⁃ All participants (vaccinees, household contacts, and intimate contacts) must meet all of the following criteria:

• Age 18 to 49 years for vaccinees. Age 18 to 65 years for household and intimate contacts.

• Negative FDA-approved HIV test.

• Available and willing to participate in follow-up visits and tests for the duration of the study.

• Willing to have samples stored for future research.

⁃ The following inclusion criteria apply to vaccinees and intimate contacts, but not to household contacts:

• In good general health without clinically significant medical history.

• Assessed as low risk for HIV infection by agreeing to discuss HIV infection risks with the study clinicians, agreeing to HIV risk reduction counseling, and agreeing to avoid behavior associated with high risk of HIV exposure through the last required clinic visit in the protocol schedule.

• Negative beta-HCG pregnancy test for females presumed to be of reproductive potential.

• Female vaccinees and male intimate contacts must meet one of the following criteria:

⁃ The female vaccinee has no reproductive potential because of menopause (1 year without menses) or because of a hysterectomy, bilateral oophorectomy, medically-documented ovarian failure, or tubal ligation.

• or

⁃ The female vaccinee and her male intimate contact(s) agree to be heterosexually inactive or consistently practice contraception at least 21 days prior to each vaccination through 21 days following each vaccination. Acceptable methods of contraception include any of

• the following:

⁃ condoms, male or female, with a spermicide.

⁃ diaphragm or cervical cap with spermicide.

⁃ contraceptive pills, Norplant, or Depo-Provera (and is not on any medications that would interfere with the effectiveness of these contraceptive agents).

⁃ male partner has previously undergone a vasectomy for which there is documentation.

⁃ intrauterine device.

• Male vaccinees and female intimate contacts must agree to consistently practice abstinence or effective birth control (described above) and for 21 days following each vaccination.

⁃ The following inclusion criteria apply only to vaccinees and not to household or intimate contacts:

• Willing to receive HIV test results and abide by NIH guidelines for partner notification of positive HIV results.

• Physical examination and laboratory results without clinically significant findings within the 8 weeks prior to enrollment.

• Willing to avoid other investigational and/or HIV vaccinations, other than the study agent, from screening through the end-of-study visit.

• Safety laboratory criteria within 8 weeks prior to enrollment:

‣ Hematologic:

• White blood cell count and lymphocyte count within 25% of both the lower limit and upper limit of normal for the NIH CC (ranges: 2.985-12.55 K/uL for white blood cells and 0.885 - 4.675 K/uL for lymphocytes).

∙ Platelet count of least 150,000/mm\^3.

∙ Hemoglobin count within 10% of both the lower limit and upper limit of normal for the NIH CC (ranges: Females 10.08 - 17.27 g/dL, Males 12.33 -19.25 g/dL)

⁃ Renal: Blood urea nitrogen (BUN) \<23 mg/dL; creatinine within normal limits for the NIH CC (females: 0.51-0.95 mg/dL; males: 0.67-1.17 mg/dL).

⁃ Hepatic: Serum direct bilirubin within normal limits for the NIH CC (0.0 to 0.3 mg/dL).

⁃ Metabolic: Alanine aminotransferase (ALT) \<2 times upper limit of normal range (females: \<66 U/L; males: \<82 U/L).

• 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 Arm B.)

• Willing to follow precautions for preventing the spread of adenovirus in the community.

• Males must agree not to donate sperm for 21 days following each study vaccination.