The purpose of this study is to find out whether three different anti-HIV vaccines are safe and whether they help prevent HIV infection. These vaccines are called vCP205, vCP1433, and vCP1452. Some patients also receive another anti-HIV vaccine, gp160. The vaccines are made up of small pieces of HIV, which help the body learn to recognize and destroy HIV. You cannot get HIV from these vaccines.

There are two different ways a vaccine can protect the body from infection. First, a vaccine may help the immune system make antibodies, which are proteins that recognize invading viruses or bacteria. Second, a vaccine may help the body make immune cells that destroy infected cells. The second type of vaccine is more powerful against HIV. In this study, doctors will see whether vCP205, vCP1433, vCP1452, and gp160 are good vaccines by seeing whether they help the body make immune cells.

Previous studies in humans have shown that immunization with certain vaccine combinations (that is, ALVAC-HIV construct and an envelope subunit vaccine) can elicit CTL activity, antibody-dependent cellular toxicity (ADCC), neutralizing antibodies, and other antibody responses more often and at higher levels than either vaccine alone. This study examines improved vaccine candidates that can elicit broader, longer-lasting CTL activity in the majority of vaccine recipients.

Volunteers are randomized to one of four groups. Group I receives vCP205. Group II receives vCP1433. Group III receives vCP1452. Group IV receives an ALVAC rabies vaccine, as a control. Immunizations are administered at Months 0, 1, 3, and 6. At Months 3 and 6, patients in Groups I, II, and III also receive gp160 MN/LAI-2, the subunit boost vaccine. Group IV receives another placebo vaccine. Participants have regular clinic visits and blood is drawn to determine humoral and cellular immune responses to the vaccines. [AS PER AMENDMENT 10/23/98: A cell-mediated immunity substudy has been added at selected institutions following the fourth vaccination at 6 months; this study will assess the newer assays of CD8+ T cells and the kinetic response following immunization. The 6-month immunization may be rescheduled by up to 14 days to accommodate clinical, laboratory, or volunteer scheduling issues.] [AS PER AMENDMENT 6/17/99: Three study arms are added. Group V receives vCP1452 at Months 0,1,3, and 6. Group VI receives vCP205 at Months 0,1,3, and 6. Group VII receives placebo at Months 0,1,3, and 6. Patients in Groups V, VI, and VII do not receive the subunit boost, gp160 MN/LAI-2. Consenting volunteers enrolled in the three new groups at Johns Hopkins University undergo PET scanning as part of an ancillary study.]

Inclusion Criteria

You may be eligible for this study if you:

• Are 18-60 years old.
• Are HIV-negative and are in good health.
• Have a CD4 count of at least 400 cells/mm3.
• Test negative for hepatitis B.
• Agree to use effective methods of birth control for 1 month before and during the study.

Exclusion Criteria

You will not be eligible for this study if you:

• Are at high risk for being infected with HIV (risky sex behavior or injection drug use within 12 months prior to study entry).
• Have a serious medical condition, or if you have had chronic sickness, diseases of the immune system, or cancer that was not cured through surgery.
• Have a serious psychiatric condition or if you have been suicidal.
• Have a work commitment that would keep you from completing the study.
• Have syphilis or tuberculosis.
• Are allergic to eggs, neomycin, vaccines, or have ever had severe allergic reactions.
• Have taken certain medicines, including medicines that affect the immune system or experimental medicines.
• Have participated in another HIV vaccine trial.
• Have received any vaccines within 2 weeks of study entry.
• Have received a blood transfusion within 6 months prior to study entry.
• Are pregnant or breast-feeding.