To more completely explore the possible therapeutic effect of anti-PrP antibodies, and to establish another system to analyze the influence of Abs on the conversion process, we screened Mabs produced in our laboratory for their capacity to inhibit PrP Sc formation. This screening was performed using N2a/22L cells and cell-free sPMCA. In N2a/22L cultures, all Mabs that react with mouse PrP reduce PrP Sc formation although with varying efficiency. Thus, similar to previous results [55] , we found that the ability to inhibit PrP C to PrP Sc conversion was not restricted to a single epitope or limited to a specific region of the protein. However, the greatest inhibition was observed with Mabs that targeted epitopes in the amino terminal, unstructured region of the PrP. The greatest inhibition in the N2a/22L cells was with Mab 5D6. This is consistent with a prior study using Mab 6D11 (anti-PrP residues 95-105) which in a screen of multiple Mabs, only one produced the greatest inhibition (,100%) [12] . Mab 6D11 has also been shown to have some efficacy in vivo prolonging the presymptomatic incubation period [57] . The Mab inhibition results obtained using PMCA were similar to that found in the cell culture system. PMCA has the advantages over the cell culture model of being cost-effective, simple, rapid, sensitive, and more amenable to studies of dose dependence. For identification of potential candidate Mabs that might have in vivo activity it is likely that such Mabs would have to produce 90 to 100% inhibition in the much simpler in vitro systems.