Previously we have discovered a public idiotope, designated 1F7, that is expressed on antibodies against HIV type 1 (HIV-1) in human and nonhuman primates. To test the potential of mouse monoclonal antibody (mAb) 1F7 as a therapeutic anti-clonotypic antibody in HIV-1-infected patients, we used the simian HIV-IIIB macaque infection model, which mimics several immunological and pathological characteristics of HIV-1 infection in humans. Four healthy simian HIV-infected rhesus monkeys (Macaca mulatta) expressing the 1F7 marker on anti-gp120 antibodies were selected for this study. Three monkeys of this group were immunized several times with the murine mAb 1F7 i.v., and one monkey received as control an isotype-matched antibody, TEPC183. No serious side effect or allergic reaction was encountered. Blood collected before and during the immunization and over several months afterward were analyzed for neutralizing antibodies. Significant increases in breadth and potency of HIV-1-neutralizing antibody titers to one or more virus strains were detected in all three of the 1F7-immunized monkeys, but not in the control monkey immunized with TEPC183. These results show that an antibody, recognizing a public idiotope associated with anti-HIV-1 antibodies can function in chronically infected primates as an anti-clonotypic immunogen to boost antibodies that neutralize homologous and heterologous virus strains. This study represents a first step toward the preclinical evaluation of 1F7 as a therapeutic AIDS vaccine.

Latent structure analysis can be used to determine sensitivity and specificity rates of human immunodeficiency virus antibody assays in the absence of previous clinical or laboratory results. The technique was applied to the analysis of data obtained when a panel of serum samples, collected as part of a large-scale screening project, were subjected to four conventional bioassays (ag121, p24, gp120, and an enzyme-linked immunosorbent assay). To determine the accuracy of this statistical approach, the results of latent structure analysis were compared with the known clinical diagnoses of patients from whom the samples were taken, and nearly 100% agreement was obtained. Although a two-class latent structure model had some predictive value, a three-class model more adequately explained assay patterns. The use of the four standard assays in conjunction with the statistical methods described here would largely reduce the need for confirmatory Western blot assays in analyses of large panels of samples.