Strategies to circumvent humoral immunity to adeno-Associated viral vectors

Expert Opinion on Biological Therapy

Volumn 15, Issue 6, 2015, Pages 845-855

  Tse, Longping V ^a   Moller Tank, Sven ^a   Asokan, Aravind ^a  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

Adeno Associated virus; Capsid; Humoral immune response; Neutralizing antibody; Recombinant adeno Associated viral vectors

Indexed keywords

BIOLOGICAL PRODUCT; NEUTRALIZING ANTIBODY; PARVOVIRUS VECTOR;

APOPTOSIS; B LYMPHOCYTE ACTIVATION; CLINICAL TRIAL (TOPIC); DRUG TARGETING; GENETIC ENGINEERING; HOST; HUMAN; HUMORAL IMMUNITY; NONHUMAN; PLASMAPHERESIS; REVIEW; T LYMPHOCYTE ACTIVATION; VIRAL GENE THERAPY; VIRUS CAPSID; VIRUS ISOLATION; VIRUS RECOMBINANT; ADMINISTRATION AND DOSAGE; ANIMAL; AUTOIMMUNE DISEASES; DEPENDOPARVOVIRUS; GENE THERAPY; GENE VECTOR; GENETICS; IMMUNOLOGY; PROCEDURES; TRENDS;

ADENO-ASSOCIATED VIRUS; MIRIDAE;

ANIMALS; ANTIBODIES, NEUTRALIZING; AUTOIMMUNE DISEASES; DEPENDOVIRUS; GENETIC THERAPY; GENETIC VECTORS; HUMANS; IMMUNITY, HUMORAL;

EID: 84929884597     PISSN: 14712598     EISSN: 17447682     Source Type: Journal    
DOI: 10.1517/14712598.2015.1035645     Document Type: Review

References (112)

