This study evaluates whether INO-4212 and its components INO-4201 and INO-4202 administered intramuscularly (IM) or intradermally (ID) followed by electroporation (EP) will be well tolerated and immunogenic.

This study will test the safety, tolerability, and immunogenicity of the DNA vaccine, INO-4212 and its components INO-4201 and INO-4202 in healthy volunteers. INO-4201 contains the DNA sequence that codes for past Ebola Zaire virus outbreak strains, and INO-4202 contains the DNA sequence that codes for the current Ebola virus outbreak strain. When given together, the DNA vaccine is called INO-4212 and contains the DNA sequence of both the previous and the current outbreak strain. Another ingredient called INO-9012 which contains the DNA sequence for interleukin-12, will be given in a subset of subjects to help boost the body's immune response when given with the vaccine.

Following administration of vaccine, a specialized medical device, CELLECTRA®, will deliver brief electrical pulses in a process known as electroporation (EP), to help move more DNA into cells more efficiently. The study will evaluate whether INO-4212 and its components may be able to generate protective immunity against Ebola Zaire, evaluate the relative ability of IM versus ID administration to elicit immune responses and evaluate whether vaccine administered with INO-9012 can generate greater immune responses.

The Ebola vaccine under study will be tested in approximately 240 healthy adult volunteers.

Inclusion Criteria:

• Age 18-50 years;
• Able to provide consent to participate and having signed an Informed Consent Form (ICF);
• Able and willing to comply with all study procedures;
• Women of child-bearing potential who are in a relationship that could result in pregnancy agree to either remain sexually abstinent, use medically effective contraception (oral contraception, barrier methods, spermicide, etc.) or have a partner who is sterile from enrollment to 3 months following the last injection; OR, sexually active men who are considered sexually fertile must agree to use either a barrier method of contraception during the study, and agree to continue the use for at least 3 months following the last injection, or have a partner who is permanently sterile or unable to become pregnant;
• Normal screening ECG or screening ECG with no clinically significant findings;
• Screening laboratory (Complete blood count (CBC), serum electrolytes, blood urea nitrogen (BUN), creatinine (Cr), glucose, ALT, CPK, urinalysis) grade 0-1 within 30 days prior to administration of study treatment;
• No history of clinically significant immunosuppressive or autoimmune disease.

Exclusion Criteria:

• Administration of an investigational compound either currently or within 30 days of first dose;
• Previous receipt of an investigational product in an interventional trial for the treatment or prevention of Ebola (exceptions: verified receipt of placebo only or participation in an observational study);
• History of or positive serologic test for HIV, hepatitis B surface antigen (HBsAg); or any potentially communicable infectious disease as determined by the Principal Investigator or Medical Monitor;
• Positive serologic test for hepatitis C (exception: successful treatment with confirmation of sustained virologic response);
• Baseline creatinine greater than 1.5 (CKD Stage II or greater);
• Chronic liver disease or cirrhosis;
• Immunosuppressive illness including hematologic malignancy, history of solid organ or bone marrow transplantation;
• Any pre-excitation syndromes, e.g., Wolff-Parkinson-White syndrome;
• Prior major surgery or radiation therapy within 4 weeks of randomization;
• Pregnant, breast feeding, or considering becoming pregnant;
• Less than two acceptable sites exist for intramuscular or intradermal injection and EP between use of the deltoid and lateral quadriceps muscles. A site for injection/EP is not acceptable if there are tattoos, keloids or hypertrophic scars within 2 cm of the injection/EP site.
• Subject has significant acute or chronic medical illness if deemed by the practitioner that electroporation treatment could negatively impact the illness
• Subject has unstable or life-threatening cardiac disease (e.g. unstable angina, class 3 or higher congestive heart failure)
• Subject has an acute or chronic bleeding or clotting disorder that would contraindicate IM injections or use of blood thinners (e.g. anticoagulants or antiplatelet drugs) within 2 weeks;
• Subject has a cardioverter-defibrillator or pacemaker (to prevent a life-threatening arrhythmia) that is located ipsilateral to the intended deltoid injection site (unless deemed acceptable by a Cardiologist);
• Subject has metal implant or implantable medical device within the electroporation area;
• Administration of any vaccine within 4 weeks of first dose;
• Administration of any blood product within 3 months of first dose;
• Current or anticipated concomitant immunosuppressive therapy (excluding inhaled, topical skin and/or eye drop-containing corticosteroids, or low-dose methotrexate). Systemic corticosteroids must be discontinued at least 4 weeks prior to first dose;
• Current or anticipated treatment with TNF-α inhibitors such as infliximab, adalimumab, etanercept;
• Active military service personnel;
• Prisoner or subjects who are compulsorily detained (involuntary incarceration) for treatment of either a physical or psychiatric illness;
• Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements or assessment of immunologic endpoints; or
• Any illness or condition that in the opinion of the investigator may affect the safety of the subject or the evaluation of any study endpoint.

In Part II only (Groups 3A and 3B), the current strength of the device will be masked from the study team administering the procedure and participant. All IP assignments will be open label and unmasked.