학술논문
Immunization with Genetically Modified Trypanosomes Provides Protection against Transmissible Spongiform Encephalopathies.
Document Type
Academic Journal
Author
Triller G; Laboratory of Lymphocyte Biology, The Rockefeller University, New York, NY 10065, USA.; Garyfallos DA; Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), University of Cambridge, Puddicombe Way, Cambridge CB2 0AW, UK.; Papavasiliou FN; Division of Immune Diversity, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany.; Sklaviadis T; Laboratory of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.; Stavropoulos P; Laboratory of Lymphocyte Biology, The Rockefeller University, New York, NY 10065, USA.; Xanthopoulos K; Laboratory of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.; Institute of Applied Biosciences, Centre for Research and Technology Hellas, 57001 Thermi, Greece.
Source
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
Subject
Language
English
Abstract
Transmissible spongiform encephalopathies are incurable neurodegenerative diseases, associated with the conversion of the physiological prion protein to its disease-associated counterpart. Even though immunization against transmissible spongiform encephalopathies has shown great potential, immune tolerance effects impede the use of active immunization protocols for successful prophylaxis. In this study, we evaluate the use of trypanosomes as biological platforms for the presentation of a prion antigenic peptide to the host immune system. Using the engineered trypanosomes in an immunization protocol without the use of adjuvants led to the development of a humoral immune response against the prion protein in wild type mice, without the appearance of adverse reactions. The immune reaction elicited with this protocol displayed in vitro therapeutic potential and was further evaluated in a bioassay where immunized mice were partially protected in a representative murine model of prion diseases. Further studies are underway to better characterize the immune reaction and optimize the immunization protocol.