Advances in the development of antibody-based immunotherapy against prion disease

References

• Prusiner SB. The prion diseases. Brain Pathol. 1998;8(3):499–513.
   PubMed Web of Science ®Google Scholar
• McKinley MP, Bolton DC, Prusiner SB. A protease-resistant protein is a structural component of the scrapie prion. Cell. 1983;35(1):57–62.
   Web of Science ®Google Scholar
• Prusiner SB. Molecular biology of prion diseases. Science. 1991; 252(5012):1515–1522.
   PubMed Web of Science ®Google Scholar
• Collinge J. Prion diseases of humans and animals: their causes and molecular basis. Annu Rev Neurosci. 2001;24:519–550.
   PubMed Web of Science ®Google Scholar
• Brown P. Creutzfeldt-Jakob disease: reflections on the risk from blood product therapy. Haemophilia. 2007;13 Suppl 5:33–40.
   Google Scholar
• Wisniewski T, Sigurdsson EM. Therapeutic approaches for prion and Alzheimer’s diseases. FEBS J. 2007;274(15):3784–3798.
   PubMed Web of Science ®Google Scholar
• Béringue V, Herzog L, Jaumain E, et al. Facilitated cross-species transmission of prions in extraneural tissue. Science. 2012;335(6067):472–475.
   Web of Science ®Google Scholar
• Brody DL, Holtzman DM. Active and passive immunotherapy for neurodegenerative disorders. Annu Rev Neurosci. 2008;31:175–193.
   PubMed Web of Science ®Google Scholar
• Windl O, Dempster M, Estibeiro P, Lathe R. A candidate marsupial PrP gene reveals two domains conserved in mammalian PrP proteins. Gene. 1995;159(2):181–186.
   Web of Science ®Google Scholar
• Harris DA, Lele P, Snider WD. Localization of the mRNA for a chicken prion protein by in situ hybridization. Proc Natl Acad Sci U S A. 1993;90(9):4309–4313.
   Web of Science ®Google Scholar
• Oesch B, Westaway D, Wälchli M, et al. A cellular gene encodes scrapie PrP 27-30 protein. Cell. 1985;40(4):735–746.
   PubMed Web of Science ®Google Scholar
• Harris DA. Cellular biology of prion diseases. Clin Microbiol Rev. 1999;12(3):429–444.
   Web of Science ®Google Scholar
• Kretzschmar HA, Prusiner SB, Stowring LE, DeArmond SJ. Scrapie prion proteins are synthesized in neurons. Am J Pathol. 1986; 122(1):1–5.
   Web of Science ®Google Scholar
• Dodelet VC, Cashman NR. Prion protein expression in human leukocyte differentiation. Blood. 1998;91(5):1556–1561.
   Web of Science ®Google Scholar
• Büeler H, Aguzzi A, Sailer A, et al. Mice devoid of PrP are resistant to scrapie. Cell. 1993;73(7):1339–1347.
   PubMed Web of Science ®Google Scholar
• Büeler H, Fischer M, Lang Y, et al. Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein. Nature. 1992;356(6370):577–582.
   PubMed Web of Science ®Google Scholar
• Colling SB, Khana M, Collinge J, Jefferys JG. Mossy fibre reorganization in the hippocampus of prion protein null mice. Brain Res. 1997;755(1):28–35.
   Web of Science ®Google Scholar
• Tobler I, Gaus SE, Deboer T, et al. Altered circadian activity rhythms and sleep in mice devoid of prion protein. Nature. 1996;380(6575):639–642.
   PubMed Web of Science ®Google Scholar
• Herms JW, Tings T, Dunker S, Kretzschmar HA. Prion protein affects Ca2+-activated K+ currents in cerebellar purkinje cells. Neurobiol Dis. 2001;8(2):324–330.
   Web of Science ®Google Scholar
• Stöckel J, Safar J, Wallace AC, Cohen FE, Prusiner SB. Prion protein selectively binds copper(II) ions. Biochemistry. 1998;37(20):7185–7193.
   PubMed Web of Science ®Google Scholar
• Brown DR, Mohn CM. Astrocytic glutamate uptake and prion protein expression. Glia. 1999;25(3):282–292.
   Web of Science ®Google Scholar
• Milhavet O, Lehmann S. Oxidative stress and the prion protein in transmissible spongiform encephalopathies. Brain Res Brain Res Rev. 2002;38(3):328–339.
