A Study to Evaluate the Safety and Effectiveness of HIV-1 LAI gp120 (an HIV Vaccine) Given With or Without HIV-1 MN rgp120 (Another HIV Vaccine) to HIV-Negative Volunteers

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and effectiveness of giving healthy volunteers a new oral HIV vaccine which has been incorporated into a bacterial cell. This oral vaccine (HIV-1 LAI gp120) will be given with or without a different injected HIV vaccine (HIV-1 MN rgp120). Vaccines are preparations that are introduced into the body to try to prevent infection or create resistance to infection. This study examines a new oral vaccine to see if it can improve the immune system's ability to fight the HIV virus when given alone or with another injected vaccine.

Detailed Description
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Although recent advances have been made in antiviral therapy for AIDS, there is no cure for HIV-1 infection or AIDS, and drug therapy is too expensive for most affected populations. The development of safe, effective vaccines to prevent HIV-1 infection and AIDS worldwide is a global priority. One promising approach in the development of HIV-1 vaccines utilizes live vaccines as vectors to express HIV-1 antigens. The potential advantages of the live vector approach include the ability of live vector recombinants to induce long-lasting humoral and cell-mediated immunity (particularly neutralizing antibody and CD8+ cytotoxic T-cell activity) and the relatively low cost of production. Moreover, live vector recombinant vaccines administered orally might be able to stimulate the production of secretory IgA vaccine-specific antibodies locally at relevant mucosal sites. Part I of this study is conducted as an open-label, dose-escalation trial. The first 5 volunteers (Group A) receive a single oral dose of Salmonella typhi CVD 908-HIV-1 LAI gp 120 (VVG203). If no typhoid fever-like illness is seen in these volunteers during at least 14 days of follow-up, the next 5 patients (Group B) receive a single dose of VVG203. If this higher dose is well-tolerated, Phase II of the study is initiated once all Phase I volunteers have been assessed for safety for at least 21 days. [AS PER AMENDMENT 11/07/97: Groups A and B are expanded to 10 patients each.] Part II of this study is a randomized, placebo-controlled, double-blind trial. Nine volunteers are randomized to each of treatment groups, with oral VVG203 given alone or sequentially with HIV-1 SF-2 rgp 120 in MF59 (SF) given intramuscularly. [AS PER AMENDMENT 11/07/97: Randomization is to VVG 203 alone or sequentially with HIV-1 MN rgp120 in alum (MN).] A total of 3 vaccinations are administered within each 9-person cohort, 1 volunteer serves as a control and receives a sodium bicarbonate buffer rather than VVG203 or a vaccine placebo rather than SF. Group C receives VVG at Month 0 and SF at Months 2 and 6. Group D receives VVG at Months 0, 2, and 6. Group E receives SF at Months 0 and 2 and VVG at Month 6. [AS PER AMENDMENT 11/07/97: MN is given in place of SF in all Groups C, D, and E.]

Official Title
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A Phase I Safety and Immunogenicity Trial of Orally Administered Live Attenuated Recombinant Salmonella Typhi CVD 908 Delta-asd (pW57-asd+) Expressing HIV-1 LAI gp120 (VVG 203) and Parenterally Administered HIV-1 MN rgp120 in Alum in HIV-1-Uninfected Volunteers

Conditions
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HIV Infections, HIV Seronegativity

Intervention / Treatment
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* Biological: Salmonella typhi CVD 908-HIV-1 LAI gp 120 (VVG 203)
* Biological: Aluminum hydroxide
* Biological: MF59
* Biological: rgp120/HIV-1MN


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria You may be eligible for this study if you: Are 18-50 years old. Are HIV-negative. Are healthy and have a normal history and physical exam. Agree to practice abstinence or use of effective birth control for 1 month before and during the study. Exclusion Criteria You will not be eligible for this study if you: Have a history of immune deficiency, chronic illness, or autoimmune disease. Have received immunosuppressive medications, blood products, trial drugs, immunoglobulins, or an HIV or typhoid vaccine. Have a history of severe allergic reactions. Have had prior suicidal attempts or have a psychiatric condition or job commitments which would prevent you from completing the study. Have a history of cancer (unless the cancer has been successfully cured), gallbladder disease, typhoid fever, migraines or other severe headaches, cardiac valve defects, or congenital heart disease. Have active syphilis or tuberculosis. Are allergic to certain medications. Are pregnant or breast-feeding. Have household contact with infants or persons who are pregnant, immunodeficient, or HIV-positive. Are unavailable for 12 months of follow-up. Have hepatitis B. Have a history of injection drug use within 12 months of enrollment or have higher or intermediate risk sexual behavior.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: Salmonella typhi CVD 908-HIV-1 LAI gp 120 (VVG 203)|nan|
|Biological: Aluminum hydroxide|nan|
|Biological: MF59|nan|
|Biological: rgp120/HIV-1MN|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV Envelope Protein gp120, Vaccines, Synthetic, HIV-1, Administration, Oral, AIDS Vaccines, HIV Seronegativity, Recombination, Genetic, Salmonella typhi, HIV Preventive Vaccine