The PrP-specific Mabs that were evaluated for their ability to prevent PrP C to PrP Sc conversion have linear epitopes that span the entire prion protein from the amino to the carboxy terminus ( Table 1 , Fig. 1 ). We used N2a cells persistently infected with the 22L mouseadapted scrapie strain (N2a/22L) to evaluate the affect of each Mab on PrP Sc formation ( Fig. 2A and 2B) . Treatment with the Mabs did not result in any cytotoxicity to the N2a/22L cells throughout the incubation period. Further, incubation of the. N2a/22L cells with 10 mg/ml purified, irrelevant mouse IgG had no effect on PrP Sc formation compared to untreated N2a/22L cultures (Figs. 2A and 2B). Mab 3F4 did not reduce PrP Sc formation compared to control N2a/22L cultures lacking Mab. Mab 3F4 does not react with mouse prion protein so this was not surprising [38] . The ability of a singly added Mab to inhibit PrP Sc formation was not related to a specific epitope since all of the remaining singly added Mabs inhibited PrP Sc formation to varying degrees. Of the individually added Mabs, 5D6 was the most effective at inhibiting PrP Sc formation (95% inhibition) while 3A2 was the least effective (38% inhibition). Targeting the amino terminus with Mab 7E4 was effective at inhibiting 73% PrP Sc formation as was targeting the octapeptide repeat region using Mab 10E4 which resulted in almost 90% inhibition. Strangely, although their epitopes overlap, Mab 11F12 was less effective than Mab 5D6 at inhibiting PrP Sc formation (53% vs 95% inhibition). This is in contrast to Mabs 8E9 and 1B11, which have overlapping epitopes with 8E9 being more expansive, and resulted in 52% and 42% inhibition, respectively. The combination of 5D6 and 11F12 did not result in an additive inhibitory effect and, in fact, resulted in less inhibition than either one alone. This was confirmed in studies where the addition of 8E9 to 5D6 and 11F12 caused a 45% PrP Sc inhibition, which was slightly better than 8E9 alone, although the predicted additive inhibitory effect of 63% for the three Mab combination (48% for 8E9 plus 15% for the 5D6 and 11F12 combination) was not observed.