   PubMedGoogle Scholar
• Brown DR, Schulz-Schaeffer WJ, Schmidt B, Kretzschmar HA. Prion protein-deficient cells show altered response to oxidative stress due to decreased SOD-1 activity. Exp Neurol. 1997;146(1):104–112.
   Web of Science ®Google Scholar
• Roucou X, LeBlanc AC. Cellular prion protein neuroprotective function: implications in prion diseases. J Mol Med (Berl). 2005;83(1):3–11.
   Web of Science ®Google Scholar
• Roucou X, Gains M, LeBlanc AC. Neuroprotective functions of prion protein. J Neurosci Res. 2004;75(2):153–161.
   PubMed Web of Science ®Google Scholar
• Borchelt DR, Scott M, Taraboulos A, Stahl N, Prusiner SB. Scrapie and cellular prion proteins differ in their kinetics of synthesis and topology in cultured cells. J Cell Biol. 1990;110(3):743–752.
   Web of Science ®Google Scholar
• Caughey B, Raymond GJ. The scrapie-associated form of PrP is made from a cell surface precursor that is both protease- and phospholipase-sensitive. J Biol Chem. 1991;266(27):18217–18223.
   Web of Science ®Google Scholar
• Stahl N, Baldwin MA, Teplow DB, et al. Structural studies of the scrapie prion protein using mass spectrometry and amino acid sequencing. Biochemistry. 1993;32(8):1991–2002.
   PubMed Web of Science ®Google Scholar
• Bugiani O, Giaccone G, Piccardo P, Morbin M, Tagliavini F, Ghetti B. Neuropathology of Gerstmann-Straussler-Scheinker disease. Microsc Res Tech. 2000;50(1):10–15.
   PubMed Web of Science ®Google Scholar
• Ghetti B1, Piccardo P, Frangione B, et al. Prion protein amyloidosis. Brain Pathol. 1996;6(2):127–145.
   Web of Science ®Google Scholar
• Aguzzi A, Heikenwalder M. Pathogenesis of prion diseases: current status and future outlook. Nat Rev Microbiol. 2006;4(10):765–775.
   PubMed Web of Science ®Google Scholar
• Cashman NR, Loertscher R, Nalbantoglu J, et al. Cellular isoform of the scrapie agent protein participates in lymphocyte activation. Cell. 1990;61(1):185–192.
   Web of Science ®Google Scholar
• Meiner Z, Halimi M, Polakiewicz RD, Prusiner SB, Gabizon R. Presence of prion protein in peripheral tissues of Libyan Jews with Creutzfeldt-Jakob disease. Neurology. 1992;42(7):1355–1360.
   Web of Science ®Google Scholar
• Bessos H, Drummond O, Prowse C, Turner M, MacGregor I. The release of prion protein from platelets during storage of apheresis platelets. Transfusion. 2001;41(1):61–66.
   Web of Science ®Google Scholar
• Heppner FL, Christ AD, Klein MA, et al. Transepithelial prion transport by M cells. Nat Med. 2001;7(9):976–977.
   PubMed Web of Science ®Google Scholar
• Aguzzi A, Sigurdson CJ. Antiprion immunotherapy: to suppress or to stimulate? Nat Rev Immunol. 2004;4(9):725–736.
   Web of Science ®Google Scholar
• Heikenwalder M, Prinz M, Heppner FL, Aguzzi A. Current concepts and controversies in prion immunopathology. J Mol Neurosci. 2004;23(1–2):3–12.
   Web of Science ®Google Scholar
• Glatzel M, Abela E, Maissen M, Aguzzi A. Extraneural pathologic prion protein in sporadic Creutzfeldt-Jakob disease. N Engl J Med. 2003;349(19):1812–1820.
   PubMed Web of Science ®Google Scholar
• Daude N. Prion diseases and the spleen. Viral Immunol. 2004;17(3):334–349.
   Web of Science ®Google Scholar
• Kimberlin RH, Walker CA. The role of the spleen in the neuroinvasion of scrapie in mice. Virus Res. 1989;12(3):201–211.
   Web of Science ®Google Scholar
• Park CS, Choi YS. How do follicular dendritic cells interact intimately with B cells in the germinal centre? Immunology. 2005;114(1):2–10.