1. Atchison RW, Casto BC, Hammon WM. Adenovirus-Associated defective virus particles. Science 1965;149(3685):754-6
2. Mingozzi F, High KA. Therapeutic in vivo gene transfer for genetic disease using AAV: Progress and challenges. Nat Rev Genet 2011;12(5):341-55
3. Agbandje-McKenna M, Kleinschmidt J. AAV capsid structure and cell interactions. Methods Mol Biol 2011;807:47-92
4. Hamilton H, Gomos J, Berns KI, Falck-Pedersen E. Adeno-Associated virus site-specific integration and AAVS1 disruption. J Virol 2004;78(15):7874-82
5. Daya S, Cortez N, Berns KI. Adeno-Associated virus site-specific integration is mediated by proteins of the nonhomologous end-joining pathway. J Virol 2009;83(22):11655-64
6. Yalkinoglu AO, Heilbronn R, Burkle A, et al. DNA amplification of adenoassociated virus as a response to cellular genotoxic stress. Cancer Res 1988;48(11):3123-9
7. Daya S, Berns KI. Gene therapy using adeno-Associated virus vectors. Clin Microbiol Rev 2008;21(4):583-93
8. Sanlioglu S, Engelhardt JF. Cellular redox state alters recombinant adenoassociated virus transduction through tyrosine phosphatase pathways. Gene Ther 1999;6(8):1427-37
9. Vasileva A, Jessberger R. Precise hit: Adeno-Associated virus in gene targeting. Nat Rev Microbiol 2005;3(11):837-47
10. Clark KR, Sferra TJ, Johnson PR. Recombinant adeno-Associated viral vectors mediate long-Term transgene expression in muscle. Hum Gene Ther 1997;8(6):659-69
11. Nakai H, Storm TA, Kay MA. Recruitment of single-stranded recombinant adeno-Associated virus vector genomes and intermolecular recombination are responsible for stable transduction of liver in vivo. J Virol 2000;74(20):9451-63
12. Gao G, Alvira MR, Somanathan S, et al. Adeno-Associated viruses undergo substantial evolution in primates during natural infections. Proc Natl Acad Sci USA 2003;100(10):6081-6
13. Gao G, Vandenberghe LH, Alvira MR, et al. Clades of adeno-Associated viruses are widely disseminated in human tissues. J Virol 2004;78(12):6381-8
14. Asokan A, Schaffer DV, Samulski RJ. The AAV vector toolkit: Poised at the clinical crossroads. Mol Ther 2012;20(4):699-708
15. Kotterman MA, Schaffer DV. Engineering adeno-Associated viruses for clinical gene therapy. Nat Rev Genet 2014;15(7):445-51
16. Calcedo R, Vandenberghe LH, Gao G, et al. Worldwide epidemiology of neutralizing antibodies to adenoassociated viruses. J Infect Dis 2009;199(3):381-90
17. Harbison CE, Weichert WS, Gurda BL, et al. 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
18. Murphy SL, Li H, Zhou S, et al. Prolonged susceptibility to antibodymediated neutralization for adenoassociated vectors targeted to the liver. Mol Ther 2008;16(1):138-45
19. Scallan CD, Jiang H, Liu T, et al. Human immunoglobulin inhibits liver transduction by AAV vectors at low AAV2 neutralizing titers in SCID mice. Blood 2006;107(5):1810-17
20. Jiang H, Couto LB, Patarroyo-White S, et al. Effects of transient immunosuppression on adeno-Associated, virus-mediated, liver-directed gene transfer in rhesus macaques and implications for human gene therapy. Blood 2006;108(10):3321-8
21. Jaski BE, Jessup ML, Mancini DM, et al. Calcium upregulation by percutaneous administration of gene therapy in cardiac disease (CUPID trial), a first-in-human phase 1/2 clinical trial. J Card Fail 2009;15(3):171-81
22. Hajjar RJ, Zsebo K, Deckelbaum L, et al. Design of a phase 1/2 trial of intracoronary administration of AAV1/SERCA2a in patients with heart failure. J Card Fail 2008;14(5):355-67
23. Rapti K, Louis-Jeune V, Kohlbrenner E, et al. Neutralizing antibodies against AAV serotypes 1, 2, 6, and 9 in sera of commonly used animal models. Mol Ther 2012;20(1):73-83
