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To assess the safety and immune response to two experimental vaccines when formulated with QS-21 or QS-21 plus alum. To determine whether the new preparation of QS-21 in polysorbate 80 is less reactogenic than the QS-21 formulation used in AVEG Protocols 016, 016A, and 016B. To examine whether QS-21 is immunologically equivalent to that used in 16B. To determine if QS-21, when given with low doses of antigen, induces measurable HIV-1-specific CTL activity. To evaluate if the QS-21 dose-sparing effect extends to an antigen dose of 0.5 micrograms. To determine if the bivalent vaccine gives responses equivalent to the monovalent product or if a broadening of the HIV-1-specific binding and neutralizing antibody responses occurs. An effective vaccine to prevent HIV-1 infection may need to generate diverse and multifaceted immunologic responses. Required parts of the immune response may include: humoral antibodies, which broadly neutralize non-syncytium-inducing strains of HIV-1; T cell help provided by both CD4 and CD8 positive subsets; and a class I-restricted cytotoxic lymphocyte response. Other effector responses, such as the generation of antibody-dependent cellular cytotoxicity, cytokines, chemokines, or other antiviral factors may also be critical in mounting protective immunity. Given the lack of a surrogate immunologic marker, the most practical approach for possible efficacy trials would be to evaluate a candidate vaccine that elicits as many of these responses as possible. An effective vaccine to prevent HIV-1 infection may need to generate diverse and multifaceted immunologic responses. Required parts of the immune response may include: humoral antibodies, which broadly neutralize non-syncytium-inducing strains of HIV-1; T cell help provided by both CD4 and CD8 positive subsets; and a class I-restricted cytotoxic lymphocyte response. Other effector responses, such as the generation of antibody-dependent cellular cytotoxicity, cytokines, chemokines, or other antiviral factors may also be critical in mounting protective immunity. Given the lack of a surrogate immunologic marker, the most practical approach for possible efficacy trials would be to evaluate a candidate vaccine that elicits as many of these responses as possible. Volunteers in each of 5 groups receive vaccine or placebo by intramuscular injection at Months 0, 1, and 6. All patients receive one of two doses of QS-21 along with vaccine or placebo and some groups receive alum as follows: Group 1: low-dose MN rsgp120/HIV-1 plus QS-21 (13 volunteers). Group 2: high-dose MN rsgp120/HIV-1 plus QS-21 (13 volunteers). Group 3: AIDSVAX B/E (injection contains each of the two vaccine components, HIV-1 MN rgp120 and A244 rgp120/HIV-1) plus QS-21 plus alum (13 volunteers). Group 4: high-dose MN rgp120/HIV-1 plus QS-21 plus alum (13 volunteers). Group 5: placebo plus QS-21 (8 volunteers). Volunteers will be closely monitored after each immunization and followed for a minimum of 12 months after the initial immunization.
Inclusion Criteria Volunteers must have: * Negative ELISA for HIV within 8 weeks prior to immunization. * CD4 count greater than or equal to 400 cells/mm3. * Normal history and physical examination. \[Refer to Laboratory values for additional requirements.\] Exclusion Criteria Co-existing Condition: Volunteers with the following conditions or symptoms are excluded: * Medical or psychiatric conditions or occupational responsibilities which preclude subject compliance with the protocol. * Recent suicidal ideation or psychosis. * Active syphilis. NOTE: If the serology is documented to be a false positive or due to a remote (greater than 6 months) treated infection, the volunteer is eligible. * Active tuberculosis. NOTE: Volunteers with a positive PPD and a normal chest x-ray showing no evidence of TB and not requiring INH therapy are eligible. * Positive for hepatitis B surface antigen. Volunteers with the following prior conditions are excluded: * History of immunodeficiency, chronic illness, or autoimmune disease. * History of cancer unless there has been surgical excision followed by a sufficient observation period to give a reasonable assurance of cure. * History of suicide attempts, recent suicidal ideation, or past or present psychosis. * History of anaphylaxis or other serious adverse reactions to vaccines. * History of serious allergic reaction to any substance requiring hospitalization or emergency medical care (e.g., Stevens-Johnson syndrome, bronchospasm, or hypotension). * History of reaction to thimerosal. Prior Medication: Excluded: * Live attenuated vaccine within 60 days of study. NOTE: Medically indicated subunit or killed vaccines (e.g., influenza, pneumococcal) are not exclusionary, but should be given at least 2 weeks away from HIV immunizations. * Experimental agents within 30 days prior to study. * HIV-1 vaccines or placebo as part of a previous HIV vaccine trial. Prior Treatment: Excluded: * Blood products or immunoglobulin in the past 6 months. * Experimental agents within 30 days prior to study. Risk Behavior: Excluded: * Volunteers with an identifiable higher- or intermediate-risk sexual behavior for HIV infection (i.e., AVEG Risk Groups C or D ). * History of intravenous drug use within 12 months prior to enrollment.