   Web of Science ®Google Scholar
• Beekes M, McBride PA. The spread of prions through the body in naturally acquired transmissible spongiform encephalopathies. FEBS J. 2007;274(3):588–605.
   Web of Science ®Google Scholar
• Glaysher BR, Mabbott NA. Role of the GALT in scrapie agent neuroinvasion from the intestine. J Immunol. 2007;178(6):3757–3766.
   Web of Science ®Google Scholar
• Sigurdson CJ, Williams ES, Miller MW, Spraker TR, O’Rourke KI, Hoover EA. Oral transmission and early lymphoid tropism of chronic wasting disease PrPres in mule deer fawns (Odocoileus hemionus). J Gen Virol. 1999;80(Pt 10):2757–2764.
   PubMedGoogle Scholar
• Klein MA, Kaeser PS, Schwarz P, et al. Complement facilitates early prion pathogenesis. Nat Med. 2001;7(4):488–492.
   PubMed Web of Science ®Google Scholar
• Mabbott NA, Williams A, Farquhar CF, Pasparakis M, Kollias G, Bruce ME. Tumor necrosis factor alpha-deficient, but not interleukin-6-deficient, mice resist peripheral infection with scrapie. J Virol. 2000;74(7):3338–3344.
   Web of Science ®Google Scholar
• Prinz M, Montrasio F, Klein MA, et al. Lymph nodal prion replication and neuroinvasion in mice devoid of follicular dendritic cells. Proc Natl Acad Sci U S A. 2002;99(2):919–924.
   Web of Science ®Google Scholar
• Montrasio F, Frigg R, Glatzel M, et al. Impaired prion replication in spleens of mice lacking functional follicular dendritic cells. Science. 2000;288(5469):1257–1259.
   Web of Science ®Google Scholar
• Mabbott NA, Mackay F, Minns F, Bruce ME. Temporary inactivation of follicular dendritic cells delays neuroinvasion of scrapie. Nat Med. 2000;6(7):719–720.
   Web of Science ®Google Scholar
• Mabbott NA, Bruce ME, Botto M, Walport MJ, Pepys MB. Temporary depletion of complement component C3 or genetic deficiency of C1q significantly delays onset of scrapie. Nat Med. 2001;7(4):485–487.
   PubMed Web of Science ®Google Scholar
• Pocchiari M, Schmittinger S, Masullo C. Amphotericin B delays the incubation period of scrapie in intracerebrally inoculated hamsters. J Gen Virol. 1987;68(Pt 1):219–223.
   PubMed Web of Science ®Google Scholar
• Tagliavini F, McArthur RA, Canciani B, et al. Effectiveness of anthracycline against experimental prion disease in Syrian hamsters. Science. 1997;276(5315):1119–1122.
   PubMed Web of Science ®Google Scholar
• Ingrosso L, Ladogana A, Pocchiari M. Congo red prolongs the incubation period in scrapie-infected hamsters. J Virol. 1995;69(1):506–508.
   PubMed Web of Science ®Google Scholar
• Ehlers B, Diringer H. Dextran sulphate 500 delays and prevents mouse scrapie by impairment of agent replication in spleen. J Gen Virol. 1984;65(Pt 8):1325–1330.
   Google Scholar
• Farquhar CF, Dickinson AG. Prolongation of scrapie incubation period by an injection of dextran sulphate 500 within the month before or after infection. J Gen Virol. 1986;67(Pt 3):463–473.
   PubMedGoogle Scholar
• Kimberlin RH, Walker CA. Suppression of scrapie infection in mice by heteropolyanion 23, dextran sulfate, and some other polyanions. Antimicrob Agents Chemother. 1986;30(3):409–413.
   PubMed Web of Science ®Google Scholar
• Soto C, Kascsak RJ, Saborío GP, et al. Reversion of prion protein conformational changes by synthetic beta-sheet breaker peptides. Lancet. 2000;355(9199):192–197.
   PubMed Web of Science ®Google Scholar
• Schenk D, Barbour R, Dunn W, et al. Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature. 1999;400(6740):173–177.
   PubMed Web of Science ®Google Scholar
• Bard F, Cannon C, Barbour R, et al. Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nat Med. 2000;6(8):916–919.
   PubMed Web of Science ®Google Scholar
• Morgan D, Diamond DM, Gottschall PE, et al. A beta peptide vaccination prevents memory loss in an animal model of Alzheimer’s disease. Nature. 2000;408(6815):982–985.
