Perspective

Reduced Immunogenicity of Intraparenchymal Delivery of Adeno-Associated Virus Serotype 2 Vectors: Brief Overview

Author(s): Wuh-Liang Hwu, Shin-Ichi Muramatsu* and Bruria Gidoni-Ben-Zeev

Volume 22, Issue 3, 2022

Published on: 22 September, 2021

Page: [185 - 190] Pages: 6

DOI: 10.2174/1566523221666210922155413

open access plus

Abstract

Pre existing immunity to adeno-associated virus (AAV) poses a concern in AAV vector– mediated gene therapy. Localized administration of low doses of carefully chosen AAV serotypes can mitigate the risk of an immune response. This article will illustrate the low risk of immune response to AAV serotype 2 vector–mediated gene therapy to the brain with support from clinical trial data in aromatic L-amino acid decarboxylase deficiency and Parkinson disease.

Keywords: Adeno-associated virus, aromatic L-amino acid decarboxylase deficiency, eladocagene exuparvovec, immunogenicity, vectors, rare disease.

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Graphical Abstract
[1]
Haggerty DL, Grecco GG, Reeves KC, Atwood B. Adeno-associated viral vectors in neuroscience research. Mol Ther Methods Clin Dev 2019; 17: 69-82.
[http://dx.doi.org/10.1016/j.omtm.2019.11.012] [PMID: 31890742]
[2]
Ma CC, Wang ZL, Xu T, He ZY, Wei YQ. The approved gene therapy drugs worldwide: from 1998 to 2019. Biotechnol Adv 2020; 40: 107502.
[http://dx.doi.org/10.1016/j.biotechadv.2019.107502] [PMID: 31887345]
[3]
Mendell JR, Al-Zaidy SA, Rodino-Klapac LR, et al. Current clinical applications of in vivo gene therapy with AAVs. Mol Ther 2021; 29(2): 464-88.
[http://dx.doi.org/10.1016/j.ymthe.2020.12.007] [PMID: 33309881]
[4]
Wang D, Tai PWL, Gao G. Adeno-associated virus vector as a platform for gene therapy delivery. Nat Rev Drug Discov 2019; 18(5): 358-78.
[http://dx.doi.org/10.1038/s41573-019-0012-9] [PMID: 30710128]
[5]
Zhu D, Schieferecke AJ, Lopez PA, Schaffer DV. Adeno-associated virus vector for central nervous system gene therapy. Trends Mol Med 2021; 27(6): 524-37.
[http://dx.doi.org/10.1016/j.molmed.2021.03.010] [PMID: 33895085]
[6]
Calcedo R, Morizono H, Wang L, et al. Adeno-associated virus antibody profiles in newborns, children, and adolescents. Clin Vaccine Immunol 2011; 18(9): 1586-8.
[http://dx.doi.org/10.1128/CVI.05107-11] [PMID: 21775517]
[7]
Vandamme C, Adjali O, Mingozzi F. Unraveling the complex story of immune responses to AAV vectors trial after trial. Hum Gene Ther 2017; 28(11): 1061-74.
[http://dx.doi.org/10.1089/hum.2017.150] [PMID: 28835127]
[8]
ClinicalTrials.gov. RGX-111 Gene Therapy in Patients With MPS I (NCT03580083). 2020. Accessed May 13, 2021. https://clinicaltrials.gov/ct2/show/NCT03580083
[9]
ClinicalTrials.gov. RGX-121 Gene Therapy in Patients With MPS II (Hunter Syndrome) (NCT03566043). 2021. Accessed May 13, 2021. https://clinicaltrials.gov/ct2/show/NCT03566043
[10]
ClinicalTrials.gov. RGX-121 Gene Therapy in Children 5 Years of Age and Over With MPS II (Hunter Syndrome) (NCT04571970). 2021. Accessed May 13, 2021. https://clinicaltrials.gov/ct2/show/NCT04571970
[11]
ClinicalTrials.gov. Gene Therapy for Children With Variant Late Infantile Neuronal Ceroid Lipofuscinosis 6 (vLINCL6) Disease (NCT02725580). 2021. Accessed May 13, 2021. https://clinicaltrials.gov/ct2/show/NCT02725580
[12]
ClinicalTrials.gov. Gene Therapy for Children With CLN3 Batten Disease (NCT03770572). 2021. Accessed May 13, 2021. https://clinicaltrials.gov/ct2/show/NCT03770572
