Strikingly reduced amyloid burden and improved behavioral performance in Alzheimer's disease mice immunized with recombinant chimeric vaccines by hexavalent foldable Aβ1-15 fused to toxin-derived carrier proteins

Journal of Alzheimer's Disease

Volumn 41, Issue 1, 2014, Pages 243-260

  Yu, Yun Zhou ^a   Wang, Wen Bin ^a   Chen, Ao ^a,b   Chang, Qing ^a   Liu, Si ^a   Zhao, Meng ^a,c   Wang, Shuang ^a   Qiu, Wei Yi ^a   Pang, Xiao Bin ^b   Xu, Qing ^c   Sun, Zhi Wei ^a  

^a BEIJING INSTITUTE OF BIOTECHNOLOGY   (China)

^b HENAN UNIVERSITY   (China)

^c BEIJING JIAOTONG UNIVERSITY   (China)

Author keywords

Alzheimer's disease; carrier protein; chimeric vaccines; immunotherapy; molecular adjuvant

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID BETA PROTEIN[1-15]; CARRIER PROTEIN; CHIMERIC PROTEIN; EPITOPE; PAN HLA DR BINDING PEPTIDE; PLASMID VECTOR; TOXIN; UNCLASSIFIED DRUG; ALZHEIMER DISEASE VACCINE; AMYLOID BETA-PROTEIN (1-15); AMYLOID BETA-PROTEIN (1-42); ANTIBODY; BOTULINUM TOXIN A; IMMUNOTOXIN; MALARIA VACCINE; PADRE 45; PEPTIDE FRAGMENT; RECOMBINANT VACCINE; SUBUNIT VACCINE;

ALZHEIMER DISEASE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIBODY RESPONSE; ANTIBODY TITER; ARTICLE; CELLULAR IMMUNITY; CONTROLLED STUDY; FEMALE; IMMUNE RESPONSE; MEMORY CELL; MOUSE; NONHUMAN; PRIORITY JOURNAL; SPATIAL MEMORY; AGING; ANIMAL; BAGG ALBINO MOUSE; BRAIN; C57BL MOUSE; DISEASE MODEL; ESCHERICHIA COLI; GENETICS; IMMUNOLOGY; METABOLISM; PATHOLOGY; PHYSIOLOGY; PLAQUE, AMYLOID; RANDOMIZATION; T LYMPHOCYTE; TRANSGENIC MOUSE; VACCINATION;

AGING; ALZHEIMER DISEASE; ALZHEIMER VACCINES; AMYLOID BETA-PEPTIDES; ANIMALS; ANTIBODIES; BOTULINUM TOXINS, TYPE A; BRAIN; DISEASE MODELS, ANIMAL; ESCHERICHIA COLI; IMMUNOTOXINS; MALARIA VACCINES; MICE, INBRED BALB C; MICE, INBRED C57BL; MICE, TRANSGENIC; PEPTIDE FRAGMENTS; PLAQUE, AMYLOID; RANDOM ALLOCATION; SPATIAL MEMORY; T-LYMPHOCYTES; VACCINATION; VACCINES, SUBUNIT; VACCINES, SYNTHETIC;

EID: 84902243278     PISSN: 13872877     EISSN: 18758908     Source Type: Journal    
DOI: 10.3233/JAD-132177     Document Type: Article

References (49)

1. Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics. Science 297, 353-356.
2. Pimplikar SW (2009) Reassessing the amyloid cascade hypothesis of Alzheimer's disease. Int J Biochem Cell Biol 41, 1261-1268.
3. 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.
4. Ghochikyan A (2009) Rationale for peptide and DNA based epitope vaccines for Alzheimer's disease immunotherapy. CNS Neurol Disord Drug Targets 8, 128-143.
5. Lemere CA, Masliah E (2010) Can Alzheimer disease be prevented by amyloid-beta immunotherapy? Nat Rev Neurol 6, 108-119.
6. Orgogozo JM, Gilman S, Dartigues JF, Laurent B, Puel M, Kirby LC, Jouanny P, Dubois B, Eisner L, Flitman S, Michel BF, Boada M, Frank A, Hock C (2003) Subacute menin-goencephalitis in a subset of patients with AD after Abeta42 immunization. Neurology 61, 46-54.
7. Cribbs DH, Ghochikyan A, Vasilevko V, Tran M, Petrushina I, Sadzikava N, Babikyan D, Kesslak P, Kieber-Emmons T, Cotman CW, Agadjanyan MG (2003) Adjuvant-dependent modulation of Th1 and Th2 responses to immunization with beta-amyloid. Int Immunol 15, 505-514.
8. Shah S, Federoff HJ (2011) Therapeutic potential of vaccines for Alzheimer's disease. Immunotherapy 3, 287-298.
9. Agadjanyan MG, Ghochikyan A, Petrushina I, Vasilevko V, Movsesyan N, Mkrtichyan M, Saing T, Cribbs DH (2005) Prototype Alzheimer's disease vaccine using the immun-odominantBcell epitope from beta-amyloid and promiscuous T cell epitope pan HLA DR-binding peptide. J Immunol 174, 1580-1586.
10. Mamikonyan G, Necula M, Mkrtichyan M, Ghochikyan A, Petrushina I, Movsesyan N, Mina E, Kiyatkin A, Glabe CG, Cribbs DH, Agadjanyan MG (2007) Anti-A beta 1-11 antibody binds to different beta-amyloid species, inhibits fibril formation, and disaggregates preformed fibrils but not the most toxic oligomers. J Biol Chem 282, 22376-22386.
11. Petrushina I, Ghochikyan A, Mktrichyan M, Mamikonyan G, Movsesyan N, Davtyan H, Patel A, Head E, Cribbs DH, Agadjanyan MG (2007) Alzheimer's disease peptide epitope vaccine reduces insoluble but not soluble/oligomeric Abeta species in amyloid precursor protein transgenic mice. J Neu-rosci 27, 12721-12731.
12. Movsesyan N, Mkrtichyan M, Petrushina I, Ross TM, Cribbs DH, Agadjanyan MG, Ghochikyan A (2008) DNA epitope vaccine containing complement component C3d enhances anti-amyloid-beta antibody production and polarizes the immune response towards a Th2 phenotype. J Neuroimmunol 205, 57-63.
13. Movsesyan N, Ghochikyan A, Mkrtichyan M, Petrushina I, Davtyan H, Olkhanud PB, Head E, Biragyn A, Cribbs DH, Agadjanyan MG (2008) Reducing AD-like pathology in 3xTg-AD mouse model by DNA epitope vaccine-a novel immunotherapeutic strategy. PLoS One 3, e2124.
14. Moretto N, Bolchi A, Rivetti C, Imbimbo BP, Villetti G, Pietrini V, Polonelli L, Del Signore S, Smith KM, Ferrante RJ, Ottonello S (2007) Conformation-sensitive antibodies against alzheimer amyloid-beta by immunization with a thioredoxin-constrained B-cell epitope peptide. J Biol Chem 282, 11436-11445.
15. Zou J, Yao Z, Zhang G, Wang H, Xu J, Yew DT, Forster EL (2008) Vaccination of Alzheimer's model mice with aden-ovirus vector containing quadrivalent foldable Abeta (1-15) reduces Abeta burden and behavioral impairment without Abeta-specific T cell response. J Neurol Sci 272, 87-98.
16. Chackerian B (2010) Virus-like particle based vaccines for Alzheimer disease. Hum Vaccin 6, 926-930.
17. Wiessner C, Wiederhold KH, Tissot AC, Frey P, Danner S, Jacobson LH, Jennings GT, Luond R, Ortmann R, Reich-wald J, Zurini M, Mir A, Bachmann MF, Staufenbiel M (2011) The second-generation active Abeta immunotherapy CAD106 reduces amyloid accumulation in APP transgenic mice while minimizing potential side effects. J Neurosci 31, 9323-9331.