   PubMed Web of Science ®Google Scholar
• Hu W, Rosenberg RN, Stuve O. Prion proteins: a biological role beyond prion diseases. Acta Neurol Scand. 2007;116(2):75–82.
   Web of Science ®Google Scholar
• Korth C, Peters PJ. Emerging pharmacotherapies for Creutzfeldt-Jakob disease. Arch Neurol. 2006;63(4):497–501.
   PubMedGoogle Scholar
• Enari M, Flechsig E, Weissmann C. Scrapie prion protein accumulation by scrapie-infected neuroblastoma cells abrogated by exposure to a prion protein antibody. Proc Natl Acad Sci U S A. 2001;98(16):9295–9299.
   PubMed Web of Science ®Google Scholar
• Peretz D, Williamson RA, Kaneko K, et al. Antibodies inhibit prion propagation and clear cell cultures of prion infectivity. Nature. 2001;412(6848):739–743.
   PubMed Web of Science ®Google Scholar
• White AR, Enever P, Tayebi M, et al. Monoclonal antibodies inhibit prion replication and delay the development of prion disease. Nature. 2003;422(6927):80–83.
   PubMed Web of Science ®Google Scholar
• Polymenidou M, Heppner FL, Pellicioli EC, et al. Humoral immune response to native eukaryotic prion protein correlates with anti-prion protection. Proc Natl Acad Sci U S A. 2004;101 Suppl 2:14670–14676.
   Google Scholar
• Aucouturier P, Carnaud C. The immune system and prion diseases: a relationship of complicity and blindness. J Leukoc Biol. 2002;72(6):1075–1083.
   Web of Science ®Google Scholar
• Heppner FL, et al. Prevention of scrapie pathogenesis by transgenic expression of anti-prion protein antibodies. Science. 2001;294(5540):178–182.
   PubMed Web of Science ®Google Scholar
• Korth C, Streit P, Oesch B. Monoclonal antibodies specific for the native, disease-associated isoform of the prion protein. Methods Enzymol. 1999;309:106–122.
   PubMed Web of Science ®Google Scholar
• Bade S, Frey A. Potential of active and passive immunizations for the prevention and therapy of transmissible spongiform encephalopathies. Expert Rev Vaccines. 2007;6(2):153–168.
   PubMed Web of Science ®Google Scholar
• Krasemann S, Groschup MH, Harmeyer S, Hunsmann G, Bodemer W. Generation of monoclonal antibodies against human prion proteins in PrP0/0 mice. Mol Med. 1996;2(6):725–734.
   PubMed Web of Science ®Google Scholar
• Demart S, Fournier JG, Creminon C, et al. New insight into abnormal prion protein using monoclonal antibodies. Biochem Biophys Res Commun. 1999;265(3):652–657.
   PubMed Web of Science ®Google Scholar
• Gregoire S, Logre C, Metharom P, et al. Identification of two immunogenic domains of the prion protein – PrP – which activate class II-restricted T cells and elicit antibody responses against the native molecule. J Leukoc Biol. 2004;76(1):125–134.
   Web of Science ®Google Scholar
• Bainbridge J, Walker B. Cell mediated immune responses against human prion protein. Clin Exp Immunol. 2003;133(3):310–317.
   Web of Science ®Google Scholar
• Kim CL, Umetani A, Matsui T, Ishiguro N, Shinagawa M, Horiuchi M. Antigenic characterization of an abnormal isoform of prion protein using a new diverse panel of monoclonal antibodies. Virology. 2004;320(1):40–51.
   Web of Science ®Google Scholar
• Khalili-Shirazi A, Quaratino S, Londei M, et al. Protein conformation significantly influences immune responses to prion protein. J Immunol. 2005;174(6):3256–3263.
   PubMed Web of Science ®Google Scholar
• Nakamura N, Miyamoto K, Shimokawa M, et al. Generation of antibodies against prion protein by scrapie-infected cell immunization of PrP(0/0) mice. Hybrid Hybridomics. 2003;22(4):263–266.
   Google Scholar
• Handisurya A, Gilch S, Winter D, et al. Vaccination with prion peptide-displaying papillomavirus-like particles induces autoantibodies to normal prion protein that interfere with pathologic prion protein production in infected cells. FEBS J. 2007;274(7):1747–1758.