[13]
ClinicalTrials.gov. First-in-Human Study of TSHA-101 Gene Therapy for Treatment of Infantile Onset GM2 Gangliosidosis (NCT04798235). 2021. Accessed May 13, 2021. https://clinicaltrials.gov/ct2/show/NCT04798235
[14]
ClinicalTrials.gov. A Dose-escalation and Safety & Efficacy Study of AXO-AAV-GM2 in Tay-Sachs or Sandhoff Disease (NCT04669535). 2021. Accessed May 13, 2021. https://clinicaltrials.gov/ct2/show/NCT04669535
[15]
ClinicalTrials.gov. Intrathecal Administration of scAAV9/JeT-GAN for the Treatment of Giant Axonal Neuropathy (NCT02362438). 2021. Accessed May 13, 2021. https://clinicaltrials.gov/ct2/show/NCT02362438
[16]
Ciesielska A, Hadaczek P, Mittermeyer G, et al. Cerebral infusion of AAV9 vector-encoding non-self proteins can elicit cell-mediated immune responses. Mol Ther 2013; 21(1): 158-66.
[http://dx.doi.org/10.1038/mt.2012.167] [PMID: 22929660]
[17]
Fitzpatrick Z, Leborgne C, Barbon E, et al. Influence of pre-existing anti-capsid neutralizing and binding antibodies on AAV vector transduction. Mol Ther Methods Clin Dev 2018; 9: 119-29.
[http://dx.doi.org/10.1016/j.omtm.2018.02.003] [PMID: 29766022]
[18]
Gray SJ, Nagabhushan Kalburgi S, McCown TJ, Jude Samulski R. Global CNS gene delivery and evasion of anti-AAV-neutralizing antibodies by intrathecal AAV administration in non-human primates. Gene Ther 2013; 20(4): 450-9.
[http://dx.doi.org/10.1038/gt.2012.101] [PMID: 23303281]
[19]
Haurigot V, Marcó S, Ribera A, et al. Whole body correction of mucopolysaccharidosis IIIA by intracerebrospinal fluid gene therapy. J Clin Invest 2013; 123(8): 3254-71.
[http://dx.doi.org/10.1172/JCI66778] [PMID: 23863627]
[20]
Hocquemiller M, Giersch L, Audrain M, Parker S, Cartier N. Adeno-associated virus-based gene therapy for CNS diseases. Hum Gene Ther 2016; 27(7): 478-96.
[http://dx.doi.org/10.1089/hum.2016.087] [PMID: 27267688]
[21]
Hösel M, Broxtermann M, Janicki H, 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.
[http://dx.doi.org/10.1002/hep.24625] [PMID: 21898480]
[22]
Hudry E, Vandenberghe LH. Therapeutic AAV gene transfer to the nervous system: a clinical reality. Neuron 2019; 101(5): 839-62.
[http://dx.doi.org/10.1016/j.neuron.2019.02.017] [PMID: 30844402]
[23]
Ito M, Takino N, Nomura T, Kan A, Muramatsu SI. Engineered adeno-associated virus 3 vector with reduced reactivity to serum antibodies. Sci Rep 2021; 11(1): 9322.
[http://dx.doi.org/10.1038/s41598-021-88614-9] [PMID: 33927271]
[24]
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.
[http://dx.doi.org/10.1182/blood-2006-04-017913] [PMID: 16868252]
[25]
Lonser RR, Akhter AS, Zabek M, Elder JB, Bankiewicz KS. Direct convective delivery of adeno-associated virus gene therapy for treatment of neurological disorders. J Neurosurg 2020; 134: 1753-63.
[http://dx.doi.org/10.3171/2020.4.JNS20701] [PMID: 32915526]
[26]
Manno CS, Pierce GF, Arruda VR, 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.
[http://dx.doi.org/10.1038/nm1358] [PMID: 16474400]
[27]
Meyer K, Ferraiuolo L, Schmelzer L, et al. Improving single injection CSF delivery of AAV9-mediated gene therapy for SMA: a dose-response study in mice and nonhuman primates. Mol Ther 2015; 23(3): 477-87.
[http://dx.doi.org/10.1038/mt.2014.210] [PMID: 25358252]
[28]
Mingozzi F, High KA. Immune responses to AAV vectors: overcoming barriers to successful gene therapy. Blood 2013; 122(1): 23-36.
[http://dx.doi.org/10.1182/blood-2013-01-306647] [PMID: 23596044]
