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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
Scientific reports, 01/2020, Volume: 10, Issue: 1Journal Article
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.
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