In this study we propose to continue to develop an anti-idiotype (anti-id) -based strategy for eliciting and/or boosting broadly neutralizing antibodies against HIV. The principle of this approach is based on clonotypic stimulation which utilizes anti-id as surrogate for antigen in an attempt to stimulate specific elements of the B cell repertoire in humans. In phase I of this study, one anti-id Mab (3C9) was identified which induced broadly neutralizing anti-gp12O antibodies in immunonaive monkeys. Our studies will be extended to identify the utility of 3C9 to boosting titers of broadly neutralizing anti-gp12O antibodies.
This aim will be achieved by determining the immunogenicity of 3C9 when tested in HIV-infected individuals and gp120 immune monkeys. In parallel, our efforts will continue to develop new anti-id Mabs which may be superior to 3C9 with respect to their potential as both prophylactic and therapeutic vaccines. We will generate anti-id Mabs which interact with the most prevalent, broadly neutralizing antibodies in the sera of HIV-infected individuals and vaccinated volunteers. These anti-id Mabs will be tested to determine whether they are capable of inducing and boosting the anti-gp12O titer in naive and gp12O primed cynomolgus monkeys. By comparing these results with that of 3C9, we will define new anti-id Mabs for clinical studies. In practice, the anti-id Mabs could be used as a therapy for HIV+ individuals and a prophylactic vaccine when combined with gp12O immunizations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
5R44AI031310-03
Application #
3506179
Study Section
Special Emphasis Panel (SSS (B8))
Project Start
1991-08-15
Project End
1994-08-31
Budget Start
1993-09-01
Budget End
1994-08-31
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Idec Pharmaceuticals Corporation
Department
Type
DUNS #
City
San Diego
State
CA
Country
United States
Zip Code
92121