24. Mimuro J, Mizukami H, Hishikawa S, et al. Minimizing the inhibitory effect of neutralizing antibody for efficient gene expression in the liver with adenoassociated virus 8 vectors. Mol Ther 2013;21(2):318-23
25. Calcedo R, Wilson JM. Humoral immune response to AAV Front Immunol 2013;4:341
26. Brantly ML, Chulay JD, Wang L, et al. Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1-AAT gene therapy. Proc Natl Acad Sci USA 2009;106(38):16363-8
27. Flotte TR, Trapnell BC, Humphries M, et al. Phase 2 clinical trial of a recombinant adeno-Associated viral vector expressing alpha1-Antitrypsin: Interim results. Hum Gene Ther 2011;22(10):1239-47
28. Manno CS, Chew AJ, Hutchison S, et al. AAV-mediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B. Blood 2003;101(8):2963-72
29. Treleaven CM, Tamsett TJ, Bu J, et al. Gene transfer to the CNS is efficacious in immune-primed mice harboring physiologically relevant titers of anti-AAV antibodies. Mol Ther 2012;20(9):1713-23
30. Hordeaux J, Dubreil L, Deniaud J, et al. Efficient central nervous system AAVrh10-mediated intrathecal gene transfer in adult and neonate rats. Gene Ther 2015. [Epub ahead of print]
31. Dayton RD, Wang DB, Klein RL. The advent of AAV9 expands applications for brain and spinal cord gene delivery. Expert Opin Biol Ther 2012;12(6):757-66
32. Haurigot V, Marco S, Ribera A, et al. Whole body correction of mucopolysaccharidosis IIIA by intracerebrospinal fluid gene therapy. J Clin Invest 2013;123(8):3254-71
33. Maguire AM, Simonelli F, Pierce EA, et al. Safety and efficacy of gene transfer for Lebers congenital amaurosis. N Engl J Med 2008;358(21):2240-8
34. Hauswirth WW, Aleman TS, Kaushal S, et al. Treatment of Leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adenoassociated virus gene vector: Short-Term results of a phase I trial. Hum Gene Ther 2008;19(10):979-90
35. Bainbridge JW, Smith AJ, Barker SS, et al. Effect of gene therapy on visual function in Lebers congenital amaurosis. N Engl J Med 2008;358(21):2231-9
36. Willett K, Bennett J. Immunology of AAV-mediated gene transfer in the eye. Front Immunol 2013;4:261
37. Herzog RW, Hagstrom JN, Kung SH, et al. Stable gene transfer and expression of human blood coagulation factor IX after intramuscular injection of recombinant adeno-Associated virus. Proc Natl Acad Sci USA 1997;94(11):5804-9
38. 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
39. Sun JY, Anand-Jawa V, Chatterjee S, Wong KK. Immune responses to adenoassociated virus and its recombinant vectors. Gene Ther 2003;10(11):964-76
40. Mingozzi F, Meulenberg JJ, Hui DJ, et al. AAV-1-mediated gene transfer to skeletal muscle in humans results in dose-dependent activation of capsidspecific T cells. Blood 2009;114(10):2077-86
41. Samaranch L, Salegio EA, San Sebastian W, et al. Adeno-Associated virus serotype 9 transduction in the central nervous system of nonhuman primates. Hum Gene Ther 2012;23(4):382-9
42. Samaranch L, Salegio EA, San Sebastian W, et al. Strong cortical and spinal cord transduction after AAV7 and AAV9 delivery into the cerebrospinal fluid of nonhuman primates. Hum Gene Ther 2013;24(5):526-32
43. Gray SJ, Matagne V, Bachaboina L, et al. Preclinical differences of intravascular AAV9 delivery to neurons and glia: A comparative study of adult mice and nonhuman primates. Mol Ther 2011;19(6):1058-69
44. Mays LE, Wang L, Tenney R, et al. Mapping the structural determinants responsible for enhanced T cell activation to the immunogenic adeno-Associated virus capsid from isolate rhesus 32.33. J Virol 2013;87(17):9473-85
45. Thwaite R, Pages G, Chillon M, Bosch A. AAVrh.10 immunogenicity in mice and humans. relevance of antibody cross-reactivity in human gene therapy. Gene Ther 2015;22(2):196-201
46. Carvalho LS, Zinn E, Shah S, et al. [120] retinal tropism of in silico reconstructed ancestral adeno-Associated viruses. Mol Ther 2014;22:S45
47. Tseng YS, Gurda BL, Chipman P, et al. Adeno-Associated virus serotype 1 (AAV1)- and AAV5-Antibody complex structures reveal evolutionary commonalities in parvovirus antigenic reactivity. J Virol 2015;89(3):1794-808
48. Lochrie MA, Tatsuno GP, Christie B, et al. Mutations on the external surfaces of adeno-Associated virus type 2 capsids that affect transduction and neutralization. J Virol 2006;80(2):821-34
49. Drouin LM, Agbandje-McKenna M. Adeno-Associated virus structural biology as a tool in vector development. Future Virol 2013;8(12):1183-99
50. Moskalenko M, Chen L, van Roey M, et al. Epitope mapping of human anti-Adeno-Associated virus type 2 neutralizing antibodies: Implications for gene therapy and virus structure. J Virol 2000;74(4):1761-6 . Early AAV antigenic epitope mapping studies.
51. Wobus CE, Hugle-Dorr B, Girod A, et al. Monoclonal antibodies against the adeno-Associated virus type 2 (AAV-2) capsid: Epitope mapping and identification of capsid domains involved in AAV-2-cell interaction and neutralization of AAV-2 infection. J Virol 2000;74(19):9281-93
52. Gurda BL, DiMattia MA, Miller EB, et al. Capsid antibodies to different adeno-Associated virus serotypes bind common regions. J Virol 2013;87(16):9111-24
53. McCraw DM, ODonnell JK, Taylor KA, et al. Structure of adenoassociated virus-2 in complex with neutralizing monoclonal antibody A20. Virology 2012;431(1-2):40-9
54. Romero PA, Arnold FH. Exploring protein fitness landscapes by directed evolution. Nat Rev Mol Cell Biol 2009;10(12):866-76
55. Bartel MA, Weinstein JR, Schaffer DV. Directed evolution of novel adenoassociated viruses for therapeutic gene delivery. Gene Ther 2012;19(6):694-700
56. Bartel M, Schaffer D, Buning H. Enhancing the clinical potential of AAV vectors by capsid engineering to evade pre-existing immunity. Front Microbiol 2011;2:204
57. Louis Jeune V, Joergensen JA, Hajjar RJ, Weber T. Pre-existing anti-Adeno-Associated virus antibodies as a challenge in AAV gene therapy. Hum Gene Ther Methods 2013;24(2):59-67
58. Haag R, Kratz F. Polymer therapeutics: Concepts and applications. Angew Chem Int Ed Engl 2006;45(8):1198-215
59. 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
60. Jang JH, Schaffer DV, Shea LD. Engineering biomaterial systems to enhance viral vector gene delivery. Mol Ther 2011;19(8):1407-15
61. Le HT, Yu QC, Wilson JM, Croyle MA. Utility of PEGylated recombinant adenoassociated viruses for gene transfer. J Control Release 2005;108(1):161-77
62. Espenlaub S, Wortmann A, Engler T, et al. Reductive amination as a strategy to reduce adenovirus vector promiscuity by chemical capsid modification with large polysaccharides. J Gene Med 2008;10(12):1303-14
63. Fisher KD, Stallwood Y, Green NK, et al. Polymer-coated adenovirus permits efficient retargeting and evades neutralising antibodies. Gene Ther 2001;8(5):341-8
64. Beer SJ, Matthews CB, Stein CS, et al. Poly (lactic-glycolic) acid copolymer encapsulation of recombinant adenovirus reduces immunogenicity in vivo. Gene Ther 1998;5(6):740-6
65. Sailaja G, HogenEsch H, North A, et al. Encapsulation of recombinant adenovirus into alginate microspheres circumvents vector-specific immune response. Gene Ther 2002;9(24):1722-9
66. Fitzpatrick Z, Gyorgy B, Skog J, Maguire CA. Extracellular vesicles as enhancers of virus vector-mediated gene delivery. Hum Gene Ther 2014;25(9):785-6
67. Garay RP, El-Gewely R, Armstrong JK, et al. Antibodies against polyethylene glycol in healthy subjects and in patients treated with PEG-conjugated agents. Expert Opin Drug Deliv 2012;9(11):1319-23
68. Mingozzi F, Anguela XM, Pavani G, et al. Overcoming preexisting humoral immunity to AAV using capsid decoys. Sci Transl Med 2013;5(194):194ra92
