Study of Safety and Immunogenicity of HIV Vaccines in Healthy Volunteers

* INCLUSION CRITERIA: All participants (vaccinees, household contacts, and intimate contacts) must meet all of the following criteria: 1. Age 18 to 49 years for vaccinees. Age 18 to 65 years for household and intimate contacts. 2. Negative FDA-approved HIV test. 3. Able to provide proof of identity to the acceptance of the Principal Investigator or designee during enrollment. 4. Available and willing to participate in follow-up visits and tests for the duration of the study. 5. Willing to have samples stored for future research. The following inclusion criteria apply to vaccinees and intimate contacts, but not to household contacts: 1. In good general health without clinically significant medical history. 2. Willing to discuss HIV infection risks with the study clinicians, assessed as low risk for HIV infection, amenable to HIV risk reduction counseling, and committed to maintaining behavior consistent with low risk of HIV exposure through the last required clinic visit in the protocol schedule. 3. Negative Beta-HCG pregnancy test for females presumed to be of reproductive potential. 4. A female must meet one of the following criteria: 1. No reproductive potential because of menopause (one year without menses) or because of a hysterectomy, bilateral oophorectomy, or tubal ligation. OR 2. Participant agrees to be heterosexually inactive or consistently practice contraception at least 21 days prior to and 28 days following each vaccination. Acceptable methods of contraception include the following: * condoms, male or female, with a spermicide. * diaphragm or cervical cap with spermicide. * contraceptive pills, Norplant, or Depo-Provera. * male partner has previously undergone a vasectomy for which there is documentation. * intrauterine device. 5. Male participants must agree to practice abstinence or effective birth control for at least 21 days prior to and 28 days following each vaccination. The following inclusion criteria apply only to vaccinees and not to household or intimate contacts: 1. Willing to receive HIV test results and abide by NIH guidelines for partner notification of positive HIV results. 2. Physical examination and laboratory results without clinically significant findings within the 8 weeks prior to enrollment. 3. Willing to avoid vaccination other than the study agent for 30 days prior to and 30 days after administration of the Ad4-HIV vaccine. 4. Safety Laboratory Criteria within 8 weeks prior to enrollment: Hematopoietic: -White blood cell count and Lymphocyte count +/- 25% of normal limits for the NIH Clinical Center * Platelet count of least 100,000/mm(3) * Hemoglobin \>11.2 g/dL for females and \>13.0 g/dL for males. Renal: BUN \<23 mg/dL; creatinine within normal limits for the NIH Clinical Center Hepatic: Serum total bilirubin less than or equal to 2 mg/dL Metabolic: ALT \<2 times upper limit of normal range Endocrine: Serum glucose within normal range 5. Additional Laboratory Criteria: Immunologic: No history of hypogammaglobulinemia Serologic: Ad4 neutralizing antibody 80% inhibitory dilution \<1:100 (This criterion does not apply to participants in Arms C and D.) The following inclusion criterion applies only to intranasal vaccinees and not to capsule vaccine recipients or household or intimate contacts: 1\. Willing to either: 1. be hospitalized at the Clinical Center under respiratory precautions for up to 7 days or longer if medically indicated (required for those with household contact(s) until they show seroconversion); or 2. follow precautions for preventing the spread of adenovirus in the community. EXCLUSION CRITERIA: A participant (vaccinees, household contacts, and intimate contacts) will be excluded if they have the following: 1\. Any condition that, in the investigator s judgement, places the subject at undue risk by participating in the study. The following exclusion criterion applies to vaccinees and intimate contacts, but not to household contacts: 1. History of any prior disease or therapy which would affect immune or pulmonary function. 2. Prior malignancy, except curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix. 3. History of radiation therapy or cytotoxic/cancer chemotherapy. 4. History of diabetes mellitus. 5. Immunodeficiency or autoimmune disease. 6. Acute infection or a recent (within 6 months) history of chronic infection suggestive of immunodeficiency. 7. Taking any medication which may affect immune function, except participants may be taking low doses of nonprescription strength NSAIDS (including e.g. ibuprofen or aspirin) or acetaminophen. 8. Chronic respiratory disorders including asthma, emphysema, interstitial lung disease, pulmonary hypertension, recurrent pneumonia, or recent or ongoing respiratory tract infection. If a respiratory disorder is transient, defer immunization but do not exclude the participant. 9. Active Hepatitis B or C infection (i.e. Hepatitis B or C positive serology with the presence of virus antigen or DNA. Ongoing viral replication will be confirmed by a Hepatitis B antigen or Hepatitis C viral load). 10. Female of child-bearing potential who is breast-feeding or planning pregnancy during the 28 days following vaccination. The following exclusion criteria apply only to vaccinees and not to household or intimate contacts: 1. Any medical, psychiatric, or social condition, or occupational or other responsibility that, in the judgment of the investigator, would interfere with or serve as a contraindication to receipt of live virus vaccine, protocol adherence, or a participant s ability to give informed consent. 2. Psychiatric condition that precludes compliance with the protocol; past or present psychoses; past or present bipolar disorder requiring therapy that has not been well controlled on medication for the past two years; disorder requiring lithium; or suicidal ideation occurring within five years prior to enrollment. 3. Participants that live in the same house or apartment with any of the following will be excluded: 1. An individual under 18 years of age. 2. An elderly individual (\>65 years of age). 3. An immunocompromised or immunosuppressed individual. 4. An individual with chronic respiratory disease. 5. A woman who is currently pregnant or planning a pregnancy during the period of immunization. 4. Healthcare worker who has direct contact with immunodeficient, unstable patients, or pediatric patients. 5. Participants caring for children \<18 years of age. 6. Receipt of any of the following: * Antiviral medications within 30 days prior to vaccination. * Blood products within 120 days prior to HIV screening. * Immunoglobulin within 60 days prior to HIV screening. * Investigational research drugs or any other investigational agent that in the judgement of the Principal Investigator might interact with the study vaccine within 30 days prior to initial study vaccine administration. * Allergy treatment with antigen injections within 30 days of study vaccine administration. 7. History of Guillain-Barr(SqrRoot)(Copyright) syndrome. 8. Indeterminate HIV Western Blot test. 9. Prior receipt of an Ad5-based vaccine.