Immunogenicity of DNA- and recombinant protein-based Alzheimer disease epitope vaccines

Human Vaccines and Immunotherapeutics

Volumn 10, Issue 5, 2014, Pages 1248-1255

  Davtyan, Hayk ^a   Bacon, Andrew ^b   Petrushina, Irina ^c   Zagorski, Karen ^a   Cribbs, David H ^c   Ghochikyan, Anahit ^a   Agadjanyan, Michael G ^a,c  

^a INSTITUTE FOR MOLECULAR MEDICINE   (United States)

^b Xenetic Biosciences   (United Kingdom)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Adjuvants; Alzheimer disease; DNA vaccine; Electroporation; Immune responses; Liposome based vaccination; Protein vaccine

Indexed keywords

ACI 24; AD 02; AD 03; ALZHEIMER DISEASE VACCINE; AV 1955D; AV 1959D; AV 1982R; BAPINEUZUMAB; CAD 106; DNA VACCINE; GANTENERUMAB; IMMUNOLOGICAL ADJUVANT; LIPOSOME; PLACEBO; RECOMBINANT PROTEIN; SOLANEZUMAB; UB 311; UNCLASSIFIED DRUG; V 950; VANUTIDE CRIDIFICAR; EPITOPE;

ACTIVE IMMUNIZATION; ALZHEIMER DISEASE; ANTIBODY PRODUCTION; ANTIBODY RESPONSE; ANTIBODY TITER; DRUG EFFICACY; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; ELECTROPORATION; HUMAN; IMMUNOGENICITY; NONHUMAN; NOTE; PASSIVE IMMUNIZATION; ANIMAL; DRUG EFFECTS; GENETICS; IMMUNOGENETICS; IMMUNOLOGY;

ALZHEIMER DISEASE; ALZHEIMER VACCINES; ANIMALS; EPITOPES; HUMANS; IMMUNOGENETIC PHENOMENA; RECOMBINANT PROTEINS; VACCINES, DNA;

EID: 84901432028     PISSN: 21645515     EISSN: 2164554X     Source Type: Journal    
DOI: 10.4161/hv.27882     Document Type: Note

References (63)

