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

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