Open AccessDifferential Toxicity of Antibodies to the Prion Protein
Author(s) -
Regina Reimann,
Tiziana Sonati,
Simone Hornemann,
U. Herrmann,
Michael Arand,
Simon Hawke,
Adriano Aguzzi
Publication year - 2016
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1005401
Subject(s) - neurotoxicity , antibody , epitope , monoclonal antibody , toxicity , immunotherapy , prion protein , biology , immunology , virology , medicine , pathology , immune system , disease
Antibodies against the prion protein PrP C can antagonize prion replication and neuroinvasion, and therefore hold promise as possible therapeutics against prion diseases. However, the safety profile of such antibodies is controversial. It was originally reported that the monoclonal antibody D13 exhibits strong target-related toxicity, yet a subsequent study contradicted these findings. We have reported that several antibodies against certain epitopes of PrP C , including antibody POM1, are profoundly neurotoxic, yet antibody ICSM18, with an epitope that overlaps with POM1, was reported to be innocuous when injected into mouse brains. In order to clarify this confusing situation, we assessed the neurotoxicity of antibodies D13 and ICSM18 with dose-escalation studies using diffusion-weighted magnetic resonance imaging and various histological techniques. We report that both D13 and ICSM18 induce rapid, dose-dependent, on-target neurotoxicity. We conclude that antibodies directed to this region may not be suitable as therapeutics. No such toxicity was found when antibodies against the flexible tail of PrP C were administered. Any attempt at immunotherapy or immunoprophylaxis of prion diseases should account for these potential untoward effects.