18. Olkhanud PB, Mughal M, Ayukawa K, Malchinkhuu E, Bodogai M, Feldman N, Rothman S, Lee JH, Chigurupati S, Okun E, Nagashima K, Mattson MP, Biragyn A (2012) DNA immunization with HBsAg-based particles expressingaBcell epitope of amyloid beta-peptide attenuates disease progression and prolongs survival in a mouse model of Alzheimer's disease. Vaccine 30, 1650-1658.
19. Davtyan H, Ghochikyan A, Cadagan R, Zamarin D, Petrushina I, Movsesyan N, Martinez-Sobrido L, Albrecht RA, Garcia-Sastre A, Agadjanyan MG (2011) The immuno-logical potency and therapeutic potential of a prototype dual vaccine against influenza and Alzheimer's disease. J Transl Med 9, 127.
20. Yu YZ, Wang S, Bai JY, Zhao M, Chao A, Wang WB, Chang Q, Liu S, Wei-Yi Qiu WY, Pang XB, Xu Q, Sun ZW (2013) Effective DNA epitope chimeric vaccines for Alzheimer's disease using a toxin-derived carrier protein as a molecular adjuvant. Clin Immunol 149, 11-24.
21. Yu YZ, Li N, Zhu HQ, Wang RL, Du Y, Wang S, Yu WY, Sun ZW (2009) The recombinant Hc subunit of Clostrid-ium botulinum neurotoxin serotype A is an effective botulism vaccine candidate. Vaccine 27, 2816-2822.
22. Yu YZ, Gong ZW, Ma Y, Zhang SM, Zhu HQ, Wang WB, Du Y, Wang S, Yu WY, Sun ZW (2011) Co-expression of tetanus toxin fragment C in Escherichia coli with thioredoxin and its evaluation as an effective subunit vaccine candidate. Vaccine 29, 5978-5985.
23. Zhang J, Wu X, Qin C, Qi J, Ma S, Zhang H, Kong Q, Chen D, Ba D, He W (2003) A novel recombinant adeno-associated virus vaccine reduces behavioral impairment and beta-amyloid plaques in a mouse model of Alzheimer's disease. Neurobiol Dis 14, 365-379.
24. Alexander J, Fikes J, Hoffman S, Franke E, Sacci J, Appella E, Chisari FV, Guidotti LG, Chesnut RW, Livingston B, Sette A (1998) The optimization of helper T lymphocyte (HTL) function in vaccine development. Immunol Res 18, 79-92.
25. Simpson LL, Maksymowych AB, Kiyatkin N (1999) Botulinum toxin as a carrier for oral vaccines. Cell Mol Life Sci 56, 47-61.
26. Diethelm-Okita BM, Okita DK, Banaszak L, Conti-Fine BM (2000) Universal epitopes for human CD4+ cells on tetanus and diphtheria toxins. J Infect Dis 181, 1001-1009.
27. Baraldo K, Mori E, Bartoloni A, Petracca R, Giannozzi A, Norelli F, Rappuoli R, Grandi G, Del Giudice G (2004) N19 polyepitope as a carrier for enhanced immunogenicity and protective efficacy of meningococcal conjugate vaccines. Infect Immun 72, 4884-4887.
28. Monsonego A, Maron R, Zota V, Selkoe DJ, Weiner HL (2001) Immune hyporesponsiveness to amyloid beta-peptide in amyloid precursor protein transgenic mice: Implications for the pathogenesis and treatment of Alzheimer's disease. Proc Natl Acad Sci USA 98, 10273-10278.
29. Wisniewski T, Sigurdsson EM (2010) Murine models of Alzheimer's disease and their use in developing immunotherapies. Biochim Biophys Acta 1802, 847-859.
30. Wisniewski T, Boutajangout A (2010) Immunotherapeutic approaches for Alzheimer's disease in transgenic mouse models. Brain Struct Funct 214, 201-218.
31. Bayer AJ, Bullock R, Jones RW, Wilkinson D, Paterson KR, Jenkins L, Millais SB, Donoghue S (2005) Evaluation of the safety and immunogenicity of synthetic Abeta42 (AN1792) in patients with AD. Neurology 64, 94-101.
32. Gilman S, Koller M, Black RS, Jenkins L, Griffith SG, Fox NC, Eisner L, Kirby L, Rovira MB, Forette F, Orgogozo JM (2005) Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology 64, 1553-1562.