1. Dementia WHO. key facts. http://www.who.int/mediacentre/factsheets/fs362/ en/, 2012.
2. Price DL, Sisodia SS. Cellular and molecular biology of Alzheimer's disease and animal models. Annu Rev Med 1994; 45:435-46; PMID:8198393; http://dx.doi.org/10.1146/annurev.med.45.1.435
3. Selkoe DJ. The molecular pathology of Alzheimer's disease. Neuron 1991; 6:487-98; PMID:1673054; http://dx.doi.org/10.1016/0896-6273(91)90052-2
4. Selkoe DJ. Alzheimer's disease: a central role for amyloid. J Neuropathol Exp Neurol 1994; 53:438-47; PMID:8083687; http://dx.doi.org/10.1097/00005072- 199409000-00003
5. Esler WP, Wolfe MS. A portrait of Alzheimer secretases - new features and familiar faces. Science 2001; 293:1449-54; PMID:11520976; http://dx.doi.org/10. 1126/science.1064638
6. Orgogozo JM, Gilman S, Dartigues JF, Laurent B, Puel M, Kirby LC, Jouanny P, Dubois B, Eisner L, Flitman S, et al. Subacute meningoencephalitis in a subset of patients with AD after Abeta42 immunization. Neurology 2003; 61:46-54; PMID:12847155; http://dx.doi.org/10.1212/01.WNL.0000073623.84147.A8
7. Imbimbo BP, Ottonello S, Frisardi V, Solfrizzi V, Greco A, Seripa D, Pilotto A, Panza F. Solanezumab for the treatment of mild-to-moderate Alzheimer's disease. Expert Rev Clin Immunol 2012; 8:135-49; PMID:22288451; http://dx.doi.org/10.1586/eci.11.93
8. Kerchner GA, Boxer AL. Bapineuzumab. Expert Opin Biol Ther 2010; 10:1121-30; PMID:20497044; http://dx.doi.org/10.1517/14712598.2010.493872
9. Delrieu J, Ousset PJ, Vellas B. Gantenerumab for the treatment of Alzheimer's disease. Expert Opin Biol Ther 2012; 12:1077-86; PMID:22583155; http://dx.doi.org/10.1517/14712598.2012.688022
10. Lemere CA. Immunotherapy for Alzheimer's disease: hoops and hurdles. Mol Neurodegener 2013; 8:36; PMID:24148220; http://dx.doi.org/10.1186/1750-1326-8-36
11. Eli Lilly and Company Announcment. Eli Lilly and Company Announces Top-Line Results on Solanezumab Phase 3 Clinical Trials in Patients with Alzheimer's Disease. Available at http://newsroom.lilly.com/releasedetail.cfm? releaseid=702211, 2012.
12. Sperling R, Salloway S, Raskind MA, Ferris S, Liu E, Yuen E, et al. A randomized double-blind, placebocontrolled clinical trila of intravenous bapineuzumab in patients with Alzheimer's disease who are apolipoprotein E ε4 carriers. 16th Congress of the European Federation of Neurological Societies. Stokholm, Sweden, 2012.
13. Salloway S, Sperling R, Honig L, Porsteinsson A, Sabbagh M, Liu E, et al. A randomized double-blind, placebocontrolled clinical trila of intravenous bapineuzumab in patients with Alzheimer's disease who are apolipoprotein E ε4 non-carriers. 16th Congress of the European Federation of Neurological Societies. Stokholm, Sweden, 2012.
14. Farlow M, Arnold SE, van Dyck CH, Aisen PS, Snider BJ, Porsteinsson AP, Friedrich S, Dean RA, Gonzales C, Sethuraman G, et al. Safety and biomarker effects of solanezumab in patients with Alzheimer's disease. Alzheimers Dement 2012; 8:261-71; PMID:22672770; http://dx.doi.org/10.1016/j.jalz.2011.09.224
15. NIH. Gantenerumab for Prodromal Alzheimer's Disease. http://www.nia.nih. gov/alzheimers/clinical-trials/gantenerumab-prodromal-alzheimers-disease.
16. NIH. Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia. A Study of Potential Disease Modifying Treatments in Individuals at Risk for or With a Type of Early Onset Alzheimer's Disease Caused by a Genetic Mutation. (DIAN TU). http://clinicaltrials.gov/ct2/show/ NCT01760005.
17. NIH. NIH-supported Alzheimer's studies to focus on innovative treatments. http://www.nih.gov/news/health/jan2013/nia-14.htm. 2013.
18. Agadjanyan MG, Ghochikyan A, Petrushina I, Vasilevko V, Movsesyan N, Mkrtichyan M, Saing T, Cribbs DH. 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 2005; 174:1580-6; PMID:15661919
