Pre-clinical assessment of immune responses to adeno-associated virus (AAV) vectors

Frontiers in Immunology

Volumn 5, Issue FEB, 2014, Pages

  Basner Tschakarjan, Etiena ^a   Bijjiga, Enoch ^b   Martino, Ashley T ^b  

^a CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

^b ST JOHN'S UNIVERSITY   (United States)

Author keywords

AAV; Adeno associated virus; Immune responses; Inhibitory AAV; Pre clinical models

Indexed keywords

BENZYLOXYCARBONYLLEUCYLLEUCYLLEUCINAL; BORTEZOMIB; CARFILZOMIB; CYCLOSPORIN A; GAMMA INTERFERON; INTERFERON; INTERLEUKIN 12; INTERLEUKIN 8; MACROGOL; NATURAL CYTOTOXICITY TRIGGERING RECEPTOR 1; PARVOVIRUS VECTOR; PATTERN RECOGNITION RECEPTOR; RITUXIMAB; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 9;

ANTIBODY TITER; CLINICAL TRIAL (TOPIC); CROSS REACTION; CYTOTOXIC T LYMPHOCYTE; CYTOTOXICITY; ENZYME LINKED IMMUNOSORBENT ASSAY; GENE EXPRESSION; HUMAN; HUMORAL IMMUNITY; IMMUNE RESPONSE; IMMUNOLOGICAL TOLERANCE; INNATE IMMUNITY; NONHUMAN; PERIPHERAL BLOOD MONONUCLEAR CELL; PLASMAPHERESIS; REGULATORY T LYMPHOCYTE; SEROPREVALENCE; SHORT SURVEY; SIGNAL TRANSDUCTION; VIRUS GENOME;

EID: 84895546715     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2014.00028     Document Type: Short Survey

References (57)

