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To evaluate the safety of a fixed antigen dose with an increasing dose of adjuvant (MTP-PE/MF59, a substance to enhance the immune response to vaccine) in volunteers. To evaluate local and systemic reactions (Part A). To determine the safety and immunogenicity of Env 2-3 in combination with MTP-PE/MF59 in volunteers (Part B). The vaccine Env 2-3 is created from one of the viral proteins that make up HIV called envelope glycoprotein gp120. A problem with many immunogens, including candidate HIV vaccines, is that they may evoke relatively weak immune responses, particularly in humans and in nonhuman primates. Thus, there is considerable interest in the development of "adjuvants" (substances that augment immune responses to vaccines). MTP-PE/MF59 is an adjuvant that appears to be particularly promising, and is selected for the studies with this HIV vaccine candidate. The vaccine Env 2-3 is created from one of the viral proteins that make up HIV called envelope glycoprotein gp120. A problem with many immunogens, including candidate HIV vaccines, is that they may evoke relatively weak immune responses, particularly in humans and in nonhuman primates. Thus, there is considerable interest in the development of "adjuvants" (substances that augment immune responses to vaccines). MTP-PE/MF59 is an adjuvant that appears to be particularly promising, and is selected for the studies with this HIV vaccine candidate. This study is being conducted in two parts: Part A examines the safety of the adjuvant MTP-PE/MF59 alone; Part B examines the safety and immunogenicity of Env 2-3 in combination with MTP-PE/MF59. In Part A, three volunteers receive MTP-PE/MF59, and one volunteer receives emulsion alone at each dose level. Initiation of each dose level is separated by at least 72 hours. Doses of adjuvant emulsion are administered at day 0 and day 30 for the highest tolerated dose. If significant reactions are encountered, additional subjects may be studied at lower doses. In Part B, six doses of MTP-PE adjuvant (0, 5, 10, 25, 50, or 100 mcg) in the MF59 emulsion are studied. Six volunteers receive Env 2-3/MTP-PE/MF59 and two receive MTP-PE/MF59 alone at each dose level. There is a minimum 1-week interval between dose escalations. Per amendment, volunteers may receive an additional dose of Env 2-3 or placebo in MF59 emulsion only, administered 12-18 months post initial inoculation.
Inclusion Criteria Volunteers are: * Normal, healthy adults (by history and physical examination) who fully comprehend the purpose and details of the study. Part A: * Available for 60 days. Part B: * Available for 1 year of follow-up. Exclusion Criteria Co-existing Condition: Volunteers with the following conditions or symptoms are excluded: Part B: * Positive syphilis serology (such as VDRL) unless positive test is due to a documented clinical event that occurred and was treated 5 or more years prior to enrollment. Circulating hepatitis B antigenemia. - Volunteers with the following are excluded: * History of immunodeficiency, chronic illness, autoimmune disease. * Evidence of depression or under treatment for psychiatric problems during the past year. Prior Medication: Excluded: * Immunosuppressive medications. Prior Treatment: Excluded: Part B: * Blood transfusion or cryoprecipitates within the past 6 months. Risk Behavior: Excluded: Part B: Identifiable high-risk behavior for HIV infection, including: * history of intravenous drug use; syphilis, gonorrhea, or any other sexually transmitted diseases (including chlamydia or pelvic inflammatory disease) in the last 6 months; more than two sexual partners, or sexual contact with a high-risk partner, in the preceding 6 months.