19. Ghochikyan A, Mkrtichyan M, Petrushina I, Movsesyan N, Karapetyan A, Cribbs DH, Agadjanyan MG. Prototype Alzheimer's disease epitope vaccine induced strong Th2-type anti-Abeta antibody response with Alum to Quil A adjuvant switch. Vaccine 2006; 24:2275-82; PMID:16368167; http://dx.doi.org/10.1016/j. vaccine.2005.11.039
20. Davtyan H, Mkrtichyan M, Movsesyan N, Petrushina I, Mamikonyan G, Cribbs DH, Agadjanyan MG, Ghochikyan A. DNA prime-protein boost increased the titer, avidity and persistence of anti-Abeta antibodies in wild-type mice. Gene Ther 2010; 17:261-71; PMID:19865176; http://dx.doi.org/10.1038/gt.2009.140
21. Davtyan H, Ghochikyan A, Petrushina I, Hovakimyan A, Davtyan A, Poghosyan A, Marleau AM, Movsesyan N, Kiyatkin A, Rasool S, et al. Immunogenicity, efficacy, safety, and mechanism of action of epitope vaccine (Lu AF20513) for Alzheimer's disease: prelude to a clinical trial. J Neurosci 2013; 33:4923-34; PMID:23486963; http://dx.doi.org/10.1523/JNEUROSCI.4672-12.2013
22. Petrushina I, Ghochikyan A, Mktrichyan M, Mamikonyan G, Movsesyan N, Davtyan H, Patel A, Head E, Cribbs DH, Agadjanyan MG. Alzheimer's disease peptide epitope vaccine reduces insoluble but not soluble/oligomeric Abeta species in amyloid precursor protein transgenic mice. J Neurosci 2007; 27:12721-31; PMID:18003852; http://dx.doi.org/10.1523/JNEUROSCI.3201-07.2007
23. Delrieu J, Ousset PJ, Caillaud C, Vellas B. 'Clinical trials in Alzheimer's disease': immunotherapy approaches. J Neurochem 2012; 120(Suppl 1):186-93; PMID:21883222; http://dx.doi.org/10.1111/j.1471-4159.2011.07458.x
24. Lobello K, Ryan JM, Liu E, Rippon G, Black R. Targeting Beta amyloid: a clinical review of immunotherapeutic approaches in Alzheimer's disease. Int J Alzheimers Dis 2012; 2012:628070; PMID:22292124; http://dx.doi.org/10.1155/2012/ 628070
25. Lemere CA, Masliah E. Can Alzheimer disease be prevented by amyloid-beta immunotherapy? Nat Rev Neurol 2010; 6:108-19; PMID:20140000; http://dx.doi.org/10.1038/nrneurol.2009.219
26. Hickman DT, López-Deber MP, Ndao DM, Silva AB, Nand D, Pihlgren M, Giriens V, Madani R, St-Pierre A, Karastaneva H, et al. Sequence-independent control of peptide conformation in liposomal vaccines for targeting protein misfolding diseases. J Biol Chem 2011; 286:13966-76; PMID:21343310; http://dx.doi.org/10.1074/jbc.M110.186338
27. Muhs A, Hickman DT, Pihlgren M, Chuard N, Giriens V, Meerschman C, van der Auwera I, van Leuven F, Sugawara M, Weingertner MC, et al. Liposomal vaccines with conformation-specific amyloid peptide antigens define immune response and efficacy in APP transgenic mice. Proc Natl Acad Sci U S A 2007; 104:9810-5; PMID:17517595; http://dx.doi.org/10.1073/pnas.0703137104
28. Goodman JLUS. Food and Drug Administration Workshop: Adjuvants and Adjuvanted Preventive and Therapeutic Vaccines for Infectious Disease Indications 2008. Available from: http://www.fda.gov/downloads/ BiologicsBloodVaccines/NewsEvents/WorkshopsMeetingsConferences/UCM095732.pdf
29. Baylor NW, Egan W, Richman P. Aluminum salts in vaccines - US perspective. Vaccine 2002; 20(Suppl 3):S18-23; PMID:12184360; http://dx.doi.org/10.1016/S0264-410X(02)00166-4
30. Rappuoli R, Mandl CW, Black S, De Gregorio E. Vaccines for the twenty-first century society. Nat Rev Immunol 2011; 11:865-72; PMID:22051890
31. Galimberti D, Ghezzi L, Scarpini E. Immunotherapy against amyloid pathology in Alzheimer's disease. J Neurol Sci 2013; 333:50-4; PMID:23299047; http://dx.doi.org/10.1016/j.jns.2012.12.013
32. Winblad B, Andreasen N, Minthon L, Floesser A, Imbert G, Dumortier T, Maguire RP, Blennow K, Lundmark J, Staufenbiel M, et al. Safety, tolerability, and antibody response of active Aβ immunotherapy with CAD106 in patients with Alzheimer's disease: randomised, double-blind, placebo-controlled, first-in-human study. Lancet Neurol 2012; 11:597-604; PMID:22677258; http://dx.doi.org/10.1016/S1474-4422(12)70140-0
33. Schneeberger A, Mandler M, Mattner F, Schmidt W. AFFITOME® technology in neurodegenerative diseases: the doubling advantage. Hum Vaccin 2010; 6:948-52; PMID:20980801; http://dx.doi.org/10.4161/hv.6.11.13217
