Effect of inoculation with prion dilutions within the dynamic range of ELISA absorbance on prion incubation period

Authors: Cassmann, Eric; BROWN, QUAZETTA - Oak Ridge Institute For Science And Education (ORISE); FRESE, ALEXIS - Oak Ridge Institute For Science And Education (ORISE); LAMBERT, ZOE - Oak Ridge Institute For Science And Education (ORISE); WEST GREENLEE, HEATHER - Iowa State University; Greenlee, Justin

Submitted to: Veterinary Research Communications
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/2/2022
Publication Date: 10/11/2022
Citation: Cassmann, E.D., Brown, Q.L., Frese, A.J., Lambert, Z.J., West Greenlee, H.M., Greenlee, J.J. 2022. Effect of inoculation with prion dilutions within the dynamic range of ELISA absorbance on prion incubation period. Veterinary Research Communications. 46(4):1377-1380. https://doi.org/10.1007/s11259-022-10013-w.
DOI: https://doi.org/10.1007/s11259-022-10013-w

Interpretive Summary: Prion diseases are a group of diseases known as transmissible spongiform encephalopathies. These include scrapie in sheep and goats, chronic wasting disease in cervids, and bovine spongiform encephalopathy in cattle. These diseases have a very long incubation period lasting years in their natural host species. For this reason, experimental studies are often carried out in a mouse model. Even in mice, the incubation period can be influenced by the amount of infectious prion material in the inoculum. The purpose of this study was to determine the effect of dilutions within the ELISA dynamic range on the incubation period in mice. The results help interpret other experiments when ELISA is used to semi-quantitatively determine the amount of prion in the inoculum.

Technical Abstract: This study examines the effect of various infectious prion titers within the dynamic range as measured by ELISA on incubation period. We inoculated ovinized transgenic mice with seven decreasing dilutions of a fast-incubating scrapie strain. The highest inoculum group was a 20% w/v brain homogenate from a sheep with scrapie. The subsequent six inoculum dilutions ranged from the highest ELISA optical density reading of 4.000 to a dilution where scrapie prions were not detectable by ELISA. Multiple comparison analysis demonstrated variation in the incubation periods between some inoculum groups. Incubation periods were similar in inoculum groups unless their optical density differed by more than ˜2 units of absorbance. These data will inform the interpretation of future studies that compare incubation periods in experimentally inoculated animals for TSE research.