   PubMed Web of Science ®Google Scholar
• Barry RA, McKinley MP, Bendheim PE, Lewis GK, DeArmond SJ, Prusiner SB. Antibodies to the scrapie protein decorate prion rods. J Immunol. 1985;135(1):603–613.
   Web of Science ®Google Scholar
• Bockman JM, Kingsbury DT. Immunological analysis of host and agent effects on Creutzfeldt-Jakob disease and scrapie prion proteins. J Virol. 1988;62(9):3120–3127.
   Web of Science ®Google Scholar
• Koller MF, Grau T, Christen P. Induction of antibodies against murine full-length prion protein in wild-type mice. J Neuroimmunol. 2002;132(1–2):113–116.
   Web of Science ®Google Scholar
• Del Giudice G. Hsp70: a carrier molecule with built-in adjuvanticity. Experientia. 1994;50(11–12):1061–1066.
   Google Scholar
• Sigurdsson EM, Brown DR, Daniels M, et al. Immunization delays the onset of prion disease in mice. Am J Pathol. 2002;161(1):13–17.
   PubMed Web of Science ®Google Scholar
• Ishibashi D, Yamanaka H, Yamaguchi N, et al. Immunization with recombinant bovine but not mouse prion protein delays the onset of disease in mice inoculated with a mouse-adapted prion. Vaccine. 2007;25(6):985–992.
   Web of Science ®Google Scholar
• Tayebi M, Collinge J, Hawke S. Unswitched immunoglobulin M response prolongs mouse survival in prion disease. J Gen Virol. 2009;90(Pt 3):777–782.
   Google Scholar
• Roettger Y, Du Y, Bacher M, Zerr I, Dodel R, Bach JP. Immunotherapy in prion disease. Nat Rev Neurol. 2013;9(2):98–105.
   PubMed Web of Science ®Google Scholar
• Arbel M, Lavie V, Solomon B. Generation of antibodies against prion protein in wild-type mice via helix 1 peptide immunization. J Neuroimmunol. 2003;144(1–2):38–45.
   Web of Science ®Google Scholar
• Bainbridge J, Jones N, Walker B. Multiple antigenic peptides facilitate generation of anti-prion antibodies. Clin Exp Immunol. 2004;137(2):298–304.
   Web of Science ®Google Scholar
• Souan L, Tal Y, Felling Y, Cohen IR, Taraboulos A, Mor F. Modulation of proteinase-K resistant prion protein by prion peptide immunization. Eur J Immunol. 2001;31(8):2338–2346.
   PubMed Web of Science ®Google Scholar
• Schwarz A, Krätke O, Burwinkel M, et al. Immunisation with a synthetic prion protein-derived peptide prolongs survival times of mice orally exposed to the scrapie agent. Neurosci Lett. 2003;350(3):187–189.
   PubMed Web of Science ®Google Scholar
• Bachy V, Ballerini C, Gourdain P, et al. Mouse vaccination with dendritic cells loaded with prion protein peptides overcomes tolerance and delays scrapie. J Gen Virol. 2010;91(Pt 3):809–820.
   Google Scholar
• Xanthopoulos K, Lagoudaki R, Kontana A, et al. Immunization with recombinant prion protein leads to partial protection in a murine model of TSEs through a novel mechanism. PLoS One. 2013;8(3):e59143.
   Web of Science ®Google Scholar
• Bade S, Baier M, Boetel T, Frey A. Intranasal immunization of Balb/c mice against prion protein attenuates orally acquired transmissible spongiform encephalopathy. Vaccine. 2006;24(9):1242–1253.
   Web of Science ®Google Scholar
• Goñi F, Knudsen E, Schreiber F, et al. Mucosal vaccination delays or prevents prion infection via an oral route. Neuroscience. 2005;133(2):413–421.
   Web of Science ®Google Scholar
• Goñi F, Prelli F, Schreiber F, et al. High titers of mucosal and systemic anti-PrP antibodies abrogate oral prion infection in mucosal-vaccinated mice. Neuroscience. 2008;153(3):679–686.
   Web of Science ®Google Scholar
• Solforosi L, Criado JR, McGavern DB, et al. Cross-linking cellular prion protein triggers neuronal apoptosis in vivo. Science. 2004; 303(5663):1514–1516.
