Anti-idiotypic antibodies: a new approach in prion research.

BACKGROUND: In certain cases, anti-idiotypic antibodies that recognize an antigen-combining site of an antibody can mimic the structure and/or function of certain nominal antigens. This feature makes them particularly useful if conventional experimental approaches fail to fulfil expectations, especially when the molecule of interest is infectious, toxic or difficult to isolate and purify. We suggest the application of an anti-idiotype concept to the field of prion biology, with the aim of evoking a humoral immune response against the pathological isoform of the prion protein (PrPSc). Different ways to induce anti-idiotypic responses were studied in mice and chickens using various forms of V5B2, a PrPSc-specific monoclonal antibody we have described previously. RESULTS: The preparation of anti-idiotypic monoclonal antibodies was achieved with well-defined strategies of immunization, selection and subsequent characterization. Our results demonstrate that it is possible to induce a strong anti-idiotypic immune response against the V5B2 monoclonal antibody in both xenogeneic and syngeneic experimental systems. From the competition seen between polyclonal and monoclonal anti-idiotypic antibodies and the original immunogen, the P1 peptide, and even more importantly, the ultimate target antigen, PrPSc, we conclude that selected antibodies bind to the antigen-combining site of the V5B2 monoclonal antibody and might even resemble the PrPSc-specific epitope. The involvement of both antigen-combining sites in the interaction between V5B2 and the most promising monoclonal anti-idiotypic antibody was further supported by molecular docking. CONCLUSION: The results of the present study not only provide an example of the successful production of Ab2 monoclonal antibodies based on a well planned strategy for selection, but should also provide a new experimental approach that is applicable to the field of prion diseases.

Creutzfeldt-Jakob disease in Slovenia from 1985 to 2003.

AIM: The epidemic of bovine spongiform encephalopathy and subsequent emergence of a new variant of Creutzfeldt-Jakob disease have raised great public concern, initiating improved and prospective surveillance of human prion diseases in Europe and all over the world. This report briefly presents the epidemiology, clinical data, neuropathology, immunohistochemistry, biochemistry, and prion-protein gene analysis of Slovenian cases of Creutzfeldt-Jakob disease from January 1985 to the end of 2003. MATERIALS, METHODS AND RESULTS: During the 19-year period, 39 suspected cases of Creutzfeldt-Jakob disease were referred and 22 were confirmed. The prion-protein gene was analyzed in 12 of the confirmed cases and the protein glycosylation pattern in 11. There was a low average incidence of Creutzfeldt-Jakob disease (0.5/million) throughout the surveillance period, but a pronounced increase between January 2001 and December 2003 (to 1.9/million/year). A high female to male ratio (2.5/1) was noted. All of the confirmed cases were defined as sporadic Creutzfeldt-Jakob disease based on the clinical data, neuropathological findings, glycosylation pattern, and gene analysis. All tested cases had a type-2 glycosylation pattern; eleven of the twelve tested patients were homozygous at codon 129 of the prion-protein gene (1 VV and 10 MM) and one was heterozygous. CONCLUSION: The small number of Slovenian cases of sporadic Creutzfeldt-Jakob disease during the last 19 years has shown a pronounced increase in incidence, reflecting improved surveillance, and a high female to male ratio, where female cases are more than twice as numerous as male cases.