[29]
Nathwani AC, Tuddenham EG, Rangarajan S, et al. Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. N Engl J Med 2011; 365(25): 2357-65.
[http://dx.doi.org/10.1056/NEJMoa1108046] [PMID: 22149959]
[30]
Perez BA, Shutterly A, Chan YK, Byrne BJ, Corti M. Management of neuroinflammatory responses to aav-mediated gene therapies for neurodegenerative diseases. Brain Sci 2020; 10(2): E119.
[http://dx.doi.org/10.3390/brainsci10020119] [PMID: 32098339]
[31]
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.
[http://dx.doi.org/10.1089/hum.2013.005] [PMID: 23517473]
[32]
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.
[http://dx.doi.org/10.1089/hum.2011.200] [PMID: 22201473]
[33]
Samaranch L, Sebastian WS, Kells AP, et al. AAV9-mediated expression of a non-self protein in nonhuman primate central nervous system triggers widespread neuroinflammation driven by antigen-presenting cell transduction. Mol Ther 2014; 22(2): 329-37.
[http://dx.doi.org/10.1038/mt.2013.266] [PMID: 24419081]
[34]
Sánchez-Pernaute R, Harvey-White J, Cunningham J, Bankiewicz KS. Functional effect of adeno-associated virus mediated gene transfer of aromatic l-amino acid decarboxylase into the striatum of 6-OHDA-lesioned rats. Mol Ther 2001; 4(4): 324-30.
[http://dx.doi.org/10.1006/mthe.2001.0466] [PMID: 11592835]
[35]
Taghian T, Marosfoi MG, Puri AS, et al. A safe and reliable technique for CNS delivery of AAV vectors in the cisterna magna. Mol Ther 2020; 28(2): 411-21.
[http://dx.doi.org/10.1016/j.ymthe.2019.11.012] [PMID: 31813800]
[36]
Verdera HC, Kuranda K, Mingozzi F. AAV vector immunogenicity in humans: A long journey to successful gene transfer. Mol Ther 2020; 28(3): 723-46.
[http://dx.doi.org/10.1016/j.ymthe.2019.12.010] [PMID: 31972133]
[37]
Duan D. Systemic AAV micro-dystrophin gene therapy for Duchenne muscular dystrophy. Mol Ther 2018; 26(10): 2337-56.
[http://dx.doi.org/10.1016/j.ymthe.2018.07.011] [PMID: 30093306]
[38]
Martino AT, Suzuki M, Markusic DM, 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.
[http://dx.doi.org/10.1182/blood-2010-10-314518] [PMID: 21474674]
[39]
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.
[http://dx.doi.org/10.1128/JVI.76.9.4580-4590.2002] [PMID: 11932423]
[40]
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.
[http://dx.doi.org/10.1172/JCI37607] [PMID: 19587448]
[41]
Hinderer C, Nosratbakhsh B, Katz N, Wilson JM. A single injection of an optimized adeno-associated viral vector into cerebrospinal fluid corrects neurological disease in a murine model of GM1 gangliosidosis. Hum Gene Ther 2020; 31(21-22): 1169-77.
[http://dx.doi.org/10.1089/hum.2018.206] [PMID: 33045869]
[42]
Hordeaux J, Dubreil L, Robveille C, et al. Long-term neurologic and cardiac correction by intrathecal gene therapy in Pompe disease. Acta Neuropathol Commun 2017; 5(1): 66.
[http://dx.doi.org/10.1186/s40478-017-0464-2] [PMID: 28874182]
[43]
Bey K, Deniaud J, Dubreil L, et al. Intra-CSF AAV9 and AAVrh10 administration in nonhuman primates: Promising routes and vectors for which neurological diseases? Mol Ther Methods Clin Dev 2020; 17: 771-84.
[http://dx.doi.org/10.1016/j.omtm.2020.04.001] [PMID: 32355866]
[44]
Kaplitt MG, Feigin A, Tang C, et al. Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson’s disease: an open label, phase I trial. Lancet 2007; 369(9579): 2097-105.
[http://dx.doi.org/10.1016/S0140-6736(07)60982-9] [PMID: 17586305]
[45]