1. Erles K, Sebökovà P, Schlehofer JR. Update on the prevalence of serum antibodies (IgG and IgM) to adeno-associated virus (AAV). J Med Virol (1999) 59(3):406-11. doi:10.1002/(SICI)1096-9071(199911)59:3<::AID-JMV22>3.0.CO;2-N.
2. Blacklow NR, Hoggan MD, Rowe WP. Serologic evidence for human infection with adenovirus-associated viruses. J Natl Cancer Inst (1968) 40(2):319-27.
3. Boutin S, Monteilhet V, Veron P, Leborgne C, Benveniste O, Montus MF, et al. Prevalence of serum IgG and neutralizing factors against adeno-associated virus (AAV) types 1, 2, 5, 6, 8, and 9 in the healthy population: implications for gene therapy using AAV vectors. Hum Gene Ther (2010) 21(6):704-12. doi:10.1089/hum.2009.182.
4. Calcedo R, Vandenberghe LH, Gao G, Lin J, Wilson JM. Worldwide epidemiology of neutralizing antibodies to adeno-associated viruses. J Infect Dis (2009) 199(3):381-90. doi:10.1086/595830.
5. Niemeyer GP, Herzog RW, Mount J, Arruda VR, Tillson DM, Hathcock J, et al. Long-term correction of inhibitor-prone hemophilia B dogs treated with liver-directed AAV2-mediated factor IX gene therapy. Blood (2009) 113(4):797-806. doi:10.1182/blood-2008-10-181479.
6. Mingozzi F, Liu YL, Dobrzynski E, Kaufhold A, Liu JH, Wang Y, et al. Induction of immune tolerance to coagulation factor IX antigen by in vivo hepatic gene transfer. J Clin Invest (2003) 111(9):1347-56. doi:10.1172/JCI16887.
7. Dobrzynski E, Fitzgerald JC, Cao O, Mingozzi F, Wang L, Herzog RW. Prevention of cytotoxic T lymphocyte responses to factor IX-expressing hepatocytes by gene transfer-induced regulatory T cells. Proc Natl Acad Sci U S A (2006) 103(12):4592-7.
8. Manno CS, Pierce GF, Arruda VR, Glader B, Ragni M, Rasko JJ, et al. Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response. Nat Med (2006) 12(3):342-7. doi:10.1038/nm1358.
9. Nathwani AC, Tuddenham EG, Rangarajan S, Rosales C, McIntosh J, Linch DC, et al. Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. N Engl J Med (2011) 365(25):2357-65. doi:10.1056/NEJMoa1108046.
10. Brantly ML, Chulay JD, Wang L, Mueller C, Humphries M, Spencer LT, et al. Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1-AAT gene therapy. Proc Natl Acad Sci U S A (2009) 106(38):16363-8. doi:10.1073/pnas.0904514106.
11. Mingozzi F, Meulenberg JJ, Hui DJ, Basner-Tschakarjan E, Hasbrouck NC, Edmonson SA, et al. AAV-1-mediated gene transfer to skeletal muscle in humans results in dose-dependent activation of capsid-specific T cells. Blood (2009) 114(10):2077-86. doi:10.1182/blood-2008-07-167510.
12. Zaiss AK, Liu Q, Bowen GP, Wong NC, Bartlett JS, Muruve DA. Differential activation of innate immune responses by adenovirus and adeno-associated virus vectors. J Virol (2002) 76(9):4580-90. doi:10.1128/JVI.76.9.4580-4590.2002.
13. Zhu J, Huang X, Yang Y. The TLR9-MyD88 pathway is critical for adaptive immune responses to adeno-associated virus gene therapy vectors in mice. J Clin Invest (2009) 119(8):2388-98. doi:10.1172/JCI37607.
14. Martino AT, Suzuki M, Markusic DM, Zolotukhin I, Ryals RC, Moghimi B, et al. The genome of self-complementary adeno-associated viral vectors increases Toll-like receptor 9-dependent innate immune responses in the liver. Blood (2011) 117(24):6459-68. doi:10.1182/blood-2010-10-314518.
15. Hösel M, Broxtermann M, Janicki H, Esser K, Arzberger S, Hartmann P, et al. Toll-like receptor 2-mediated innate immune response in human nonparenchymal liver cells toward adeno-associated viral vectors. Hepatology (2012) 55(1):287-97. doi:10.1002/hep.24625.
16. Hensley SE, Amalfitano A. Toll-like receptors impact on safety and efficacy of gene transfer vectors. Mol Ther (2007) 15(8):1417-22. doi:10.1038/sj.mt.6300217.
17. Harbison CE, Weichert WS, Gurda BL, Chiorini JA, Agbandje-McKenna M, Parrish CR. Examining the cross-reactivity and neutralization mechanisms of a panel of mAbs against adeno-associated virus serotypes 1 and 5. J Gen Virol (2012) 93(Pt 2):347-55. doi:10.1099/vir.0.035113-0.
18. Scallan CD, Jiang H, Liu T, Patarroyo-White S, Sommer JM, Zhou S, et al. Human immunoglobulin inhibits liver transduction by AAV vectors at low AAV2 neutralizing titers in SCID mice. Blood (2006) 107(5):1810-7. doi:10.1182/blood-2005-08-3229.
19. Li C, Diprimio N, Bowles DE, Hirsch ML, Monahan PE, Asokan A, et al. Single amino acid modification of adeno-associated virus capsid changes transduction and humoral immune profiles. J Virol (2012) 86(15):7752-9. doi:10.1128/JVI.00675-12.
20. Li H, Lin SW, Giles-Davis W, Li Y, Zhou D, Xiang ZQ, et al. A preclinical animal model to assess the effect of pre-existing immunity on AAV-mediated gene transfer. Mol Ther (2009) 17(7):1215-24. doi:10.1038/mt.2009.79.
21. Ge Y, Powell S, Van Roey M, McArthur JG. Factors influencing the development of an anti-factor IX (FIX) immune response following administration of adeno-associated virus-FIX. Blood (2001) 97(12):3733-7. doi:10.1182/blood.V97.12.3733.
22. Maersch S, Huber A, Büning H, Hallek M, Perabo L. Optimization of stealth adeno-associated virus vectors by randomization of immunogenic epitopes. Virology (2010) 397(1):167-75. doi:10.1016/j.virol.2009.10.021.
23. Koerber JT, Maheshri N, Kaspar BK, Schaffer DV. Construction of diverse adeno-associated viral libraries for directed evolution of enhanced gene delivery vehicles. Nat Protoc (2006) 1(2):701-6. doi:10.1038/nprot.2006.93.
24. Asokan A, Samulski RJ. AAV does the shuffle. Nat Biotechnol (2006) 24(2):158-60. doi:10.1038/nbt0206-158.
25. Le HT, Yu QC, Wilson JM, Croyle MA. Utility of PEGylated recombinant adeno-associated viruses for gene transfer. J Control Release (2005) 108(1):161-77. doi:10.1016/j.jconrel.2005.07.019.
26. Lee GK, Maheshri N, Kaspar B, Schaffer DV. PEG conjugation moderately protects adeno-associated viral vectors against antibody neutralization. Biotechnol Bioeng (2005) 92(1):24-34. doi:10.1002/bit.20562.
27. Jang JH, Schaffer DV, Shea LD. Engineering biomaterial systems to enhance viral vector gene delivery. Mol Ther (2011) 19(8):1407-15. doi:10.1038/mt.2011.111.
28. McIntosh JH, Cochrane M, Cobbold S, Waldmann H, Nathwani SA, Davidoff AM, et al. Successful attenuation of humoral immunity to viral capsid and transgenic protein following AAV-mediated gene transfer with a non-depleting CD4 antibody and cyclosporine. Gene Ther (2012) 19(1):78-85. doi:10.1038/gt.2011.64.
29. Mingozzi F, Chen Y, Murphy SL, Edmonson SC, Tai A, Price SD, et al. Pharmacological modulation of humoral immunity in a nonhuman primate model of AAV gene transfer for hemophilia B. Mol Ther (2012) 20(7):1410-6. doi:10.1038/mt.2012.84.
30. Monteilhet V, Saheb S, Boutin S, Leborgne C, Veron P, Montus MF, et al. A 10 patient case report on the impact of plasmapheresis upon neutralizing factors against adeno-associated virus (AAV) types 1, 2, 6, and 8. Mol Ther (2011) 19(11):2084-91. doi:10.1038/mt.2011.108.
31. Mimuro J, Mizukami H, Hishikawa S, Ikemoto T, Ishiwata A, Sakata A, et al. Minimizing the inhibitory effect of neutralizing antibody for efficient gene expression in the liver with adeno-associated virus 8 vectors. Mol Ther (2013) 21(2):318-23. doi:10.1038/mt.2012.258.
32. Mingozzi F, Anguela XM, Pavani G, Chen Y, Davidson RJ, Hui DJ, et al. Overcoming preexisting humoral immunity to AAV using capsid decoys. Sci Transl Med (2013) 5:194ra92. doi:10.1126/scitranslmed.3005795.
33. Li H, Murphy HL, Giles-Davis W, Edmonson S, Xiang Z, Li Y, et al. Pre-existing AAV capsid-specific CD8+ T cells are unable to eliminate AAV-transduced hepatocytes. Mol Ther (2007) 15(4):792-800. doi:10.1038/mt.sj.6300090.
34. Wang L, Figueredo J, Calcedo R, Lin J, Wilson JM. Cross-presentation of adeno-associated virus serotype 2 capsids activates cytotoxic T cells but does not render hepatocytes effective cytolytic targets. Hum Gene Ther (2007) 18(3):185-94. doi:10.1089/hum.2007.001.
35. Jiang H, Couto LB, Patarroyo-White S, Liu T, Nagy D, Vargas JA, et al. Effects of transient immunosuppression on adenoassociated, virus-mediated, liver-directed gene transfer in rhesus macaques and implications for human gene therapy. Blood (2006) 108(10):3321-8. doi:10.1182/blood-2006-04-017913.
36. Gao G, Wang Q, Calcedo R, Mays L, Bell P, Wang L, et al. Adeno-associated virus-mediated gene transfer to nonhuman primate liver can elicit destructive transgene-specific T cell responses. Hum Gene Ther (2009) 20(9):930-42. doi:10.1089/hum.2009.060.
37. Nguyen DH, Hurtado-Ziola N, Gagneux P, Varki A. Loss of Siglec expression on T lymphocytes during human evolution. Proc Natl Acad Sci U S A (2006) 103(20):7765-70. doi:10.1073/pnas.0510484103.
38. Buchlis G, Odorizzi P, Soto PC, Pearce OMT, Hui DJ, Jordan MS, et al. Enhanced T cell function in a mouse model of human glycosylation. J Immunol (2013) 191(1):228-37. doi:10.4049/jimmunol.1202905.
39. Gil-Farina I, Di Scala M, Vanrell L, Olague C, Vales A, High KA, et al. IL12-mediated liver inflammation reduces the formation of AAV transcriptionally active forms but has no effect over preexisting AAV transgene expression. PLoS One (2013) 8(7):e67748. doi:10.1371/journal.pone.0067748.
40. Li H, Tuyishime S, Wu T, Giles-Davis W, Zhou D, Xiao W, et al. Adeno-associated virus vectors serotype 2 induce prolonged proliferation of capsid-specific CD8+ T cells in mice. Mol Ther (2011) 19(3):536-46. doi:10.1038/mt.2010.267.
41. Li C, Hirsch M, Asokan A, Zeithaml B, Ma H, Kafri T, et al. Adeno-associated virus type 2 (AAV2) capsid-specific cytotoxic T lymphocytes eliminate only vector-transduced cells coexpressing the AAV2 capsid in vivo. J Virol (2007) 81(14):7540-7. doi:10.1128/JVI.00529-07.
42. Finn JD, Hui DJ, Downey HD, Dunn D, Pien GC, Mingozzi F, et al. Proteasome inhibitors decrease AAV2 capsid-derived peptide epitope presentation on MHC class I following transduction. Mol Ther (2010) 18(1):135-42. doi:10.1038/mt.2009.257.
43. Pien GC, Basner-Tschakarjan E, Hui DJ, Mentlik AN, Finn JD, Hasbrouck NC, et al. Capsid antigen presentation flags human hepatocytes for destruction after transduction by adeno-associated viral vectors. J Clin Invest (2009) 119:1688-95. doi:10.1172/JCI36891.
44. Martino AT, Basner-Tschakarjan E, Markusic DM, Finn JD, Hinderer C, Zhou S, et al. Engineered AAV vector minimizes in vivo targeting of transduced hepatocytes by capsid-specific CD8 + T cells. Blood (2013) 121(12):2224-33. doi:10.1182/blood-2012-10-460733.
45. Aslanidi GV, Rivers AE, Ortiz L, Song L, Ling C, Govindasamy L, et al. Optimization of the capsid of recombinant adeno-associated virus 2 (AAV2) vectors: the final threshold? PLoS One (2013) 8(3):e59142. doi:10.1371/journal.pone.0059142.
46. Li C, Hirsch M, DiPrimio N, Asokan A, Goudy K, Tisch R, et al. Cytotoxic-T-lymphocyte-mediated elimination of target cells transduced with engineered adeno-associated virus type 2 vector in vivo. J Virol (2009) 83(13):6817-24. doi:10.1128/JVI.00278-09.
47. Johnson JS, Samulski RJ. Enhancement of adeno-associated virus infection by mobilizing capsids into and out of the nucleolus. J Virol (2009) 83(6):2632-44. doi:10.1128/JVI.02309-08.
48. Mitchell AM, Samulski RJ. Mechanistic insights into the enhancement of adeno-associated virus transduction by proteasome inhibitors. J Virol (2013) 87(23):13035-41. doi:10.1128/JVI.01826-13.
49. Ding W, Zhang L, Yan Z, Engelhardt JF. Intracellular trafficking of adeno-associated viral vectors. Gene Ther (2005) 12(11):873-80. Review. doi:10.1038/sj.gt.3302527.
50. Nathwani AC, Cochrane M, McIntosh J, Ng CY, Zhou J, Gray JT, et al. Enhancing transduction of the liver by adeno-associated viral vectors. Gene Ther (2009) 16(1):60-9. doi:10.1038/gt.2008.137.
51. Mitchell AM, Li C, Samulski RJ. Arsenic trioxide stabilizes accumulations of adeno-associated virus virions at the perinuclear region, increasing transduction in vitro and in vivo. J Virol (2013) 87(8):4571-83. doi:10.1128/JVI.03443-12.
52. Mingozzi F, Hasbrouck NC, Basner-Tschakarjan E, Edmonson SA, Hui DJ, Sabatino DE, et al. Modulation of tolerance to the transgene product in a nonhuman primate model of AAV-mediated gene transfer to liver. Blood (2007) 110(7):2334-41.
53. Moghimi B, Sack BK, Nayak S, Markusic DM, Mah CS, Herzog RW. Induction of tolerance to factor VIII by transient co-administration with rapamycin. J Thromb Haemost (2011) 9(8):1524-33. doi:10.1111/j.1538-7836.2011.04351.
54. Martino AT, Nayak S, Hoffman BE, Cooper M, Liao G, Markusic DM, et al. Tolerance induction to cytoplasmic beta-galactosidase by hepatic AAV gene transfer: implications for antigen presentation and immunotoxicity. PLoS One (2009) 4(8):e6376. doi:10.1371/journal.pone.0006376.
55. Zhang P, Sun B, Osada T, Rodriguiz R, Yang XY, Luo X, et al. Immunodominant liver-specific expression suppresses transgene-directed immune responses in murine pompe disease. Hum Gene Ther (2012) 23(5):460-72. doi:10.1089/hum.2011.063.
56. De Groot AS, Moise L, McMurry JA, Wambre E, Van Overtvelt L, Moingeon P, et al. Activation of natural regulatory T cells by IgG Fc-derived peptide "Tregitopes". Blood (2008) 112:3303-11. doi:10.1182/blood-2008-02-138073.
57. Hui DJ, Basner-Tschakarjan E, Chen Y, Davidson RJ, Buchlis G, Yazicioglu M, et al. Modulation of CD8+ T cell responses to AAV vectors with IgG-derived MHC class II epitopes. Mol Ther (2013) 21(9):1727-37. doi:10.1038/mt.2013.166.