Inflammatory Bowel Diseases

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Inflammatory Bowel Diseases:
doi: 10.1002/ibd.21673
Original Article

Neutralizing antibodies against adeno‐associated viruses in inflammatory bowel disease patients: Implications for gene therapy

van der Marel, Sander MD1,2,*; Comijn, Elisabeth M. BSc1; Verspaget, Hein W. PhD2; van Deventer, Sander MD, PhD1,2; van den Brink, Gijs R. MD, PhD3,4; Petry, Harald PhD1; Hommes, Daniel W. MD, PhD2; Ferreira, Valerie PhD1

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Background:: Inflammatory bowel diseases (IBDs) are comprised of two major disorders: Crohn's disease (CD) and ulcerative colitis (UC). No curative treatment options are available, but gene therapy may offer an alternative therapeutic approach. For this a safe and reliable vector is needed. The adeno‐associated viruses (AAV) have attracted considerable interest as gene therapy vectors. However, neutralizing antibodies (nAb's) made in response to wildtype AAV have been associated with a partial to complete block of transduction in case of reexposure. Therefore, and in order to define AAV vector candidates to treat IBD patients, we characterized preexisting humoral responses to AAV in this population.

Methods:: We measured circulating antibodies against AAV serotypes 1, 2, 3, 4, 5, 6, and 8 using a previously established virus neutralization assay. In all, 100 healthy donors and 200 IBD patient's serum samples (101 CD and 99 UC) were analyzed.

Results:: A significant difference was detected in the prevalence of nAb's for AAV types 1, 5, 6, and 8 between the healthy donors and the patient population. Furthermore, various disease phenotypic characteristics correlated with the prevalence of nAb's to all the serotypes studied.

Conclusions:: Our study establishes a foundation for the development of an AAV‐based gene therapy approach as a novel treatment for IBD. Furthermore, we show a relationship between disease phenotype in IBD patients and the humoral immune response to AAV.

© Crohn's & Colitis Foundation of America, Inc.

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