Phase 1 Safety Study of Two Experimental HIV Vaccines

* INCLUSION CRITERIA: A participant must meet all of the following criteria: 1. 18 to 50 years old. 2. Available for clinical follow-up through Week 24 of the study for subjects in Part I: available for clinical follow-up through Week 52 for subjects in Part II and committed to 4 years of annual follow-up contact after Week 52 if in Part II of the study. 3. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process. 4. Complete an Assessment of Understanding (that includes understanding of Step Study results) prior to enrollment and verbalize understanding of all questions answered incorrectly. 5. Able and willing to complete the informed consent process. 6. Willing to receive HIV test results and willing to abide by NIH guidelines for partner notification of positive HIV results. 7. Willing to donate blood for sample storage to be used for future research. 8. Willing 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 and assessed by the clinic staff as being at low risk of HIV infection on the basis of behaviors in the 12 months prior to enrollment as follows: Sexually abstinent OR Had two or fewer mutually monogamous relationships with partners believed to be HIV-uninfected and who did not use injection drugs, crack cocaine or methamphetamine OR Had three or fewer partners believed to be HIV-uninfected and who did not use injection drugs, crack cocaine or methamphetamine and with whom he/she regularly used condoms for vaginal or anal intercourse. 9. In good general health without clinically significant medical history. 10. Physical examination and laboratory results without clinically significant findings within the 56 days prior to enrollment. Laboratory Criteria within 56 days prior to enrollment: 11. Hemoglobin greater than or equal to 11.5 g/dL for women; greater than or equal to 13.5 g/dL for men. 12. White blood cells (WBC) equals 3,300-12,000 cells/mm(3). 13. Differential either within institutional normal range or accompanied by site physician approval. 14. Total lymphocyte count greater than or equal to 800 cells/mm(3). 15. Platelets equal to 125,000 550,000/mm(3). 16. Alanine aminotransferase (ALT) less than or equal to 1.25 times the upper limit of normal. 17. Serum creatinine less than or equal to upper limit of normal (i.e., less than or equal to 1.3 mg/dL for females; less than or equal to 1.4 mg/dL for males). 18. Normal urinalysis defined as negative glucose, negative or trace protein, and no clinically significant blood in the urine. 19. Negative FDA-approved HIV blood test. 20. Negative hepatitis B surface antigen (HBsAg). 21. Negative anti-hepatitis C virus (HCV) antibody and negative HCV PCR. Laboratory Criteria within 84 days prior to enrollment: 22. Seronegative for Ad35 antibody if enrolled in Part I after the Version 2.0 amendment and seronegative for both Ad5 and Ad35 antibody if in Part II. Female-Specific Criteria: 23. Negative beta-human chorionic gonadotropin pregnancy test (urine or serum) on day of enrollment for women presumed to be of reproductive potential. 24. A female participant must meet any of the following criteria: No reproductive potential because of menopause \[one year without menses\] or because of a hysterectomy, bilateral oophorectomy, or tubal ligation, or Participant agrees to be heterosexually inactive at least 21 days prior to enrollment and through Week 12 of the study for subjects in Part I and through Week 24 of the study for subjects in Part II, or Participant agrees to consistently practice contraception at least 21 days prior to enrollment and through Week 12 of the study for subjects in Part I or through Week 24 of the study for subjects in Part II by one of the following methods: * condoms, male or female, with or without a spermicide * diaphragm or cervical cap with spermicide * intrauterine device * contraceptive pills or patch, Depo-Provera or other FDA-approved contraceptive method * male partner has previously undergone a vasectomy. EXCLUSION CRITERIA: A volunteer will be excluded if one or more of the following conditions apply: Women: 1. Woman who is breast-feeding or planning to become pregnant during the 12 weeks of study participation for subjects in Part I and 24 weeks of study participation for subjects in Part II. Volunteer has received any of the following substances: 2. HIV vaccine in a prior clinical trial. 3. Immunosuppressive medications, cytotoxic medications, inhaled corticosteroids, or long-acting beta-agonists within the past three months. \[With the exceptions that use of corticosteroid nasal spray for rhinitis; topical corticosteroids for an acute uncomplicated dermatitis; short-acting beta-agonists in controlled asthmatics; or a short course (10 days or less) of corticosteroids for a non-chronic condition at least 2 weeks prior to enrollment in this study will not exclude study participation.\] 4. Blood products within 120 days prior to HIV screening. 5. Immunoglobulin within 60 days prior to HIV screening. 6. Investigational research agents within 30 days prior to initial study vaccine administration. 7. Live attenuated vaccines within 30 days prior to initial study vaccine administration. 8. Medically indicated subunit or killed vaccines, e.g. influenza, pneumococcal, or allergy treatment with antigen injections, within 14 days of study vaccine administration. 9. Current anti-tuberculosis prophylaxis or therapy. Volunteer has a history of any of the following clinically significant conditions: 10. Serious adverse reactions to vaccines such as anaphylaxis, urticaria (hives), respiratory difficulty, angioedema, or abdominal pain. 11. Idiopathic urticaria within the past 2 years. 12. Autoimmune disease or immunodeficiency. 13. Asthma that is unstable or required emergent care, urgent care, hospitalization or intubation during the past two years or that requires the use of oral or intravenous corticosteroids. 14. Diabetes mellitus (type I or II), with the exception of gestational diabetes. 15. History of thyroidectomy or thyroid disease that required medication within the past 12 months. 16. A history of hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema. 17. Hypertension that is not well controlled by medication or blood pressure that is more than 145/95 at enrollment. 18. Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws. 19. Within 12 months prior to enrollment: newly-acquired syphilis, gonorrhea, non-gonococcal urethritis, herpes simplex virus type 2 (HSV2), chlamydia, pelvic inflammatory disease (PID), trichomonas, mucopurulent cervicitis, epidiymitis, proctitis, lymphogranuloma venereum, chancroid, or hepatitis B. 20. Malignancy that is active or treated malignancy for which there is not reasonable assurance of sustained cure or malignancy that is likely to recur during the period of the study. 21. Seizure disorder other than: 1) febrile seizures under the age of two, 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) a singular seizure not requiring treatment within the last 3 years. 22. Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen. 23. Psychiatric condition that precludes compliance with the protocol; past or present psychoses; past or present bipolar disorder; disorder requiring lithium; or within five years prior to enrollment, history of a suicide plan or attempt. 24. Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer s ability to give informed consent. 25. BMI greater than or equal to 40; OR BMI greater than or equal to 35 AND with one 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 or quit smoking within 28 days of enrollment * Untreated or poorly controlled hyperlipidemia 26. Within the 12 months prior to enrollment, one or more of the following: * excessive daily alcohol use * frequent binge drinking * chronic marijuana abuse * any other illicit drug use