   PubMed Web of Science ®Google Scholar
• Lefebvre-Roque M, Kremmer E, Gilch S, et al. Toxic effects of intracerebral PrP antibody administration during the course of BSE infection in mice. Prion. 2007;1(3):198–206.
   PubMed Web of Science ®Google Scholar
• Wang F, Wang X, Yuan CG, Ma J. Generating a prion with bacterially expressed recombinant prion protein. Science. 2010;327(5969):1132–1135.
   PubMed Web of Science ®Google Scholar
• Ishibashi D, Yamanaka H, Mori T, et al. Antigenic mimicry-mediated anti-prion effects induced by bacterial enzyme succinylarginine dihydrolase in mice. Vaccine. 2011;29(50):9321–9328.
   Web of Science ®Google Scholar
• Hamanaka T, Sakasegawa Y, Ohmoto A, Kimura T, Ando T, Doh-ura K. Anti-prion activity of protein-bound polysaccharide K in prion-infected cells and animals. Biochem Biophys Res Commun. 2011;405(2):285–290.
   Web of Science ®Google Scholar
• Beringue V, Vilette D, Mallinson G, et al. PrPSc binding antibodies are potent inhibitors of prion replication in cell lines. J Biol Chem. 2004;279(38):39671–39676.
   Web of Science ®Google Scholar
• Cardinale A, Filesi I, Vetrugno V, Pocchiari M, Sy MS, Biocca S. Trapping prion protein in the endoplasmic reticulum impairs PrPC maturation and prevents PrPSc accumulation. J Biol Chem. 2005;280(1):685–694.
   PubMed Web of Science ®Google Scholar
• Féraudet C, Morel N, Simon S, et al. Screening of 145 anti-PrP monoclonal antibodies for their capacity to inhibit PrPSc replication in infected cells. J Biol Chem. 2005;280(12):11247–11258.
   PubMed Web of Science ®Google Scholar
• Kim CL, Karino A, Ishiguro N, Shinagawa M, Sato M, Horiuchi M. Cell-surface retention of PrPC by anti-PrP antibody prevents protease-resistant PrP formation. J Gen Virol. 2004;85(Pt 11):3473–3482.
   Google Scholar
• Perrier V, Solassol J, Crozet C, et al. Anti-PrP antibodies block PrPSc replication in prion-infected cell cultures by accelerating PrPC degradation. J Neurochem. 2004;89(2):454–463.
   PubMed Web of Science ®Google Scholar
• Gabizon R, McKinley MP, Groth D, Prusiner SB. Immunoaffinity purification and neutralization of scrapie prion infectivity. Proc Natl Acad Sci U S A. 1988;85(18):6617–6621.
   Web of Science ®Google Scholar
• Horiuchi M, Caughey B. Specific binding of normal prion protein to the scrapie form via a localized domain initiates its conversion to the protease-resistant state. EMBO J. 1999;18(12):3193–3203.
   Web of Science ®Google Scholar
• Sigurdsson EM, Sy MS, Li R, et al. Anti-prion antibodies for prophylaxis following prion exposure in mice. Neurosci Lett. 2003;336(3):185–187.
   PubMed Web of Science ®Google Scholar
• Song CH, Furuoka H, Kim CL, et al. Effect of intraventricular infusion of anti-prion protein monoclonal antibodies on disease progression in prion-infected mice. J Gen Virol. 2008;89(Pt 6):1533–1544.
   PubMed Web of Science ®Google Scholar
• Moda F, Vimercati C, Campagnani I, et al. Brain delivery of AAV9 expressing an anti-PrP monovalent antibody delays prion disease in mice. Prion. 2012;6(4):383–390.
   PubMed Web of Science ®Google Scholar
• Jones DR, Taylor WA, Bate C, David M, Tayebi M. A camelid anti-PrP antibody abrogates PrP replication in prion-permissive neuroblastoma cell lines. PLoS One. 2010;5(3):e9804.
   PubMed Web of Science ®Google Scholar
• Skrlj N, Drevenšek G, Hudoklin S, Romih R, Curin Šerbec V, Dolinar M. Recombinant single-chain antibody with the Trojan peptide penetratin positioned in the linker region enables cargo transfer across the blood-brain barrier. Appl Biochem Biotechnol. 2013;169(1):159–169.
   PubMed Web of Science ®Google Scholar
• Vana K, Zuber C, Pflanz H, et al. LRP/LR as an alternative promising target in therapy of prion diseases, Alzheimer’s disease and cancer. Infect Disord Drug Targets. 2009;9(1):69–80.
