Capsid-specific removal of circulating antibodies to adeno-associated virus vectors

Autor: Benoit Delache, Bérangère Bertin, Jack-Yves Deschamps, Virginie Latournerie, Carole Masurier, Christian Leborgne, Sophie Moullec, Olivier Benveniste, Roger Le Grand, Philippe Moullier, Fanny Collaud, Sylvie Boutin, Otto Wilhelm Merten, Philippe Veron, Laetitia van Wittenberghe, Yves Fromes, Nathalie Dereuddre-Bosquet, Federico Mingozzi
Přispěvatelé: Approches génétiques intégrées et nouvelles thérapies pour les maladies rares (INTEGRARE), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Généthon, Atlantic Gene Therapies [Nantes], Centre de Boisbonne [Nantes], Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was supported by Genethon. It was also supported by the European Union, ERC-2013-CoG Consolidator Grant, grant agreement number 617432 (MoMAAV, to F.M.), European Union’s research and innovation program under Grant Agreements No. 667751 (Myocure, to F.M.) and No. 755225 (CureCN, to F.M. and O.M.), E-Rare2 grant SMART-HaemoCare (to F.M.). This work was also supported by the 'Investissements d’Avenir' programs managed by the ANR under reference ANR-11-INBS-0008 funding the Infectious Disease Models and Innovative Therapies (IDMIT, Fontenay-aux-Roses, France), and ANR-10-EQPX-02–01 funding the FlowCyTech facility (IDMIT, Fontenay-aux-Roses, France)., ANR-11-INBS-0008,IDMIT,Infrastructure nationale pour la modélisation des maladies infectieuses humaines(2011), ANR-10-EQPX-0002,FlowCyTech,Plateforme de phénotypage en Mass cytométrie pour l'analyse multiparamétrique de biomarqueurs complexes de l'efficacité de nouvelles stratégies thérapeutiques ou vaccinales(2010), European Project: 617432,EC:FP7:ERC,ERC-2013-CoG,MOMAAV(2014), European Project: 667751,H2020,H2020-PHC-2015-two-stage,MYOCURE(2016), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Bodescot, Myriam, Infrastructures - Infrastructure nationale pour la modélisation des maladies infectieuses humaines - - IDMIT2011 - ANR-11-INBS-0008 - INBS - VALID, Equipements d'excellence - Plateforme de phénotypage en Mass cytométrie pour l'analyse multiparamétrique de biomarqueurs complexes de l'efficacité de nouvelles stratégies thérapeutiques ou vaccinales - - FlowCyTech2010 - ANR-10-EQPX-0002 - EQPX - VALID, Molecular signatures and Modulation of immunity to Adeno-Associated Virus vectors - MOMAAV - - EC:FP7:ERC2014-07-01 - 2019-06-30 - 617432 - VALID, Development of an innovative gene therapy platform to cure rare hereditary muscle disorders - MYOCURE - - H20202016-01-01 - 2019-12-31 - 667751 - VALID, Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche en Myologie
Jazyk: angličtina
Rok vydání: 2020
Předmět:
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology
0301 basic medicine
medicine.medical_treatment
viruses
Genetic Vectors
lcsh:Medicine
medicine.disease_cause
Antibodies
Viral
Virus
Article
03 medical and health sciences
Mice
0302 clinical medicine
Capsid
In vivo
Medicine
Animals
Humans
Vector (molecular biology)
lcsh:Science
Adeno-associated virus
[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology
Multidisciplinary
biology
Molecular medicine
business.industry
lcsh:R
Gene Transfer Techniques
[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology
Plasmapheresis
Translational research
Dependovirus
Virology
Antibodies
Neutralizing
3. Good health
Titer
030104 developmental biology
Preclinical research
030220 oncology & carcinogenesis
Immunoglobulin G
[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
biology.protein
lcsh:Q
Antibody
business
Zdroj: Scientific Reports
Scientific Reports, Nature Publishing Group, 2020, 10 (1), pp.864. ⟨10.1038/s41598-020-57893-z⟩
Scientific Reports, 2020, 10 (1), pp.864. ⟨10.1038/s41598-020-57893-z⟩
Scientific Reports, Vol 10, Iss 1, Pp 1-11 (2020)
ISSN: 2045-2322
Popis: Neutralizing antibodies directed against adeno-associated virus (AAV) are commonly found in humans. In seropositive subjects, vector administration is not feasible as antibodies neutralize AAV vectors even at low titers. Consequently, a relatively large proportion of humans is excluded from enrollment in clinical trials and, similarly, vector redosing is not feasible because of development of high-titer antibodies following AAV vector administration. Plasmapheresis has been proposed as strategy to remove anti-AAV antibodies from the bloodstream. Although safe and relatively effective, the technology has some limitations mainly related to the nonspecific removal of all circulating IgG. Here we developed an AAV-specific plasmapheresis column which was shown to efficiently and selectively deplete anti-AAV antibodies without depleting the total immunoglobulin pool from plasma. We showed the nearly complete removal of anti-AAV antibodies from high titer purified human IgG pools and plasma samples, decreasing titers to levels that allow AAV vector administration in mice. These results provide proof-of-concept of a method for the AAV-specific depletion of neutralizing antibodies in the setting of in vivo gene transfer.
Databáze: OpenAIRE
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