A Study to Assess the Safety and Immune Response to Env-C DNA and Protein Vaccines in Kenya

Inclusion Criteria: * Healthy, male and female participant aged 18 to 40 years and available for 26 months. * Must be at low risk for HIV infection per investigator assessment and using the study risk assessment tool. * Must be able to understand and complete the informed consent process. * Must be capable of reading English or Kiswahili. * Must agree to a home visit. * Must complete a Test of Understanding (TOU) before enrollment. Must answer 9 out of 10 questions correctly with a maximum of three attempts. * Must be in good general health without a clinically significant medical history. * HIV-uninfected per diagnostic algorithm within 45 days of enrollment. * Laboratory values: * Hemoglobin * 12.5-18.1 g/dL men * 11.0-16.1 g/dL women * White Cell Count * 2.7-7.7 x 10³ cells/µL men * 3.0-9.1 x 10³ cells/µL women * Platelets: * 125-370 10³ cells/µL men * 125-444 10³ cells/µL women * ALT and AST: ≤1.25 institutional upper limit of the reference range * Creatinine: ≤1.25 institutional upper limit of the reference range * Urinalysis: (dipstick) for blood and protein less than 1+ and negative glucose Female-Specific Criteria * Negative urine pregnancy test for women at screening, the day of each vaccination, and before any invasive procedure. * Already using and commits to continued use of an adequate birth control method for 45 days before to the first vaccination/placebo vaccination, and for at least 90 days after the final vaccine/placebo vaccination. Adequate birth control is defined as follows: Contraceptive medications delivered orally, intramuscularly, vaginally, or implanted, underneath the skin, surgical methods (hysterectomy or bilateral tubal ligation), condoms with spermicide, diaphragms, intrauterine device (IUD), vasectomy in a monogamous partner, or abstinence. Lymph Node Biopsy Inclusion Criteria * Body mass index (BMI) \<35 * Platelets \>150,000 * International normalized ration (INR) \<1.2 * Verbal report of no NSAIDS/aspirin for 7 days prior. * Negative pregnancy test for participants born female. Exclusion Criteria: A history of: * Three or more sexual partners in the previous 24 weeks. * Commercial sex work. * Non-adherence to condom use in the absence of a long-term monogamous relationship. * Intravenous drug use in the previous year. * A sexually transmitted infection in the previous 24 weeks. * Asplenia: any condition resulting in the absence of a functional spleen. * Bleeding disorder diagnosed by a medical doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions). * Breastfeeding or pregnant (positive pregnancy test) women or planning to become pregnant during the window between study enrollment and three months after the last vaccination visit. * Any past, ongoing, or in remission history of treated or untreated autoimmune disease. * Has known active Hepatitis B virus infection (or positive HBsAg). * Has known active Hepatitis C infection. * History of anaphylaxis or other serious adverse reaction to vaccines or allergies or reactions likely to be exacerbated by any component of the vaccine and placebo, including antibiotics or excipients. * Absolute Neutrophil Count (ANC) \<1.0 x 10³ cells/µL. * Participant has received any of the following substances: * Chronic use of therapies that may modify immune response, such as intravenous (IV) immune globulin and systemic corticosteroids (in doses of \>20 mg/day prednisone equivalent for periods exceeding 10 days). * The following exceptions are permitted and will not exclude study participation: * Use of corticosteroid nasal spray for rhinitis; * Topical corticosteroids for an acute uncomplicated dermatitis; or * A short course (10 days or less, or a single injection) of corticosteroid for a non-chronic condition (based on investigator clinical judgment) at least 2 weeks before enrollment. * Blood products within 120 days before HIV screening. * Immunoglobulins within 30 days before HIV screening. * Any experimental vaccine containing an adjuvant other than aluminum of an adjuvant not approved by the FDA or European Medicines Agency (EMA) as part of a licensed vaccine. * CERVARIX vaccine against HPV (containing AS04) * Receipt of any investigational HIV vaccine, investigational research agents or vaccine within 30 days before enrollment. * Anti-tuberculosis prophylaxis or therapy during the past 90 days before enrollment. * Any psychiatric, social condition, occupational reason, or other responsibility that, in the judgment of the investigator, is a contraindication to protocol compliance or impairs a participant's ability to give informed consent. * Major psychiatric illness and or substance abuse problems during the past 12 months that, in the opinion of the investigator, would preclude participation. * History of atopy or significant skin conditions. * Study site employees who are involved in the protocol and or may have direct access to the study-related area. Lymph Node Biopsy Exclusion Criteria * History of keloid formation. * History of an inguinal hernia, inguinal canal cryptorchidism, varicocele, hydrocele. * History of inguinal excisional lymph node biopsy. Final evaluation of eligibility is based on the medical judgment of the investigator. The Protocol Safety Review Team will also remain available to the investigator for consultation if desired.