34. International WHO. Clinical Trials. In: GmbH NP, ed., http://apps.who.int/trialsearch/trial.aspx?trialid=EUCTR2009-012394-35-DE, 2010.
35. Genetic Engineering and Biotechnology News. AFFiRiS Invests in Public-Funded Lab to Develop Vaccine Against Diabetes and Cardiometabolic Diseases. http://www.genengnews.com/keywordsandtools/print/4/23255/.
36. NIH. Study to Evaluate Safety, Tolerability and Immunogenicity of Vaccine (UB 311) in Subjects With Alzheimer's Disease. http://clinicaltrials.gov/ct2/ show/NCT00965588.
37. Savage MJ, Wu GY, McCampbell A, Wessner KR, Citron M, Liang X, et al. A novel multivalent Abeta peptide vaccine with preclinical evidence of a central immune response that generates antisera recognizing a wide range of abeta peptide species. Alzheimers Dement 2010; 6:S142; http://dx.doi.org/10.1016/j. jalz.2010.05.437
38. Davtyan H, Ghochikyan A, Petrushina I, Hovakimyan A, Davtyan A, Cribbs DH, Agadjanyan MG. The MultiTEP platform-based Alzheimer's disease epitope vaccine activates a broad repertoire of T helper cells in nonhuman primates. Alzheimers Dement 2014; (Forthcoming); PMID:24560029; http://dx.doi.org/10.1016/ j.jalz.2013.12.003
39. H. Lundbeck A/S. Lundbeck and Otsuka to co-develop a vaccine, Lu AF20513, their third collaborative development project to tackle Alzheimer's disease. http://investor.lundbeck.com/releasedetail.cfm?ReleaseID=813105. 2013.
40. Mura T, Proust-Lima C, Jacqmin-Gadda H, Akbaraly TN, Touchon J, Dubois B, Berr C. Measuring cognitive change in subjects with prodromal Alzheimer's disease. J Neurol Neurosurg Psychiatry 2013; (Forthcoming); PMID:23840054
41. Babiuk LA, Pontarollo R, Babiuk S, Loehr B, van Drunen Littel-van den Hurk S. Induction of immune responses by DNA vaccines in large animals. Vaccine 2003; 21:649-58; PMID:12531334; http://dx.doi.org/10.1016/S0264-410X(02)00574-1
42. Li L, Saade F, Petrovsky N. The future of human DNA vaccines. J Biotechnol 2012; 162:171-82; PMID:22981627; http://dx.doi.org/10.1016/j.jbiotec. 2012.08.012
43. Ferraro B, Morrow MP, Hutnick NA, Shin TH, Lucke CE, Weiner DB. Clinical applications of DNA vaccines: current progress. Clin Infect Dis 2011; 53:296-302; PMID:21765081; http://dx.doi.org/10.1093/cid/cir334
44. Gregersen JP. DNA vaccines. Naturwissenschaften 2001; 88:504-13; PMID:11824223; http://dx.doi.org/10.1007/s00114-001-0270-2
45. Ghochikyan A, Vasilevko V, Petrushina I, Movsesyan N, Babikyan D, Tian W, Sadzikava N, Ross TM, Head E, Cribbs DH, et al. Generation and characterization of the humoral immune response to DNA immunization with a chimeric beta-amyloid-interleukin-4 minigene. Eur J Immunol 2003; 33:3232-41; PMID:14635031; http://dx.doi.org/10.1002/eji.200324000
46. Qu B, Rosenberg RN, Li L, Boyer PJ, Johnston SA. Gene vaccination to bias the immune response to amyloid-beta peptide as therapy for Alzheimer disease. Arch Neurol 2004; 61:1859-64; PMID:15596606; http://dx.doi.org/10.1001/archneur. 61.12.1859
47. Matsumoto Y, Niimi N, Kohyama K. Development of a new DNA vaccine for Alzheimer disease targeting a wide range of aβ species and amyloidogenic peptides. PLoS One 2013; 8:e75203; PMID:24086465; http://dx.doi.org/10.1371/ journal.pone.0075203
48. Lambracht-Washington D, Qu BX, Fu M, Anderson LD Jr., Eagar TN, Stüve O, Rosenberg RN. A peptide prime-DNA boost immunization protocol provides significant benefits as a new generation Aβ42 DNA vaccine for Alzheimer disease. J Neuroimmunol 2013; 254:63-8; PMID:23036592; http://dx.doi.org/10.1016/j.jneuroim.2012.09.008
49. Qu BX, Xiang Q, Li L, Johnston SA, Hynan LS, Rosenberg RN. Abeta42 gene vaccine prevents Abeta42 deposition in brain of double transgenic mice. J Neurol Sci 2007; 260:204-13; PMID:17574274; http://dx.doi.org/10.1016/j.jns.2007.05. 012