   PubMedGoogle Scholar
• Sadowski MJ, Pankiewicz J, Prelli F, et al. Anti-PrP Mab 6D11 suppresses PrP(Sc) replication in prion infected myeloid precursor line FDC-P1/22L and in the lymphoreticular system in vivo. Neurobiol Dis. 2009;34(2):267–278.
   PubMed Web of Science ®Google Scholar
• Ohsawa N, Song CH, Suzuki A, Furuoka H, Hasebe R, Horiuchi M. Therapeutic effect of peripheral administration of an anti-prion protein antibody on mice infected with prions. Microbiol Immunol. 2013;57(4):288–297.
   Web of Science ®Google Scholar
• Féraudet-Tarisse C, Andréoletti O, Morel N, et al. Immunotherapeutic effect of anti-PrP monoclonal antibodies in transmissible spongiform encephalopathy mouse models: pharmacokinetic and pharmacodynamic analysis. J Gen Virol. 2010;91(Pt 6):1635–1645.
   Google Scholar
• Donofrio G, Heppner FL, Polymenidou M, Musahl C, Aguzzi A. Paracrine inhibition of prion propagation by anti-PrP single-chain Fv miniantibodies. J Virol. 2005;79(13):8330–8338.
   PubMed Web of Science ®Google Scholar
• Klöhn PC, Farmer M, Linehan JM, et al. PrP antibodies do not trigger mouse hippocampal neuron apoptosis. Science. 2012;335(6064):52.
   PubMed Web of Science ®Google Scholar
• Ahmad ZA, Yeap SK, Ali AM, Ho WY, Alitheen NB, Hamid M. scFv antibody: principles and clinical application. Clin Dev Immunol. 2012;2012:980250.
   PubMed Web of Science ®Google Scholar
• Malone J, Sullivan MA. Analysis of antibody selection by phage display utilizing anti-phenobarbital antibodies. J Mol Recognit. 1996;9(5–6):738–745.
   Web of Science ®Google Scholar
• Vaughan TJ, Williams AJ, Pritchard K, et al. Human antibodies with sub-nanomolar affinities isolated from a large non-immunized phage display library. Nat Biotechnol. 1996;14(3):309–314.
   PubMed Web of Science ®Google Scholar
• Brockmann EC. Selection of stable scFv antibodies by phage display. Methods Mol Biol. 2012;907:123–144.
   Google Scholar
• Flego M, Ascione A, Zamboni S, Dupuis ML, Imperiale V, Cianfriglia M. Generation of human scFvs antibodies recognizing a prion protein epitope expressed on the surface of human lymphoblastoid cells. BMC Biotechnol. 2007;7:38.
   Web of Science ®Google Scholar
• Kaplitt MG, Feigin A, Tang C, et al. Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson’s disease: an open label, phase I trial. Lancet. 2007;369(9579):2097–2105.
   PubMed Web of Science ®Google Scholar
• Marks WJ Jr, Bartus RT, Siffert J, et al. Gene delivery of AAV2-neurturin for Parkinson’s disease: a double-blind, randomised, controlled trial. Lancet Neurol. 2010;9(12):1164–1172.
   PubMed Web of Science ®Google Scholar
• Mandel RJ. CERE-110, an adeno-associated virus-based gene delivery vector expressing human nerve growth factor for the treatment of Alzheimer’s disease. Curr Opin Mol Ther. 2010;12(2):240–247.
   PubMed Web of Science ®Google Scholar
• Burger C, Nash K, Mandel RJ. Recombinant adeno-associated viral vectors in the nervous system. Hum Gene Ther. 2005;16(7):781–791.
   Web of Science ®Google Scholar
• Mandel RJ, Manfredsson FP, Foust KD, et al. Recombinant adeno-associated viral vectors as therapeutic agents to treat neurological disorders. Mol Ther. 2006;13(3):463–483.
   PubMed Web of Science ®Google Scholar
• Wuertzer CA, Sullivan MA, Qiu X, Federoff HJ. CNS delivery of vectored prion-specific single-chain antibodies delays disease onset. Mol Ther. 2008;16(3):481–486.
   PubMed Web of Science ®Google Scholar
• Stanker LH, Scotcher MC, Lin A, McGarvey J, Prusiner SB, Hnasko R. Novel epitopes identified by anti-PrP monoclonal antibodies produced following immunization of Prnp0/0 Balb/cJ mice with purified scrapie prions. Hybridoma (Larchmt). 2012;31(5):314–324.
   Google Scholar
• Gauczynski S, Nikles D, El-Gogo S, et al. The 37-kDa/67-kDa laminin receptor acts as a receptor for infectious prions and is inhibited by polysulfated glycanes. J Infect Dis. 2006;194(5):702–709.
   PubMed Web of Science ®Google Scholar
• Gauczynski S, Peyrin JM, Haïk S, et al. The 37-kDa/67-kDa laminin receptor acts as the cell-surface receptor for the cellular prion protein. EMBO J. 2001;20(21):5863–5875.
   PubMed Web of Science ®Google Scholar
• Leucht C, Simoneau S, Rey C, et al. The 37 kDa/67 kDa laminin receptor is required for PrP(Sc) propagation in scrapie-infected neuronal cells. EMBO Rep. 2003;4(3):290–295.
   PubMed Web of Science ®Google Scholar
• Zuber C, Mitteregger G, Pace C, Zerr I, Kretzschmar HA, Weiss S. Anti-LRP/LR antibody W3 hampers peripheral PrPSc propagation in scrapie infected mice. Prion. 2007;1(3):207–212.
   PubMed Web of Science ®Google Scholar
• Zuber C, Knackmuss S, Rey C, et al. Single chain Fv antibodies directed against the 37 kDa/67 kDa laminin receptor as therapeutic tools in prion diseases. Mol Immunol. 2008;45(1):144–151.
   PubMed Web of Science ®Google Scholar
• Du Y, Dodel R, Hampel H, et al. Reduced levels of amyloid beta-peptide antibody in Alzheimer disease. Neurology. 2001;57(5):801–805.
   PubMed Web of Science ®Google Scholar
• Weksler ME, Relkin N, Turkenich R, LaRusse S, Zhou L, Szabo P. Patients with Alzheimer disease have lower levels of serum anti-amyloid peptide antibodies than healthy elderly individuals. Exp Gerontol. 2002;37(7):943–948.
   PubMed Web of Science ®Google Scholar
• Dodel R, Hampel H, Depboylu C, et al. Human antibodies against amyloid beta peptide: a potential treatment for Alzheimer’s disease. Ann Neurol. 2002;52(2):253–256.
   Web of Science ®Google Scholar
• Dodel RC, Du Y, Depboylu C, et al. Intravenous immunoglobulins containing antibodies against beta-amyloid for the treatment of Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2004;75(10):1472–1474.
   PubMed Web of Science ®Google Scholar
• Du Y, Wei X, Dodel R, et al. Human anti-beta-amyloid antibodies block beta-amyloid fibril formation and prevent beta-amyloid-induced neurotoxicity. Brain. 2003;126(Pt 9):1935–1939.
   PubMedGoogle Scholar
• Wei X, Roettger Y, Tan B, et al. Human anti-prion antibodies block prion peptide fibril formation and neurotoxicity. J Biol Chem. 2012;287(16):12858–12866.
   Web of Science ®Google Scholar
• Dorban G, Defaweux V, Heinen E, Antoine N. Spreading of prions from the immune to the peripheral nervous system: a potential implication of dendritic cells. Histochem Cell Biol. 2010;133(5):493–504.
   Web of Science ®Google Scholar
• Dodel R, Balakrishnan K, Keyvani K, et al. Naturally occurring autoantibodies against beta-amyloid: investigating their role in transgenic animal and in vitro models of Alzheimer’s disease. J Neurosci. 2011;31(15):5847–5854.
   PubMed Web of Science ®Google Scholar
• Roettger Y, Zerr I, Dodel R, Bach JP. Prion peptide uptake in microglial cells – the effect of naturally occurring autoantibodies against prion protein. PLoS One. 2013;8(6):e67743.
   Web of Science ®Google Scholar
• Miyake K, Shimada T. . Development and Application of HIV Vectors Pseudotyped with HIV Envelopes. In: Ke Xu, editor. Viral Gene Therapy. 2011. Available from: http://www.intechopen.com/books/viral-gene-therapy/development-and-application-of-hiv-vectors-pseudotyped-with-hiv-envelopes. Accessed July 22, 2014.
   Google Scholar