Effective Depletion of Pre-existing Anti-AAV Antibodies Requires Broad Immune Targeting

Molecular Therapy Methods and Clinical Development

Volumn 4, Issue , 2017, Pages 159-168

  Velazquez, Victoria M ^a   Meadows, Aaron S ^a   Pineda, Ricardo J ^a   Camboni, Marybeth ^a   McCarty, Douglas M ^a,b   Fu, Haiyan ^a  

^a THE RESEARCH INSTITUTE AT NATIONWIDE CHILDREN S HOSPITAL   (United States)

^b THE OHIO STATE UNIVERSITY COLLEGE OF MEDICINE   (United States)

Author keywords

AAV; gene therapy; pre existing antibody

Indexed keywords

BORTEZOMIB; FAS ANTIGEN; IMMUNOGLOBULIN D; IMMUNOGLOBULIN G; PREDNISOLONE; PROGRAMMED DEATH 1 RECEPTOR; PROTEIN; PROTEIN GL7; RAPAMYCIN; UNCLASSIFIED DRUG; VIRUS ANTIBODY;

ADENO ASSOCIATED VIRUS 9; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIBODY BLOOD LEVEL; ANTIBODY PRODUCTION; ARTICLE; B LYMPHOCYTE; B LYMPHOCYTE ACTIVATION; BONE MARROW; CD4+ T LYMPHOCYTE; CELL SURVIVAL; CONTROLLED STUDY; DOSE RESPONSE; DRUG EFFECT; DRUG EFFICACY; DRUG MEGADOSE; GENE THERAPY; GERMINAL CENTER; IMMUNE SYSTEM; IMMUNOMODULATION; LOW DRUG DOSE; MOUSE; NONHUMAN; PLASMA CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; SPLEEN; SPLEEN CELL; TH2 CELL;

EID: 85015649075     PISSN: None     EISSN: 23290501     Source Type: Journal    
DOI: 10.1016/j.omtm.2017.01.003     Document Type: Article

References (44)