33. Delrieu J, Ousset PJ, Caillaud C, Vellas B (2012) 'Clinical trials in Alzheimer's disease': Immunotherapy approaches. J Neurochem 120 (Suppl 1), 186-193.
34. Cribbs DH (2010) Abeta DNA vaccination for Alzheimer's disease: Focus on disease prevention. CNS Neurol Disord Drug Targets 9, 207-216.
35. Patton RL, Kalback WM, Esh CL, Kokjohn TA, Van Vickle GD, Luehrs DC, Kuo YM, Lopez J, Bruno D, Ferrer I, Masliah E, Newel AJ, Beach TG, Castano EM, Roher AE (2006) Amyloid-beta peptide remnants in AN-1792-immunized Alzheimer's disease patients-A biochemical analysis. Am J Pathol 169, 1048-1063.
36. Mastrangelo MA, Sudol KL, Narrow WC, Bowers WJ (2009) Interferon-)/differentially affects Alzheimer' s disease pathologies and induces neurogenesis in triple transgenic-AD mice. Am J Pathol 175, 2076-2088.
37. Walter J, Honsek SD, Illes S, Wellen JM, Hartung HP, Rose CR, Dihne M (2011) A new role for interferon gamma in neural stem/precursor cell dysregulation. Mol Neurodegener 6, 18.
38. Browne TC, McQuillan K, McManus RM, O'Reilly JA, Mills KH, Lynch MA (2013) IFN-y Production by amyloid fj-specific Th1 cells promotes microglial activation and increases plaque burden in a mouse model of Alzheimer's disease. J Immunol 190, 2241-2251.
39. Menendez-Gonzalez M, Perez-Pinera P, Martinez-Rivera M, Muniz AL, Vega JA (2011) Immunotherapy for Alzheimer's disease: Rational basis in ongoing clinical trials. Curr Pharm Des 17, 508-520.
40. Wisniewski T, Boutajangout A (2010) Vaccination as a therapeutic approach to Alzheimer's Disease. Mt Sinai J Med 77, 17-31.
41. Venkitaramani DV, Chin J, Netzer WJ, Gouras GK, Lesne S, Malinow R, Lombroso PJ (2007) Beta-amyloid modulation of synaptic transmission and plasticity. J Neurosci 27, 11832-11837.
42. Selkoe DJ (2008) Soluble oligomers of the amyloid beta-protein impair synaptic plasticity and behavior. Behav Brain Res 192, 106-113.
43. Jacobsen JS, Wu CC, Redwine JM, Comery TA, Arias R, Bowlby M, Martone R, Morrison JH, Pangalos MN, Reinhart PH, Bloom FE (2006) Early-onset behavioral and synaptic deficits in a mouse model of Alzheimer's disease. Proc Natl Acad Sci USA 103, 5161-5166.
44. Nabar NR, Yuan F, Lin X, Wang L, Bai G, Mayl J, Li Y, Zhou SF, Wang J, Cai J, Cao C (2012) Cell Therapy: A safe and efficacious therapeutic treatment for Alzheimer's Disease in APP+PS1 mice. PLoS One 7, e49468.
45. Chen GQ, Chen KS, Kobayashi D, Barbour R, Motter R, Games D, Martin SJ, Morris RGM (2007) Active beta-amyloid immunization restores spatial learning in PDAPP mice displaying very low levels of beta-amyloid. J Neurosci 27, 2654-2662.
46. Movsesyan N, Davtyan H, Mkrtichyan M, Petrushina I, Tiraturyan T, Ross T, Agadjanyan MG, Ghochikyan A, Cribbs DH (2010) Low concentrations of Anti-Afj antibodies generated in Tg2576 mice by DNA epitope vaccine fused with 3C3d molecular adjuvant do not affect AD pathology. Hum GeneTher 21, 1569-1576.
47. Pasquali JL, Soulas-Sprauel P, Korganow AS, Martin T (2007) Auto-reactive B cells in transgenic mice. J Autoimmun 29, 250-256.
48. Savelyeva N, King CA, Vitetta ES, Stevenson FK (2005) Inhibition of a vaccine-induced anti-tumor B cell response by soluble protein antigen in the absence of continuing T cell help. Proc Natl Acad Sci USA 102, 10987-10992.
49. Keitel WA, Kester KE, Atmar RL, White AC, Bond NH, Holland CA, Krzych U, Palmer DR, Egan A, Diggs C, Ballou WR, Hall BF, Kaslow D (1999) Phase I trial of two recombinant vaccines containing the 19kd carboxy terminal fragment of Plasmodium falciparum merozoite surface protein 1 (msp-1 (19)) and T helper epitopes of tetanus toxoid. Vaccine 18, 531-539.