{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:07:56Z","timestamp":1790104076742,"version":"4.0.1"},"reference-count":53,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T00:00:00Z","timestamp":1654732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Ophthalmological Society (DOG)","award":["MI 1238\/4-1"],"award-info":[{"award-number":["MI 1238\/4-1"]}]},{"name":"BMBF and MWK Lower Saxony-funded Professorinnenprogramm Niedersachsen","award":["MI 1238\/4-1"],"award-info":[{"award-number":["MI 1238\/4-1"]}]},{"name":"DFG-funded cluster of excellence REBIRTH","award":["MI 1238\/4-1"],"award-info":[{"award-number":["MI 1238\/4-1"]}]},{"name":"DFG-funded Priority Program 2127","award":["MI 1238\/4-1"],"award-info":[{"award-number":["MI 1238\/4-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Objectives: AAV vectors are widely used in gene therapy, but the prevalence of neutralizing antibodies raised against AAV serotypes in the course of a natural infection, as well as innate and adaptive immune responses induced upon vector administration, is still considered an important limitation. In ocular gene therapy, vectors applied subretinally bear the risk of retinal detachment or vascular leakage. Therefore, new AAV vectors that are suitable for intravitreal administration for photoreceptor transduction were developed. Methods: Here, we compared human immune responses from donors with suspected previous AAV2 infections to the new vectors AAV2.GL and AAV2.NN\u2014two capsid peptide display variants with an enhanced tropism for photoreceptors\u2014with the parental serotype AAV2 (AAV2 WT). We investigated total and neutralizing antibodies, adaptive and innate cellular immunogenicity determined by immunofluorescence staining and flow cytometry, and cytokine secretion analyzed with multiplex beads. Results: While we did not observe obvious differences in overall antibody binding, variants\u2014particularly AAV2.GL\u2014were less sensitive to neutralizing antibodies than the AAV2 WT. The novel variants did not differ from AAV2 WT in cellular immune responses and cytokine production in vitro. Conclusion: Due to their enhanced retinal tropism, which allows for dose reduction, the new vector variants are likely to be less immunogenic for gene therapy than the parental AAV2 vector.<\/jats:p>","DOI":"10.3390\/cells11121881","type":"journal-article","created":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T10:49:14Z","timestamp":1654771754000},"page":"1881","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Immunogenicity of Novel AAV Capsids for Retinal Gene Therapy"],"prefix":"10.3390","volume":"11","author":[{"given":"Miranda","family":"Gehrke","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University Hospital, LMU Munich, Mathildenstr. 8, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Diedrichs-M\u00f6hring","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital, LMU Munich, Mathildenstr. 8, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Bogedein","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital, LMU Munich, Mathildenstr. 8, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hildegard","family":"B\u00fcning","sequence":"additional","affiliation":[{"name":"Institute of Experimental Hematology, Hannover Medical School, Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5092-9238","authenticated-orcid":false,"given":"Stylianos","family":"Michalakis","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital, LMU Munich, Mathildenstr. 8, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhild","family":"Wildner","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital, LMU Munich, Mathildenstr. 8, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/s41573-019-0012-9","article-title":"Adeno-associated virus vector as a platform for gene therapy delivery","volume":"18","author":"Wang","year":"2019","journal-title":"Nat. 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