Author:
Bertin Berangere,Veron Philippe,Leborgne Christian,Deschamps Jack-Yves,Moullec Sophie,Fromes Yves,Collaud Fanny,Boutin Sylvie,Latournerie Virginie,van Wittenberghe Laetitia,Delache Benoit,Le Grand Roger,Dereuddre-Bosquet Nathalie,Benveniste Olivier,Moullier Philippe,Masurier Carole,Merten Otto,Mingozzi Federico
Abstract
AbstractNeutralizing 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.
Funder
Genethon
Agence Nationale de la Recherche
Publisher
Springer Science and Business Media LLC
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