69. Gao K, Li M, Zhong L, et al. Empty virions in AAV8 vector preparations reduce transduction efficiency and may cause total viral particle dose-limiting side-effects. Mol Ther Methods Clin Dev 2014;1(9):20139
70. Pien GC, Basner-Tschakarjan E, Hui DJ, et al. Capsid antigen presentation flags human hepatocytes for destruction after transduction by adeno-Associated viral vectors. J Clin Invest 2009;119(6):1688-95
71. Levy HC, Bowman VD, Govindasamy L, et al. Heparin binding induces conformational changes in adenoassociated virus serotype 2. J Struct Biol 2009;165(3):146-56
72. Nony P, Chadeuf G, Tessier J, et al. Evidence for packaging of rep-cap sequences into adeno-Associated virus (AAV) type 2 capsids in the absence of inverted terminal repeats: A model for generation of rep-positive AAV particles. J Virol 2003;77(1):776-81
73. Huser D, Weger S, Heilbronn R. Packaging of human chromosome 19-specific adeno-Associated virus (AAV) integration sites in AAV virions during AAV wild-Type and recombinant AAV vector production. J Virol 2003;77(8):4881-7
74. Derksen RH, Schuurman HJ, Meyling FH, et al. The efficacy of plasma exchange in the removal of plasma components. J Lab Clin Med 1984;104(3):346-54
75. Buzzigoli SB, Genovesi M, Lambelet P, et al. Plasmapheresis treatment in Guillain-Barre syndrome: Potential benefit over intravenous immunoglobulin. Anaesth Intensive Care 2010;38(2):387-9
76. Erickson RW, Franklin WA, Emlen W. Treatment of hemorrhagic lupus pneumonitis with plasmapheresis. Semin Arthritis Rheum 1994;24(2):114-23
77. Chicoine LG, Montgomery CL, Bremer WG, et al. Plasmapheresis eliminates the negative impact of AAV antibodies on microdystrophin gene expression following vascular delivery. Mol Ther 2014;22(2):338-47
78. Monteilhet V, Saheb S, Boutin S, 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
79. Victora GD, Nussenzweig MC. Germinal centers. Annu Rev Immunol 2012;30:429-57
80. Carrasco YR, Batista FD. B cell recognition of membrane-bound antigen: An exquisite way of sensing ligands. Curr Opin Immunol 2006;18(3):286-91
81. Harwood NE, Batista FD. New insights into the early molecular events underlying B cell activation. Immunity 2008;28(5):609-19
82. Weber M, Treanor B, Depoil D, et al. Phospholipase C-gamma2 and Vav cooperate within signaling microclusters to propagate B cell spreading in response to membrane-bound antigen. J Exp Med 2008;205(4):853-68
83. Depoil D, Fleire S, Treanor BL, et al. CD19 is essential for B cell activation by promoting B cell receptor-Antigen microcluster formation in response to membrane-bound ligand. Nat Immunol 2008;9(1):63-72
84. Basner-Tschakarjan E, Bijjiga E, Martino AT. Pre-clinical assessment of immune responses to adeno-Associated virus (AAV) vectors. Front Immunol 2014;5:28
85. Karman J, Gumlaw NK, Zhang J, et al. Proteasome inhibition is partially effective in attenuating pre-existing immunity against recombinant adenoassociated viral vectors. PLoS One 2012;7(4):e34684
86. Neubert K, Meister S, Moser K, et al. The proteasome inhibitor bortezomib depletes plasma cells and protects mice with lupus-like disease from nephritis. Nat Med 2008;14(7):748-55
87. Gu H, Chen X, Gao G, Dong H. Caspase-2 functions upstream of mitochondria in endoplasmic reticulum stress-induced apoptosis by bortezomib in human myeloma cells. Mol Cancer Ther 2008;7(8):2298-307
88. Meister S, Schubert U, Neubert K, et al. Extensive immunoglobulin production sensitizes myeloma cells for proteasome inhibition. Cancer Res 2007;67(4):1783-92
89. Eeva J, Pelkonen J. Mechanisms of B cell receptor induced apoptosis. Apoptosis 2004;9(5):525-31
90. Bugatti S, Vitolo B, Caporali R, et al. B cells in rheumatoid arthritis: from pathogenic players to disease biomarkers. Biomed Res Int 2014;2014:681678
