OUTLINE OF PROTOCOL 016B

Subjects: Healthy, HIV-1 uninfected adult volunteers with lower-risk behavior for HIV-1 infection, who meet the eligibility criteria.

Schema:

Immunizations Scheduled at 0, 1, and 6 Months
Dose of
MN rsgp120/HIV-1	100 µg QS21 (Number of subjects)*	Alum (Number of Subjects)*
30 µg	5	5
3 µg	10	10
0 µg	3	3

* Initially, 5 volunteers per treatment arm enrolled at 30 µg dose and 3 µg dose, and 2 volunteers were enrolled in each control arm. The lower dose group with neutralizing antibody responses after two vaccinations (the 3 µg group) was increased to a total of 10 volunteers per treatment arm, and the control group was increased to 3 volunteers in each arm. Total of 37 volunteers enrolled.

Product Description: CHO cell-derived HIV-1 MN rsgp120 in combination with QS21 or alum [Genentech]

Time Period: 18 months; first volunteer enrolled on 11/20/96 and the last on 07/24/97.

Clinical Sites: University of Rochester, Saint Louis University, University of Alabama at Birmingham, University of Washington

Study Chairs: Thomas Evans, University of Rochester and Julie McElrath, University of Washington

INCLUSION CRITERIA

Standard inclusion criteria.

EXCLUSION CRITERIA

Standard exclusion criteria, in addition to:

• History of reaction to thimerosal

STUDY GOALS

• The goal of this study is to extend the evaluation of safety and immunogenicity of low dose MN rsgp120/HIV in combination with QS21, as compared to combination with alum
• To evaluate the safety of a low dose of MN rsgp120/HIV-1 in combination with QS21 or alum
• To evaluate the immunogenicity of a low dose of MN rsgp120/HIV-1 in combination with QS21 or alum
• This amendment will address the following issues that cannot be answered by the current ongoing studies:
  • Clarify whether the use of QS21 shifts the dose response curve so that a lesser amount of antigen can be used with QS21 compared to alum
  • Assess whether the kinetics of antibody response with QS21 are more rapid and superior to that of the same antigen given in alum
  • Assess whether the use of QS21 and low dose antigen leads to a more vigorous TH1-like response, as analyzed by cytokine profile, antibody isotyping and DTH skin testing.