1. 1 Nathwani, A.C., Tuddenham, E.G., Rangarajan, S., Rosales, C., McIntosh, J., Linch, D.C., Chowdary, P., Riddell, A., Pie, A.J., Harrington, C., et al. Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. N. Engl. J. Med. 365 (2011), 2357–2365.
2. 2 Manno, C.S., Pierce, G.F., Arruda, V.R., Glader, B., Ragni, M., Rasko, J.J., Ozelo, M.C., Hoots, K., Blatt, P., Konkle, B., et al. Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response. Nat. Med. 12 (2006), 342–347.
3. 3 Nathwani, A.C., Rosales, C., McIntosh, J., Rastegarlari, G., Nathwani, D., Raj, D., Nawathe, S., Waddington, S.N., Bronson, R., Jackson, S., et al. Long-term safety and efficacy following systemic administration of a self-complementary AAV vector encoding human FIX pseudotyped with serotype 5 and 8 capsid proteins. Mol. Ther. 19 (2011), 876–885.
4. 4 Foust, K.D., Wang, X., McGovern, V.L., Braun, L., Bevan, A.K., Haidet, A.M., Le, T.T., Morales, P.R., Rich, M.M., Burghes, A.H., Kaspar, B.K., Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN. Nat. Biotechnol. 28 (2010), 271–274.
5. 5 Fu, H., Dirosario, J., Killedar, S., Zaraspe, K., McCarty, D.M., Correction of neurological disease of mucopolysaccharidosis IIIB in adult mice by rAAV9 trans-blood-brain barrier gene delivery. Mol. Ther. 19 (2011), 1025–1033.
6. 6 Ruzo, A., Marcó, S., García, M., Villacampa, P., Ribera, A., Ayuso, E., Maggioni, L., Mingozzi, F., Haurigot, V., Bosch, F., Correction of pathological accumulation of glycosaminoglycans in central nervous system and peripheral tissues of MPSIIIA mice through systemic AAV9 gene transfer. Hum. Gene Ther. 23 (2012), 1237–1246.
7. 7 Foust, K.D., Nurre, E., Montgomery, C.L., Hernandez, A., Chan, C.M., Kaspar, B.K., Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes. Nat. Biotechnol. 27 (2009), 59–65.
8. 8 Duque, S., Joussemet, B., Riviere, C., Marais, T., Dubreil, L., Douar, A.M., Fyfe, J., Moullier, P., Colle, M.A., Barkats, M., Intravenous administration of self-complementary AAV9 enables transgene delivery to adult motor neurons. Mol. Ther. 17 (2009), 1187–1196.
9. 9 Boutin, S., Monteilhet, V., Veron, P., Leborgne, C., Benveniste, O., Montus, M.F., Masurier, C., 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. 21 (2010), 704–712.
10. 10 Calcedo, R., Vandenberghe, L.H., Gao, G., Lin, J., Wilson, J.M., Worldwide epidemiology of neutralizing antibodies to adeno-associated viruses. J. Infect. Dis. 199 (2009), 381–390.
11. 11 Scallan, C.D., Jiang, H., Liu, T., Patarroyo-White, S., Sommer, J.M., Zhou, S., Couto, L.B., Pierce, G.F., Human immunoglobulin inhibits liver transduction by AAV vectors at low AAV2 neutralizing titers in SCID mice. Blood 107 (2006), 1810–1817.
12. 12 Wang, L., Calcedo, R., Bell, P., Lin, J., Grant, R.L., Siegel, D.L., Wilson, J.M., Impact of pre-existing immunity on gene transfer to nonhuman primate liver with adeno-associated virus 8 vectors. Hum. Gene Ther. 22 (2011), 1389–1401.
13. 13 Louis Jeune, V., Joergensen, J.A., Hajjar, R.J., Weber, T., Pre-existing anti-adeno-associated virus antibodies as a challenge in AAV gene therapy. Hum. Gene Ther. Methods 24 (2013), 59–67.
14. 14 Wang, M., Crosby, A., Hastie, E., Samulski, J.J., McPhee, S., Joshua, G., Samulski, R.J., Li, C., Prediction of adeno-associated virus neutralizing antibody activity for clinical application. Gene Ther. 22 (2015), 984–992.
15. 15 Li, H., Lin, S.W., Giles-Davis, W., Li, Y., Zhou, D., Xiang, Z.Q., High, K.A., Ertl, H.C., A preclinical animal model to assess the effect of pre-existing immunity on AAV-mediated gene transfer. Mol. Ther. 17 (2009), 1215–1224.
16. 16 Meliani, A., Leborgne, C., Triffault, S., Jeanson-Leh, L., Veron, P., Mingozzi, F., Determination of anti-adeno-associated virus vector neutralizing antibody titer with an in vitro reporter system. Hum. Gene Ther. Methods 26 (2015), 45–53.
17. 17 Mingozzi, F., Anguela, X.M., Pavani, G., Chen, Y., Davidson, R.J., Hui, D.J., Yazicioglu, M., Elkouby, L., Hinderer, C.J., Faella, A., et al. Overcoming preexisting humoral immunity to AAV using capsid decoys. Sci. Transl. Med., 5, 2013, 194ra92.
18. 18 Maersch, S., Huber, A., Büning, H., Hallek, M., Perabo, L., Optimization of stealth adeno-associated virus vectors by randomization of immunogenic epitopes. Virology 397 (2010), 167–175.
19. 19 Asokan, A., Samulski, R.J., AAV does the shuffle. Nat. Biotechnol. 24 (2006), 158–160.
20. 20 Lee, G.K., Maheshri, N., Kaspar, B., Schaffer, D.V., PEG conjugation moderately protects adeno-associated viral vectors against antibody neutralization. Biotechnol. Bioeng. 92 (2005), 24–34.
21. 21 McIntosh, J.H., Cochrane, M., Cobbold, S., Waldmann, H., Nathwani, S.A., Davidoff, A.M., Nathwani, A.C., 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. 19 (2012), 78–85.
22. 22 Mingozzi, F., Chen, Y., Murphy, S.L., Edmonson, S.C., Tai, A., Price, S.D., Metzger, M.E., Zhou, S., Wright, J.F., Donahue, R.E., et al. Pharmacological modulation of humoral immunity in a nonhuman primate model of AAV gene transfer for hemophilia B. Mol. Ther. 20 (2012), 1410–1416.
