Reducing AD-like pathology in 3xTg-AD mouse model by DNA epitope vaccine - A novel immunotherapeutic strategy

PLoS ONE

Volumn 3, Issue 5, 2008, Pages

  Movsesyan, Nina ^a,b   Ghochikyan, Anahit ^a   Mkrtichyan, Mikayel ^a   Petrushina, Irina ^b   Davtyan, Hayk ^a   Olkhanud, Purevdorj B ^c   Head, Elizabeth ^b,d   Biragyn, Arya ^c   Cribbs, David H ^b,d   Agadjanyan, Michael G ^a,b  

^a INSTITUTE FOR MOLECULAR MEDICINE   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c NATIONAL INSTITUTE ON AGING   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALZHEIMER DISEASE VACCINE; AMYLOID BETA PROTEIN ANTIBODY; AMYLOID BETA PROTEIN[1-42]; DNA EPITOPE VACCINE; EPITOPE; MACROPHAGE DERIVED CHEMOKINE; DNA VACCINE; MALARIA VACCINE; PADRE 45;

ALZHEIMER DISEASE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIBODY PRODUCTION; ANTIBODY RESPONSE; ANTIBODY TITER; ARTICLE; BRAIN HEMORRHAGE; CD4+ T LYMPHOCYTE; CELLULAR IMMUNITY; COGNITIVE DEFECT; CONTROLLED STUDY; DRUG EFFICACY; DRUG SAFETY; HUMORAL IMMUNITY; IMMUNOTHERAPY; INFLAMMATION; LYMPHOCYTIC INFILTRATION; MOUSE; NEUROPATHOLOGY; NONHUMAN; SPATIAL MEMORY; TH2 CELL; VACCINATION; ANIMAL; CLINICAL TRIAL; DISEASE MODEL; GENETICS; HUMAN; IMMUNOLOGY; METHODOLOGY; PATHOLOGY; T LYMPHOCYTE; TRANSGENIC MOUSE;

ANIMALIA; MUS;

ALZHEIMER DISEASE; ANIMALS; CLINICAL TRIALS AS TOPIC; DISEASE MODELS, ANIMAL; EPITOPES; HUMANS; IMMUNOTHERAPY; MALARIA VACCINES; MICE; MICE, TRANSGENIC; T-LYMPHOCYTES; VACCINES, DNA;

EID: 47749107621     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0002124     Document Type: Article

References (53)

