1 and -2 blood test: US participants must have a negative FDA-approved
enzyme immunoassay (EIA).

- 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

- Volunteers 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 volunteer who was born female must agree to consistently use
effective contraception from at least 21 days prior to enrollment through the last
required protocol clinic visit for sexual activity that could lead to pregnancy, or
not be of reproductive potential, or be sexually abstinent

- Volunteers 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:

- Within the 12 months prior to enrollment: excessive daily alcohol use or frequent
binge drinking or chronic marijuana abuse or any other illicit drug use

- Within the 12 months prior to enrollment: a history of newly acquired or diagnosed
syphilis; newly acquired gonorrhea, non-gonococcal urethritis, herpes simplex virus
type 2 (HSV2), chlamydia, pelvic inflammatory disease (PID), trichomonas,
mucopurulent cervicitis, epididymitis, proctitis, lymphogranuloma venereum, or
chancroid

- 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, documentation of the identity
of the study control/placebo must be provided to the HVTN 080 PSRT, who 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 or for those who have received control/placebo in an experimental vaccine
trial.

- 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

- 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 080 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, HPV)

- 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

- Allergy to amide-type local anesthetics

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

- A history of cardiac arrhythmia, e.g., supraventricular tachycardia, atrial
fibrillation, or frequent ectopy on exam. (Not excluded: sinus arrhythmia)

- Clinically significant medical condition, physical examination findings, clinically
significant abnormal laboratory results, or past medical history with clinically
significant implications for current health.

- 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.

- Autoimmune disease

- Immunodeficiency

- Asthma other than mild, well-controlled 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

- Angioedema within the last 3 years if episodes are considered serious or have
required medication within the last 2 years

- Hypertension

- BMI > 30 kg/m2

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

- Malignancy (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.)

- Seizure disorder

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

- Psychiatric condition that precludes compliance with the protocol

- Pregnant or breastfeeding