23. 23 Corti, M., Elder, M., Falk, D., Lawson, L., Smith, B., Nayak, S., Conlon, T., Clément, N., Erger, K., Lavassani, E., et al. B-cell depletion is protective against anti-AAV capsid immune response: a human subject case study. Mol. Ther. Methods Clin. Dev., 1, 2014, 14033.
24. 24 Chicoine, L.G., Montgomery, C.L., Bremer, W.G., Shontz, K.M., Griffin, D.A., Heller, K.N., Lewis, S., Malik, V., Grose, W.E., Shilling, C.J., et al. Plasmapheresis eliminates the negative impact of AAV antibodies on microdystrophin gene expression following vascular delivery. Mol. Ther. 22 (2014), 338–347.
25. 25 Chicoine, L.G., Rodino-Klapac, L.R., Shao, G., Xu, R., Bremer, W.G., Camboni, M., Golden, B., Montgomery, C.L., Shontz, K., Heller, K.N., et al. Vascular delivery of rAAVrh74.MCK.GALGT2 to the gastrocnemius muscle of the rhesus macaque stimulates the expression of dystrophin and laminin α2 surrogates. Mol. Ther. 22 (2014), 713–724.
26. 26 Monteilhet, V., Saheb, S., Boutin, S., Leborgne, C., Veron, P., Montus, M.F., Moullier, P., Benveniste, O., Masurier, C., 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. 19 (2011), 2084–2091.
27. 27 Unzu, C., Hervás-Stubbs, S., Sampedro, A., Mauleón, I., Mancheño, U., Alfaro, C., de Salamanca, R.E., Benito, A., Beattie, S.G., Petry, H., et al. Transient and intensive pharmacological immunosuppression fails to improve AAV-based liver gene transfer in non-human primates. J. Transl. Med., 10, 2012, 122.
28. 28 Wine, Y., Horton, A.P., Ippolito, G.C., Georgiou, G., Serology in the 21st century: the molecular-level analysis of the serum antibody repertoire. Curr. Opin. Immunol. 35 (2015), 89–97.
29. 29 Kometani, K., Kurosaki, T., Differentiation and maintenance of long-lived plasma cells. Curr. Opin. Immunol. 33 (2015), 64–69.
30. 30 den Haan, J.M., Arens, R., van Zelm, M.C., The activation of the adaptive immune system: cross-talk between antigen-presenting cells, T cells and B cells. Immunol. Lett. 162:2 Pt B (2014), 103–112.
31. 31 Chu, V.T., Berek, C., The establishment of the plasma cell survival niche in the bone marrow. Immunol. Rev. 251 (2013), 177–188.
32. 32 Law, B.K., Rapamycin: an anti-cancer immunosuppressant?. Crit. Rev. Oncol. Hematol. 56 (2005), 47–60.
33. 33 Robak, T., Huang, H., Jin, J., Zhu, J., Liu, T., Samoilova, O., Pylypenko, H., Verhoef, G., Siritanaratkul, N., Osmanov, E., et al., LYM-3002 Investigators. Bortezomib-based therapy for newly diagnosed mantle-cell lymphoma. N. Engl. J. Med. 372 (2015), 944–953.
34. 34 DiRosario, J., Divers, E., Wang, C., Etter, J., Charrier, A., Jukkola, P., Auer, H., Best, V., Newsom, D.L., McCarty, D.M., Fu, H., Innate and adaptive immune activation in the brain of MPS IIIB mouse model. J. Neurosci. Res. 87 (2009), 978–990.
35. 35 Barnes, P.J., How corticosteroids control inflammation: Quintiles Prize Lecture 2005. Br. J. Pharmacol. 148 (2006), 245–254.
36. 36 Barnes, P.J., Glucocorticosteroids: current and future directions. Br. J. Pharmacol. 163 (2011), 29–43.
37. 37 Murrey, D.A., Naughton, B.J., Duncan, F.J., Meadows, A.S., Ware, T.A., Campbell, K.J., Bremer, W.G., Walker, C.M., Goodchild, L., Bolon, B., et al. Feasibility and safety of systemic rAAV9-hNAGLU delivery for treating mucopolysaccharidosis IIIB: toxicology, biodistribution, and immunological assessments in primates. Hum. Gene Ther. Clin. Dev. 25 (2014), 72–84.
38. 38 Inoue, S., Shibata, Y., Takabatake, N., Igarashi, A., Abe, S., Kubota, I., Influence of corticosteroid therapy on the serum antibody response to influenza vaccine in elderly patients with chronic pulmonary diseases. EXCLI J. 12 (2013), 760–765.
39. 39 Sberro-Soussan, R., Zuber, J., Suberbielle-Boissel, C., Candon, S., Martinez, F., Snanoudj, R., Rabant, M., Pallet, N., Nochy, D., Anglicheau, D., et al. Bortezomib as the sole post-renal transplantation desensitization agent does not decrease donor-specific anti-HLA antibodies. Am. J. Transplant. 10 (2010), 681–686.
40. 40 Zhang, Y., Hu, T., Hua, C., Gu, J., Zhang, L., Hao, S., Liang, H., Wang, X., Wang, W., Xu, J., et al. Rictor is required for early B cell development in bone marrow. PLoS ONE, 9, 2014, e103970.
41. 41 Iwata, T.N., Ramírez, J.A., Tsang, M., Park, H., Margineantu, D.H., Hockenbery, D.M., Iritani, B.M., Conditional disruption of Raptor reveals an essential role for mTORC1 in B cell development, survival, and metabolism. J. Immunol. 197 (2016), 2250–2260.
42. 42 Gerriets, V.A., Rathmell, J.C., Metabolic pathways in T cell fate and function. Trends Immunol. 33 (2012), 168–173.
43. 43 Schmitt, N., Ueno, H., Human T follicular helper cells: development and subsets. Adv. Exp. Med. Biol. 785 (2013), 87–94.
44. 44 Li, H.H., Yu, W.H., Rozengurt, N., Zhao, H.Z., Lyons, K.M., Anagnostaras, S., Fanselow, M.S., Suzuki, K., Vanier, M.T., Neufeld, E.F., Mouse model of Sanfilippo syndrome type B produced by targeted disruption of the gene encoding alpha-N-acetylglucosaminidase. Proc. Natl. Acad. Sci. USA 96 (1999), 14505–14510.