1. Hardy JA, Higgins GA (1992) Alzheimer's disease: the amytoid cascade hypothesis. Science 256: 184-185.
2. Haass C, Selkoe DJ (2007) Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide. Nat Rev Mol Cell Biol 8: 101-112.
3. Schenk D, Barbour R, Dunn W, Gordon G, Grajeda H, et al. (1999) Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse [see comments]. Nature 400: 173-177.
4. Janus C, Pearson J, McLaurin J, Mathews PM, Jiang Y, et al. (2000) A beta peptide immunozation reduces behavioural impairment and plaques in a model of Alzheimer's disease. Nature 408: 979-982.
5. Morgan D, Diamond DM, Gottschall PE, Ugen KE, Dickey C, et al. (2000) A beta peptide vaccination prevents memory loss in an animal model of Alzheimer's disease. Nature 408: 982-985.
6. Dodart JC, Bales KR, Gannon KS, Greene SJ, DeMattos RB, et al. (2002) Immunization reverses memory deficits without reducing brain Abeta burden in Alzheimer's disease model. Nat Neurosci 5: 452-457.
7. Bard F, Cannon C, Barbour R, Burke RL, Games D, et al. (2000) Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nat Med 6: 916-919.
8. Hock C, Konietzko U, Streffer JR, Tracy J, Signorell A, et al. (2003) Antibodies against beta-Amyloid Slow Cognitive Decline in Alzheimer's Disease. Neuron 38: 547-554.
9. Ferrer I, Rovira MB, Guerra MLS, Rey MJ, Costa-Jussa F (2004) Neuropathology and pathogenesis of encephalitis following amyloid-beta immunization in Alzheimer's disease. Brain Pathol 14: 11-20.
10. Nicoll JA, Wilkinson D, Holmes C, Steart P, Markham H, et al. (2003) Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report. Nat Med 9: 448-452.
11. Orgogozo JM, Gilman S, Dartigues JM, Laurent B, Puel M, et al. (2003) Subacute meningoencephalitis in a subset of patients with AD after Abeta42 immunization. Neurology 61(1): 46-54.
12. Masliah E, Hansen L, Adame A, Crews L, Bard F, et al. (2005) Abeta vaccination effects on plaque pathology in the absence of encephalitis in Alzheimer disease. Neurology 64: 129-131.
13. Bayer AJ, Bullock R, Jones RW, Wilkinson D, Paterson KR, et al. (2005) Evaluation of the safety and immumigenicity of synthetic Abeta42 (AN 1792) in patients with AD. Neurology 64:94-101.
14. Patton RL, Kalback WM, Esh CL, Koljohn TA, Van Vickle GD, et al. (2006) Amyloid-beta peptide remnants in AN-1792-immunized Alzheimer's disease patients: a biochemical analysis. Am J Pathol 169: 1048-1063.
15. Nicoll JA, Barton E, Boche D, Neal JW, Ferrer I, et al. (2006) Abeta Species removal after abeta42 immunization. J Neuropathol Exp Neurol 65: 1040-1048.
16. Schenk D (2002) Opinion: Amyloid-beta immunotherapy for Alzheimer's disease: the end of the beginning. Nat Rev Neurosci 3: 824-828.
17. Cribbs DH, Agadjanyan MG (2005) Immunotherapy for Alzheimer's Disease: Potential Problems and Possible Solutions. Current Immunology Reviews 1: 139-155.
18. Lemere CA, Maier M, Jiang L, Peng Y, Seabrook TJ (2006) Amyloid-beta immunotherapy for the prevention and treatment of Alzheimer disease: lessons from mice, monkeys, and humans. Rejuvenation Res 9: 77-84.
19. Agadjanyan MG, Ghochikyan A, Petrushina I, Vasilevko V, Movsesyan N, et al. (2005) Prototype Alzheimer's disease vaccine using the immunodominant B Cell epitope from beta-amyloid and promiscuous T cell epitope pan HLA DR-binding peptide. J Immunol 174: 1580-1586.
20. Mamikonyan G, Necula M, Mkrtichyan M, Ghochikyan A, Petrushina I, et al. (2007) Anti-Abeta 1-11 antibody binds to different beta-amyloid species, inhibits fibril formation, and disaggregates preformed fibrils, bit not the most toxic oligomers. J Biol Chem 282: 22376-22386.
21. Petrushina I, Ghochikyan A, Mktrichyan M, Mamikonyan G, Movsesyan N, et al. (2007) Alzheimer's Disease Peptide Epitope Vaccine Reduces Insoluble But Not Soluble/Oligomeric A(beta) Species in Amyloid Precursor Protein Transgenic, Mice. J Neurosci 27: 12721-12731.
22. Alexander J, Sidney J, Southwood S, Ruppert J, Oseroff C, et al. (1994) Development of high potency universal DR-restricted helper epitopes by modification of high affinity DR-blocking peptides. Immunity 1: 751-761.
23. Ghochikyan A, Mkrtichyan M, Petrushina I, Movsesyan N, Karapetyan A, et al. (2006) Prototype Alzheimer's disease epitope vaccine induced strong Th2-type anti-Abeta antibody response with Alum to Quil A adjuvant switch. Vaccine 24: 2275-2282.
24. Ghochikyan A, Vasilevko V, Petrushína I, Tran M, Sadzikava N, et al. (2003) Generation and chracterization of the humoral immune response to DNA immunization with a chimeric β-amyloid-interleukin-4 minigene. Eur J Immunol 33: 3232-3241.
25. Qu B, Rosenberg RN, Li L, Boyer PJ, Johnston SA (2004) Gene vaccination to bias the immune response to amyloid-beta peptide as therapy for Alzheimer disease. Arch Neurol 61: 1859-1864.
26. Schultz JG, Salzer U, Mohajeri MH, Franke D, Heinrich J, et al. (2004) Antibodies from a DNA peptide vaccination decrease the brain amyloid burden in a mouse model of Alzheimer's disease. J Mol Med 82: 706-714.
27. Kutzler MA, Can C, Bai Y, Dong H, Choe PY, et al. (2006) Mapping of immune responses following wild-type and mutant ABeta42 plasmid or peptide vaccination in different mouse haplotypes and HLA Class II transgenic mice. Vaccine 24: 4630-4639.
