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Abstract

Antibodies are disclosed which specifically bind to native PrPin situ. Preferred antibodies bind only to the native PrPof a particular species e.g., human, cow, sheep, pig, etc. Particularly preferred antibodies bind specifically to a particular isoform of human PrP. Preferred antibodies of the invention are (1) produced by phage display methodology, (2) bind specifically to native PrP, (3) neutralizes the infectivity of prions, (4) bind to PrPin situ and (5) bind 50% or more of PrPin a liquid flowable sample. Antibodies of the invention can be bound to a substrate and used to assay a sample (which has any PrPdenatured via proteinase K) for the presence of PrPof a specific species which PrPis associated with disease. Antibodies which specifically bind to human PrPcan be labeled and injected carrying out an in vivo diagnostic test to determine if the human is infected with prions associated with disease. The antibodies are preferably produced using phage display technology wherein the genetic material in the phage expressing the antibody is obtained from a mammal with an ablated endogenous PrP protein gene and an endogenous chimeric PrP gene which mammal had been inoculated with PrPto induce antibody production.