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A Phase I, Multicenter, Randomized, Double-Blind, Placebo-Controlled HIV-1 Vaccine Trial to Evaluate the Safety and Immunogenicity of Low Dose MN rsgp120/HIV-1 (Genentech) in Combination With QS21 Adjuvant or Alum in Healthy Adults

Phase 1
Completed
Conditions
HIV Infections
Registration Number
NCT00000853
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Brief Summary

To expand the safety information regarding MN rsgp 120/HIV-1 formulated with QS21 or alum. To evaluate the immunogenicity of low doses of MN rsgp 120/HIV-1 formulated with QS21 or alum.

Studies to date indicate that there may be a dose-sparing effect with the use of QS21. In animal studies, when QS21 has been employed as an adjuvant, it shifted both the dose response curve and allowed less antigen to elicit equivalent binding antibody titers to the rgp120 protein. There may also be an acceleration in the course of antibody response after both the first and the second immunizations. Although the final titers in response to vaccine given in both alum and QS21 appear similar after 3 doses in humans, this plateau may be reached more readily, and with a lower antigen dose, when using QS21 as an adjuvant. In addition, it has been established that using a lower dose of antigen may elicit an immune response which is characterized by lymphoproliferation and production of TH1-like cytokines such as INF-gamma, interleukin-2, interleukin-4, interleukin-5 and interleukin-10.

Detailed Description

Studies to date indicate that there may be a dose-sparing effect with the use of QS21. In animal studies, when QS21 has been employed as an adjuvant, it shifted both the dose response curve and allowed less antigen to elicit equivalent binding antibody titers to the rgp120 protein. There may also be an acceleration in the course of antibody response after both the first and the second immunizations. Although the final titers in response to vaccine given in both alum and QS21 appear similar after 3 doses in humans, this plateau may be reached more readily, and with a lower antigen dose, when using QS21 as an adjuvant. In addition, it has been established that using a lower dose of antigen may elicit an immune response which is characterized by lymphoproliferation and production of TH1-like cytokines such as INF-gamma, interleukin-2, interleukin-4, interleukin-5 and interleukin-10.

Patients will be recruited and screened and those determined as eligible will be enrolled in the study. Initially, 5 patients will be randomized into each combination of MN rsgp 120/HIV-1 dose and adjuvant, QS21 or alum, along with 2 controls for each adjuvant group. An additional 10 patients will be randomized equally between the QS21 and alum arms to the lowest dose group having 2 or more responders defined as an MN Vital Dye neutralization titer greater than or equal to 10 measured at 2 weeks after the second vaccination. 1 additional control will also be randomized to each adjuvant group. If neither dose has 2 or more responders, no additional patients will be enrolled. Patients will receive their randomly assigned injections at months 0, 1 and 6. Patients will be tested for DTH to MN rsgp 120 at 12 months.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
37
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (3)

UAB AVEG

🇺🇸

Birmingham, Alabama, United States

Univ. of Rochester AVEG

🇺🇸

Rochester, New York, United States

UW - Seattle AVEG

🇺🇸

Seattle, Washington, United States

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