28. Kim HD, Jin JJ, Maxwell JA, Fukuchi K (2007) Enhancing Th2 immune responses against amyloid protein by a DNA prime-adenovinis boost regimen for Alzheimer's disease. Immunol Lett 112: 30-38.
29. Biragyn A, Belyakov IM, Chow YH, Dimitrov DS, Berzofsky JA, et al. (2002) DNA vaccines encoding human immunodeficiency vinis-1 glycoprotein 120 fusions with proinflammatory chemoattractants induce systemic and mucosal immune responses. Blood 100: 1153-1159.
30. Biragyn A, Surerthu M, Yang D, Ruffini PA, Haines BA, et al. (2001) Mediators of innate immunity that target immature, but not mature, dendritic cells induce antitumor immunity when genetically fused with nonimmunogenic tumor antigens. J Immunol 167: 6644-6653.
31. Monsonego A, Maron R, Zota V, Selkoe DJ, Weiner HL (2001) Immune hyporespobnsivness to amyloid b-peptide in amyloid precursor protein transgenic: mice: mplications for the pathogenesis and treatment of Alzheimer's disease. Proc Nat Acad Sci, USA, 98: 10273-10278.
32. Petrushina I, Tran M, Sadzikava N, Ghochikyan A, Vasilevko V, et al. (2003) Importance of IgG2c isotype in the immune response to b-amyloid in APP/Tg mice. Neurosci Letters 338: 5-8.
33. Li Q Gordon M, Cao C, Ugen KE, Morgan D (2007) Improvement of a low pH antigen-antibody dissociation procedure for ELISA measurement of circulating anti-Abeta antibodies. BMG Neurosci 8: 22.
34. Pasquali JL, Soulas-Sprauel P, Korganow AS, Martin T (2007) Auto-reactive B cells in transgenic, mice. J Autoimmun 29: 250-256.
35. Snapper CM, Paul WE (1987) Interferon-gamma and B cell stimulatory factor-1 reciprocally regulate Ig isotype production. Science 236: 944-947.
36. Billings LM, Oddo S, Green KN, McGaugh JL, Laferla FM (2005) Intraneuronal Abeta causes the onset of early Alzheimer's disease-related cognitive deficits in transgcnic mice. Neuron 45: 675-688.
37. Ballatore C, Lee VM, Trojanowski JQ (2007) Tau-mediated neurodegeneration in Alzheimer's disease and related disorders. Nat Rev Neurosci 8: 663-672.
38. Lewis J, Dickson DW, Lin W-L, Chisholm L, Corral A, et al. (2001) Enhanced Neurofibrillary Degeneration in Transgenic Mice Expressing Mutant Tau and APP. Science 293: 1487-1491.
39. Oddo S, Caccamo A, Kitazawa M, Tseng BP, LaFerla FM (2003) Amyloid deposition precedes tangle formation in a triple transgenic model of Alzheimer's disease. Neurobiol Aging 24: 1063-1070.
40. Oddo S, Vasilevko V, Caccamo A, Kitazawa M, Cribbs DH, et al. (2006) Reduction of soluble Abeta and tau, but not soluble Abets alone, ameliorates cognitive decline in transgenic mice with plaques and tangles. J Biol Chem.
41. Pfeifer M, Boncristiano S, Bondolfi L, Stalder A, Deller T, et al. (2002) Cerebral hemorrhage after passive anti-Abeta immunotherapy. Science 298: 1379.
42. Wilcock DM, Jantzen PT, Li Q Morgan D, Gordon MN (2007) Amyloid-b vaccination, but not nitro-NSAID treatment, increases vascular amyloid and microhemorrhage while both reduce parenchymal amyloid. Neuroscience, in press.
43. Chen G, Chen KS, Kobayashi D, Barbour R. Motter R, et al. (2007) Active beta-amyloid immunization restores spatial learning in PDAPP mice displaying very low levels of beta-amyloid. J Neurosci 27: 2654-2662.
44. Bonecchi R, Bianchi G, Bordignon PP, D'Ambrosio D, Lang R, et al. (1998) Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s. J Exp Med 187: 129-134.
45. Sallusto F, Lenig D, Mackay CR, Lanzavecchia A (1998) Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes. J Exp Med 187: 875-883.
46. Imai T, Nagira M, Takagi S, Kakizald M, Nishimura M, et al. (1999) Selective recruitment of CCR4-bearing Th2 cells toward antigen-presenting cells by the CC chemokines thymus and activation-regulated chemokine and macrophage-derived chemokine. Int Immunol 11: 81-88.
47. Zaliauskiene L, Kang S, Sparks K, Zinn KR, Schwiebert LM, et al. (2002) Enhancement of MHC class II-restricted responses by receptor-mediated uptake of peptide antigens. J Immunol 169: 2337-2345.
48. Biragyn A, Ruffini PA, Coscia M, Harvey LK, Neelapu SS, et al. (2004) Chemokine receptor-mediated delivery directs self-tumor antigen efficiently into the class II processing pathway in vitro and induces protective immunity in vivo. Blood 104: 1961-1969.
49. Schiavo R, Baatar D, Olkhanud P, Indig FE, Restifo N, et al. (2006) Chemokine receptor targeting efficiently directs antigens to MHC class I pathways and elicits antigen-specific CD8+ T-cell responses. Blood 107: 4597-4605.
50. Berzofsky JA, Ahlers JD, Belyakov IM (2001) Strategies for designing and optimizing new generation vaccines. Nature Rev Immunol 1: 209-219.
51. Okura Y, Miyakoshi A, Kohyama Y, Park IK, Staufenbiel M, et al. (2006) Nonviral Abeta DNA vaccine therapy against Alzheimer's disease: long-term effects and safety. Proc Natl Acad Sci U S A 103: 9619-9624.
52. Monsonego A, Zota V, Karni A, Krieger JI, Bar-Or A, et al. (2003) Increased T cell reactivity to amyloid beta protein in older humans and patients with Alzheimer disease. J Clin Invest 112(3): 415-422.
53. Cribbs DH, Ghochikyan A, Tran M, Vasilevko V, Petrushina I, et al. (2003) Adjuvant-dependent modulation of Th1 and Th2 responses to immunization with beta-amyloid. Int Immunol 15:505-514.