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Journal articles
Capsid-specific removal of circulating antibodies to adeno-associated virus vectors
Berangere Bertin
1
Philippe Veron
1
Christian Leborgne
1
Jack-Yves Deschamps
2
Sophie Moullec
2
Yves Fromes
3
Fanny Collaud
1
Sylvie Boutin
1
Virginie Latournerie
1
Laetitia van Wittenberghe
1
Benoit Delache
4
Roger Le Grand
4
Nathalie Dereuddre-Bosquet
4
Olivier Benveniste
3, 5
Philippe Moullier
2
Carole Masurier
1
Otto Merten
1
Federico Mingozzi
1, *
Berangere Bertin 1
Mail :
Author IdHAL : berangere-bertin
Philippe Veron 1
Author
Christian Leborgne 1
Author
Jack-Yves Deschamps 2
Mail :
Author
Virginie Latournerie 1
Author
Laetitia van Wittenberghe 1
Author
Benoit Delache 4
Author
Roger Le Grand 4
Author
Nathalie Dereuddre-Bosquet 4
Author
Olivier Benveniste 3, 5
Mail :
Author
Philippe Moullier 2
Author
Carole Masurier 1
Author
Otto Merten 1
Author
Federico Mingozzi 1
Mail :
Correspondent author
1
Immunologie moléculaire et biothérapies innovantes (1bis, rue de l'Internationale - BP 60 - 91002 Evry Cedex - France)
- EPHE - École pratique des hautes études (4-14 Rue Ferrus, 75014 Paris - France)
- UEVE - Université d'Évry-Val-d'Essonne (Boulevard François Mitterrand 91025 Evry Cedex - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U951 (101, rue de Tolbiac, 75013 Paris - France)
- Genethon (France)
2
Atlantic Gene Therapies [Nantes] (France)
3
Centre de recherche en myologie (Bâtiment Babinski 47/83 Bd de L'Hôpital 75013 Paris - France)
- AFM-Téléthon - Association française contre les myopathies (1 rue de l'Internationale BP 59 91002 Evry cedex - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U974 (101, rue de Tolbiac, 75013 Paris - France)
- SU - Sorbonne Université (21 rue de l’École de médecine - 75006 Paris - France)
- CNRS - Centre National de la Recherche Scientifique : FRE3617 (France)
4
IMVA - U1184 - Immunologie des Maladies Virales et Autoimmunes (Site de l'Hôpital de Bicêtre - Faculté de Médecine Paris Sud - 63 rue Gabriel Péri 94276 Le Kremlin-Bicêtre Cedex.
Site du CEA de Fontenay-aux-Roses - 10, route du Panorama - BP 6 - 92265 Fontenay-aux-Roses. - France)
- UP11 - Université Paris-Sud - Paris 11 (Bâtiment 300 - 91405 Orsay cedex - France)
- CEA - Commissariat à l'énergie atomique et aux énergies alternatives : DRF/IMETI (Centre de Saclay Centre de Grenoble Centre de Cadarache etc - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1184 (101, rue de Tolbiac, 75013 Paris - France)
Abstract : 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.
Complete list of metadatas
https://www.hal.inserm.fr/inserm-02489693
Contributor : Myriam Bodescot <>
Submitted on : Monday, February 24, 2020 - 3:48:15 PM
Last modification on : Friday, April 17, 2020 - 11:04:19 AM
Contributor : Myriam Bodescot <>
Submitted on : Monday, February 24, 2020 - 3:48:15 PM
Last modification on : Friday, April 17, 2020 - 11:04:19 AM
File
s41598-020-57893-z.pdf
Publication funded by an institution
Licence
Distributed under a Creative Commons Attribution 4.0 International License
Identifiers
- HAL Id : inserm-02489693, version 1
- DOI : 10.1038/s41598-020-57893-z
- PUBMED : 31965041
- PUBMEDCENTRAL : PMC6972890
Collections
UNAM | CEA | U974 | SORBONNE-UNIVERSITE | UNIV-EVRY | SU-MEDECINE | EPHE | PSL | UNIV-PARIS-SACLAY | CNRS | INTEGRARE
Citation
Berangere Bertin, Philippe Veron, Christian Leborgne, Jack-Yves Deschamps, Sophie Moullec, et al.. Capsid-specific removal of circulating antibodies to adeno-associated virus vectors. Scientific Reports, Nature Publishing Group, 2020, 10 (1), pp.864. ⟨10.1038/s41598-020-57893-z⟩. ⟨inserm-02489693⟩
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