Safety of and Immune Response to a Prime-Boost Vaccine Regimen in HIV-Uninfected Vaccine-Naive Adults

Inclusion Criteria: * Access to a participating HIV Vaccine Trials Network (HVTN) clinical research center and willing to be followed for the planned duration of the study * Ability and willingness to provide informed consent * Assessment of understanding: completion of a questionnaire prior to first vaccination; demonstration of understanding for all questionnaire items answered incorrectly * Willingness to receive HIV test results * Good general health as shown by medical history, physical exam, and screening laboratory tests * Certain specified laboratory values. More information on this criterion can be found in the study protocol. * If pregnancy is possible, must agree to use contraception from at least 21 days prior to enrollment through the last protocol visit for sexual activity that could lead to pregnancy. More information on this criterion can be found in the study protocol. * Willingness to discuss HIV infection risks, amenable to HIV risk reduction counseling, committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit, and willing to continue annual follow-up contact after the last required protocol clinic visit for a total of 5 years following enrollment * Assessed by clinic staff as being at "low risk" of HIV infection on the basis of sexual behaviors within the 12 months prior to enrollment. More information on this criterion can be found in the study protocol. Exclusion Criteria: * HIV vaccine(s) or other experimental vaccines, received in a prior HIV vaccine trial. More information on this criterion can be found in the study protocol. * Receipt of smallpox vaccination * Excessive alcohol use, frequent binge drinking, chronic marijuana abuse, or use of any other illicit drugs, such as cocaine or methamphetamine, within the past 12 months * History of newly acquired or newly diagnosed syphilis; history of newly acquired gonorrhea, nongonococcal urethritis, herpes simplex virus type 2 (HSV2), chlamydia, pelvic inflammatory disease (PID), trichomonas, mucopurulent cervicitis,epididymitis, proctitis, lymphogranuloma venereum, chancroid, or hepatitis B within the past 12 months * Immunosuppressive medication received within 168 days before first vaccination. Certain medications are excluded from this criterion; more information can be found in the study protocol. * 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 * Influenza vaccine or any vaccines that are not live attenuated and were received within 14 days prior to first vaccination or that are scheduled within 14 days after injection * Allergy treatment with antigen injections within 30 days before first vaccination or scheduled within 14 days after injection * Intent to participate in another study of an investigational research agent during the planned duration of this study * Current anti-tuberculosis (TB) prophylaxis or therapy * Clinically significant medical condition. More information on this criterion can be found in the study protocol. * Any medical, psychiatric, or social condition or occupational or other responsibility that in the opinion of the investigator might interfere with the study protocol * Serious adverse reactions to vaccines. More information on this criterion can be found in the study protocol. * Allergy to eggs and/or egg products * History of or known active cardiac disease. More information on this criterion can be found in the study protocol. * Participants who have two or more of the following cardiac risk factors: (1) participant report of history of elevated blood cholesterol defined as fasting low-density lipoprotein (LDL) greater than 160 mg/dL; (2) first degree relative (e.g., mother, father, sister, or brother) who had coronary artery disease before the age of 50 years; (3) current smoker; or (4) body mass index greater than or equal to 35. * Electrocardiogram (ECG) with clinically significant findings. More information on this criterion can be found in the study protocol. * Autoimmune disease * Immunodeficiency * Asthma other than mild, well-controlled asthma. More information on this criterion can be found in the study protocol. * Diabetes mellitus, type 1 or type 2, including cases controlled with diet alone. Those with a history of isolated gestational diabetes are not excluded. * 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. More information on this criterion can be found in the study protocol. * Body mass index greater than or equal to 40 * Bleeding disorder diagnosed by a doctor * Malignancy. Participants with surgical excisions and subsequent observation periods, that in the investigator's estimation have a reasonable assurance of sustained cure or are unlikely to recur during the period of study, are not excluded. * Seizure disorder, unless the participant has not required medication or had a seizure within the last 3 years. * Asplenia * Pregnant or breastfeeding