50. Subramanian S, Divya Shree AN. Enhanced Th2 immunity after DNA prime-protein boost immunization with amyloid beta (1-42) plus CpG oligodeoxynucleotides in aged rats. Neurosci Lett 2008; 436:219-22; PMID:18394801; http://dx.doi.org/10.1016/j.neulet.2008.03.024
51. Movsesyan N, Ghochikyan A, Mkrtichyan M, Petrushina I, Davtyan H, Olkhanud PB, Head E, Biragyn A, Cribbs DH, Agadjanyan MG. Reducing AD-like pathology in 3xTg-AD mouse model by DNA epitope vaccine - a novel immunotherapeutic strategy. PLoS One 2008; 3:e2124; PMID:18461171; http://dx.doi.org/10.1371/journal.pone.0002124
52. Davtyan H, Ghochikyan A, Movsesyan N, Ellefsen B, Petrushina I, Cribbs DH, Hannaman D, Evans CF, Agadjanyan MG. Delivery of a DNA vaccine for Alzheimer's disease by electroporation versus gene gun generates potent and similar immune responses. Neurodegener Dis 2012; 10:261-4; PMID:22301697; http://dx.doi.org/10.1159/000333359
53. Olkhanud PB, Mughal M, Ayukawa K, Malchinkhuu E, Bodogai M, Feldman N, Rothman S, Lee JH, Chigurupati S, Okun E, et al. DNA immunization with HBsAg-based particles expressing a B cell epitope of amyloid β-peptide attenuates disease progression and prolongs survival in a mouse model of Alzheimer's disease. Vaccine 2012; 30:1650-8; PMID:22248819; http://dx.doi.org/10.1016/j.vaccine.2011.12.136
54. Kim HD, Jin JJ, Maxwell JA, Fukuchi K. Enhancing Th2 immune responses against amyloid protein by a DNA prime-adenovirus boost regimen for Alzheimer's disease. Immunol Lett 2007; 112:30-8; PMID:17686533; http://dx.doi.org/10.1016/ j.imlet.2007.06.006
55. Yu YZ, Wang S, Bai JY, Zhao M, Chen A, Wang WB, Chang Q, Liu S, Qiu WY, Pang XB, et al. Effective DNA epitope chimeric vaccines for Alzheimer's disease using a toxin-derived carrier protein as a molecular adjuvant. Clin Immunol 2013; 149:11-24; PMID:23886550; http://dx.doi.org/10.1016/j.clim.2013.05.016
56. Ghochikyan A, Davtyan H, Petrushina I, Hovakimyan A, Movsesyan N, Davtyan A, Kiyatkin A, Cribbs DH, Agadjanyan MG. Refinement of a DNA based Alzheimer's disease epitope vaccine in rabbits. Hum Vaccin Immunother 2013; 9:1002-10; PMID:23399748; http://dx.doi.org/10.4161/hv.23875
57. Evans CF, Davtyan H, Petrushina I, Hovakimyan A, Davtyan A, Hannaman D, Cribbs DH, Agadjanyan MG, Ghochikyan A. Epitope-based DNA vaccine for Alzheimer's disease: Translational study in macaques. Alzheimers Dement 2013; (Forthcoming); PMID:23916838; http://dx.doi.org/10.1016/j.jalz.2013.04.505
58. Banga AK, Prausnitz MR. Assessing the potential of skin electroporation for the delivery of protein- and gene-based drugs. Trends Biotechnol 1998; 16:408-12; PMID:9807837; http://dx.doi.org/10.1016/S0167-7799(98)01238-4
59. Widera G, Austin M, Rabussay D, Goldbeck C, Barnett SW, Chen M, Leung L, Otten GR, Thudium K, Selby MJ, et al. Increased DNA vaccine delivery and immunogenicity by electroporation in vivo. J Immunol 2000; 164:4635-40; PMID:10779767
60. Rizzuto G, Cappelletti M, Maione D, Savino R, Lazzaro D, Costa P, Mathiesen I, Cortese R, Ciliberto G, Laufer R, et al. Efficient and regulated erythropoietin production by naked DNA injection and muscle electroporation. Proc Natl Acad Sci U S A 1999; 96:6417-22; PMID:10339602; http://dx.doi.org/10. 1073/pnas.96.11.6417
61. Gregoriadis G, Bacon A, Caparros-Wanderley W, McCormack B. A role for liposomes in genetic vaccination. Vaccine 2002; 20(Suppl 5):B1-9; PMID:12477411; http://dx.doi.org/10.1016/S0264-410X(02)00514-5
62. Laing P, Bacon A, McCormack B, Gregoriadis G, Frisch B, Schuber F. The 'co-delivery' approach to liposomal vaccines: application to the development of influenza-A and hepatitis-B vaccine candidates. J Liposome Res 2006; 16:229-35; PMID:16952877; http://dx.doi.org/10.1080/08982100600880432
63. Espuelas S, Thumann C, Heurtault B, Schuber F, Frisch B. Influence of ligand valency on the targeting of immature human dendritic cells by mannosylated liposomes. Bioconjug Chem 2008; 19:2385-93; PMID:19053315; http://dx.doi.org/10.1021/bc8002524