Chien YH, Lee NC, Tseng SH, et al. Efficacy and safety of AAV2 gene therapy in children with aromatic l-amino acid decarboxylase deficiency: an open-label, phase 1/2 trial. Lancet Child Adolesc Health 2017; 1(4): 265-73.
[http://dx.doi.org/10.1016/S2352-4642(17)30125-6] [PMID: 30169182]
[46]
Christine CW, Starr PA, Larson PS, et al. Safety and tolerability of putaminal AADC gene therapy for Parkinson disease. Neurology 2009; 73(20): 1662-9.
[http://dx.doi.org/10.1212/WNL.0b013e3181c29356] [PMID: 19828868]
[47]
Heiss JD, Lungu C, Hammoud DA, et al. Trial of magnetic resonance-guided putaminal gene therapy for advanced Parkinson’s disease. Mov Disord 2019; 34(7): 1073-8.
[http://dx.doi.org/10.1002/mds.27724] [PMID: 31145831]
[48]
Mittermeyer G, Christine CW, Rosenbluth KH, et al. Long-term evaluation of a phase 1 study of AADC gene therapy for Parkinson’s disease. Hum Gene Ther 2012; 23(4): 377-81.
[http://dx.doi.org/10.1089/hum.2011.220] [PMID: 22424171]
[49]
Muramatsu S, Fujimoto K, Kato S, et al. A phase I study of aromatic L-amino acid decarboxylase gene therapy for Parkinson’s disease. Mol Ther 2010; 18(9): 1731-5.
[http://dx.doi.org/10.1038/mt.2010.135] [PMID: 20606642]
[50]
Rosenberg JB, Kaplitt MG, De BP, et al. AAVrh.10-mediated APOE2 central nervous system gene therapy for APOE4-associated Alzheimer’s disease. Hum Gene Ther Clin Dev 2018; 29(1): 24-47.
[http://dx.doi.org/10.1089/humc.2017.231] [PMID: 29409358]
[51]
Leone P, Shera D, McPhee SW, et al. Long-term follow-up after gene therapy for canavan disease. Sci Transl Med 2012; 4(165): 165ra163.
[http://dx.doi.org/10.1126/scitranslmed.3003454] [PMID: 23253610]
[52]
Hwu WL, Muramatsu S, Tseng SH, et al. Gene therapy for aromatic l-amino acid decarboxylase deficiency. Sci Transl Med 2012; 4(134): 134ra61.
[http://dx.doi.org/10.1126/scitranslmed.3003640] [PMID: 22593174]
[53]
ClinicalTrials.gov. Study of AAVrh10-h.SGSH Gene Therapy in Patients With Mucopolysaccharidosis Type IIIA (MPS IIIA) (AAVance) (NCT03612869). 2020. Accessed May 17, 2021. https://clinicaltrials.gov/ct2/show/NCT03612869?term=aav&draw=12&rank=101
[54]
Himmelreich N, Montioli R, Bertoldi M, et al. Aromatic amino acid decarboxylase deficiency: Molecular and metabolic basis and therapeutic outlook. Mol Genet Metab 2019; 127(1): 12-22.
[http://dx.doi.org/10.1016/j.ymgme.2019.03.009] [PMID: 30952622]
[55]
Wassenberg T, Molero-Luis M, Jeltsch K, et al. Consensus guideline for the diagnosis and treatment of aromatic l-amino acid decarboxylase (AADC) deficiency. Orphanet J Rare Dis 2017; 12(1): 12.
[http://dx.doi.org/10.1186/s13023-016-0522-z] [PMID: 28100251]
[56]
Kuwabara H, Cumming P, Reith J, et al. Human striatal l-dopa decarboxylase activity estimated in vivo using 6-[18F]fluoro-dopa and positron emission tomography: error analysis and application to normal subjects. J Cereb Blood Flow Metab 1993; 13(1): 43-56.
[http://dx.doi.org/10.1038/jcbfm.1993.7] [PMID: 8417009]
[57]
Ito T, Yamamoto S, Hayashi T, et al. A convenient enzyme-linked immunosorbent assay for rapid screening of anti-adeno-associated virus neutralizing antibodies. Ann Clin Biochem 2009; 46(Pt 6): 508-10.
[http://dx.doi.org/10.1258/acb.2009.009077] [PMID: 19729501]
[58]
Kojima K, Nakajima T, Taga N, et al. Gene therapy improves motor and mental function of aromatic l-amino acid decarboxylase deficiency. Brain 2019; 142(2): 322-33.
[http://dx.doi.org/10.1093/brain/awy331] [PMID: 30689738]

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