(1) Goals of project: - To determine the contribution of anti-HLA class II autoantibodies, generated in HIV-1 infected individuals due to homology with gp41, to their disease progression. - To determine whether uninfected volunteers, vaccinated with HIV-1 envelope-based vaccine develop anti-HLA class II autoantibodies. (2) Experimental approach: - Sequential Sera from HIV-1 patients participating in the MACS study are tested for the presence of cross-reactive anti-gp41/class II autoantibodies by ELISA. Their antibody titers are then correlated with their disease progression rate in terms of CD4 cell counts and clinical symptoms. - Sera from vaccinated volunteers are provided through the DAIDS group. Pre-immune and post-vaccination sera are screened for the presence of anti-class II autoantibodies. Titers are then correlated with the overall response to the vaccine and the to the vaccine dose used. (3) Major Findings: - In a cohort of HIV-1 infected hemophiliacs, and patients enrolled in the MACS study, high titers of CRab was found to correlate with rapid progression (2-4 yrs) to full blown AIDS. CRab Appear 2-3 yrs prior to CD4 decline. True stable patients have very low frequency of anti-class II CRab. We are currently continuing to study sera from patients in the MACS study to determine if the presence of CRab autoantibodies can be used as a predictive measurement preceding clinical deterioration. - We also tested sera from various vaccine groups who were immunized with subunit vaccines containing the gp41/HLA class II homologous region, for the presence of CRab. One seropositive vaccine group showed marked elevation in CRab titers following vaccination.

Agency
National Institute of Health (NIH)
Institute
Food and Drug Administration (FDA)
Type
Intramural Research (Z01)
Project #
1Z01BK003002-03
Application #
5200711
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost