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
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): rgp120/HIV-1MN
Intervention type(s): Biological
Masking: Double
Primary purpose: Prevention
Keywords: Vaccines, Synthetic; HIV-1; HIV Envelope Protein gp120; AIDS Vaccines; HIV Seronegativity; HIV Preventive Vaccine