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To evaluate the safety of HIV-1 gp120 C4-V3 hybrid polyvalent peptide immunogen (C4-V3 peptides) formulated in mineral oil containing mannose mono-oleate (IFA) in HIV-1 uninfected volunteers. To evaluate the humoral and cellular immune responses to the C4-V3 peptides as measured by the induction of 1 or more of the following: neutralizing antibodies to HIV-1 MN and RF, cross-neutralizing antibodies to primary isolates of HIV-1, HIV-1 antigen-specific lymphoproliferation, CD8+ and CD4+ cytotoxic T lymphocyte (CTL) activity specific for HIV-1 gp120 or V3 peptides corresponding to the vaccine strains of HIV-1, induction of HLA-B7 and HLA-A2 restricted CD8+CTLs, and induction of HIV-specific DTH responses. The test immunogen (C4-V3 peptides) is constructed from 4 sequences of the HIV-1 V3 gp120 loop shared by approximately 80% of North American HIV-1 strains. Because of the critical role that this region plays in generating anti-HIV sequences, it is hypothesized that the test immunogen (C4-V3 peptides) will be capable of inducing a broad range of cross-reactive neutralizing antibodies in the majority of recipients. The test immunogen (C4-V3 peptides) is constructed from 4 sequences of the HIV-1 V3 gp120 loop shared by approximately 80% of North American HIV-1 strains. Because of the critical role that this region plays in generating anti-HIV sequences, it is hypothesized that the test immunogen (C4-V3 peptides) will be capable of inducing a broad range of cross-reactive neutralizing antibodies in the majority of recipients. Twenty-eight volunteers are randomized to receive two 0.5 ml injections of C4-43 peptides in IFA or placebo (IFA alone) administered intramuscularly at 0, 1, 6, and 12 months. At least 50% of all volunteers (6 per Groups I and II; 2, Group III) must be HLA-B7 phenotype.
Inclusion Criteria Volunteers must have: * Negative ELISA for HIV within 8 weeks of immunization. * Normal history and physical examination. * Normal chest x-ray within 4 weeks prior to initial immunization. * Low-risk sexual behavior as defined by AVEG. Exclusion Criteria Co-existing Condition: Volunteers with the following conditions are excluded: * Medical or psychiatric condition that precludes compliance with the protocol, including recent suicidal ideation or present psychosis. * Occupational responsibilities which preclude compliance with the protocol. * Active syphilis (if the serology is documented to be a false positive or due to a remote \[more than 6 months\] treated infection, the volunteer is eligible). * Active tuberculosis (volunteers with a positive purified protein derivative and a normal chest x-ray showing no evidence of TB and not requiring isoniazid therapy are eligible). * Positivity for hepatitis B surface antigen. Volunteers with the following prior conditions are excluded: * History of immunodeficiency, chronic illness, malignancy, or autoimmune disease. NOTE: Individuals with a history of cancer are excluded unless there has been surgical excision followed by a sufficient observation period to give a reasonable assurance of cure. * History of suicide attempts or past psychosis. * History of anaphylaxis or other serious adverse reactions to vaccines. * History of serious allergic reaction to any substance, requiring hospitalization or emergent medical care (e.g., Stevens-Johnson syndrome, bronchospasm, or hypotension). * History of lung disease. Prior Medication: Excluded: * Live attenuated vaccines 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, received in a previous HIV vaccine trial. * Immunosuppressive medications. Prior Treatment: Excluded: * Receipt of blood products or immunoglobulin in the past 6 months. Risk Behavior: Excluded: * Alcohol intake greater than or equal to the equivalent of 1 oz of 100 proof per day (4 oz. glass of wine or 12 oz. of beer per day). * Identifiable higher-risk behavior for HIV infection as determined by screening questions designed to identify risk factors for HIV infection; specific exclusions include a history of injection drug use within the last 12 months prior to enrollment and higher- or immediate-risk sexual behavior as defined by the AVEG (i.e., meeting the criteria for AVEG Risk Groups C and D).