 |
Journal articles
Capsid-specific removal of circulating antibodies to adeno-associated virus vectors
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.
Cited literature [52 references]
https://www.hal.inserm.fr/inserm-02489693
Contributor : Myriam Bodescot <>
Submitted on : Monday, February 24, 2020 - 3:48:15 PM
Last modification on : Friday, March 5, 2021 - 3:00:29 AM
Contributor : Myriam Bodescot <>
Submitted on : Monday, February 24, 2020 - 3:48:15 PM
Last modification on : Friday, March 5, 2021 - 3:00:29 AM
File
s41598-020-57893-z.pdf
Publication funded by an institution
Licence
Distributed under a Creative Commons Attribution 4.0 International License