91. Smith MR. Rituximab (monoclonal anti- CD20 antibody): Mechanisms of action and resistance. Oncogene 2003;22(47):7359-68
92. Mingozzi F, Chen Y, Edmonson SC, et al. Prevalence and pharmacological modulation of humoral immunity to AAV vectors in gene transfer to synovial tissue. Gene Ther 2013;20(4):417-24
93. Mingozzi F, Chen Y, Murphy SL, et al. Pharmacological modulation of humoral immunity in a nonhuman primate model of AAV gene transfer for hemophilia B. Mol Ther 2012;20(7):1410-16
94. Corti M, Elder ME, Falk DJ, et al. B-cell depletion is protective against anti- AAV capsid immune response: A human subject case study. Mol Ther Methods Clin Dev 2014;14033
95. Ballou LM, Lin RZ. Rapamycin and mTOR kinase inhibitors. J Chem Biol 2008;1(1-4):27-36
96. Arin MJ, Engert A, Krieg T, Hunzelmann N. Anti-CD20 monoclonal antibody (rituximab) in the treatment of pemphigus. Br J Dermatol 2005;153(3):620-5
97. Chakraborty S, Tarantolo SR, Treves J, et al. Progressive multifocal leukoencephalopathy in a HIV-negative patient with small lymphocytic leukemia following treatment with rituximab. Case Rep Oncol 2011;4(1):136-42
98. Leandro MJ. B-cell subpopulations in humans and their differential susceptibility to depletion with anti- CD20 monoclonal antibodies. Arthritis Res Ther 2013;15(Suppl 1):S3
99. Sabatos-Peyton CA, Verhagen J, Wraith DC. Antigen-specific immunotherapy of autoimmune and allergic diseases. Curr Opin Immunol 2010;22(5):609-15
100. Miller A, Lider O, Roberts AB, et al. Suppressor T cells generated by oral tolerization to myelin basic protein suppress both in vitro and in vivo immune responses by the release of transforming growth factor beta after antigen-specific triggering. Proc Natl Acad Sci USA 1992;89(1):421-5
101. Skupsky J, Su Y, Lei TC, Scott DW. Tolerance induction by gene transfer to lymphocytes. Curr Gene Ther 2007;7(5):369-80
102. Muller J, Nitschke L. The role of CD22 and SIGLEC-G in B-cell tolerance and autoimmune disease. Nat Rev Rheumatol 2014;10(7):422-8
103. Pfrengle F, Macauley MS, Kawasaki N, Paulson JC. Copresentation of antigen and ligands of SIGLEC-G induces B cell tolerance independent of CD22. J Immunol 2013;191(4):1724-31
104. Doody GM, Justement LB, Delibrias CC, et al. A role in B cell activation for CD22 and the protein tyrosine phosphatase SHP. Science 1995;269(5221):242-4
105. Macauley MS, Pfrengle F, Rademacher C, et al. Antigenic liposomes displaying CD22 ligands induce antigen-specific B cell apoptosis. J Clin Invest 2013;123(7):3074-83
106. Xiao W, Chirmule N, Schnell MA, et al. Route of administration determines induction of T-cell-independent humoral responses to adeno-Associated virus vectors. Mol Ther 2000;1(4):323-9 . Importance of route of administration on AAV humoral immunity. 107.
107. Waldmann H, Adams E, Fairchild P, Cobbold S. Infectious tolerance and the long-Term acceptance of transplanted tissue. Immunol Rev 2006;212:301-13
108. Han SO, Li S, Brooks ED, et al. Enhanced efficacy from gene therapy in Pompe disease using coreceptor blockade. Hum Gene Ther 2015;26(1):26-35
109. De Groot AS, Moise L, McMurry JA, et al. Activation of natural regulatory T cells by IgG fc-derived peptide tregitopes. Blood 2008;112(8):3303-11
110. Hui DJ, Basner-Tschakarjan E, Chen Y, et al. Modulation of CD8+ T cell responses to AAV vectors with IgGderived MHC class II epitopes. Mol Ther 2013;21(9):1727-37
111. Halbert CL, Standaert TA, Wilson CB, Miller AD. Successful readministration of adeno-Associated virus vectors to the mouse lung requires transient immunosuppression during the initial exposure. J Virol 1998;72(12):9795-805
112. McIntosh JH, Cochrane M, Cobbold S, 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