{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:15:40Z","timestamp":1787026540578,"version":"build-2736575974"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T00:00:00Z","timestamp":1695340800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007560","name":"Chiesi Farmaceutici","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007560","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Polyethylene glycol (PEG)ylated drugs are used for medical treatment, since PEGylation either decreases drug clearance or\/and shields the protein from undesirable immunogenicity. PEGylation was implemented in a new enzyme replacement therapy for Fabry disease (FD), pegunigalsidase-alfa (PRX-102). However, exposure to PEG via life-style products and vaccination can result in the formation of anti-PEG antibodies. We demonstrate the\n                    <jats:italic>de novo<\/jats:italic>\n                    formation of functional anti-PEG antibodies in a healthy male after the second mRNA-based vaccination against SARS-CoV-2. Consequently, we analyzed the frequency and inhibitory function of anti-PEG and anti-\u03b1-Galactosidase A (AGAL) antibodies in 102 FD patients (46.9% males). We identified 29 out of 87 (33.3%) patients with low anti-PEG titers. Sera from patients without anti-AGAL antibodies [n=70] showed a higher rescued AGAL activity of agalsidase-beta and PRX-102 [both p&amp;lt;0.0001] compared to those with anti-AGAL antibodies [n=15]. Sera from anti-AGAL antibody-negative and -positive patients had less inhibitory effects on PRX-102 (rescued activity: 89 \u00b1 6% versus 85 \u00b1 7% and 49 \u00b1 26% versus 25 \u00b1 32%; both p&amp;lt;0.0001). Enzyme stability assays demonstrated that AUCs in anti-AGAL-negative sera (n=20) were 7.6-fold higher for PRX-102, while AUCs of both enzymes in anti-AGAL-positive sera (n=6) were decreased. However, AUC for PRX-102 was 33% of non-anti-AGAL-positive sera treated PRX-102 and 5-fold higher compared to agalsidase-beta. Anti-PEG antibodies had no significant effects on serum half-life of PRX-102, probably due to low titers. Conceivably, therapy efficacy may be superior under next-generation PRX-102 therapy compared to current enzyme replacement therapies in terms of reduced inhibitory effects of anti-AGAL and minor inhibitory effects of anti-PEG antibodies.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2023.1266082","type":"journal-article","created":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T05:22:42Z","timestamp":1695360162000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Characterization of pre-existing anti-PEG and anti-AGAL antibodies towards PRX-102 in patients with Fabry disease"],"prefix":"10.3389","volume":"14","author":[{"given":"Malte","family":"Lenders","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina Marleen","family":"Feidicker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan-Martin","family":"Brand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Brand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61589-5","article-title":"Fabry\u2019s disease","volume":"372","author":"Zarate","year":"2008","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1056\/NEJM200107053450102","article-title":"Safety and efficacy of recombinant human alpha-galactosidase A replacement therapy in Fabry\u2019s disease","volume":"345","author":"Eng","year":"2001","journal-title":"N Engl J 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Metab"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2014.08.002","article-title":"Characterization of a chemically modified plant cell culture expressed human a-Galactosidase-A enzyme for treatment of Fabry disease","volume":"114","author":"Kizhner","year":"2015","journal-title":"Mol Genet Metab"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1021\/acs.bioconjchem.8b00133","article-title":"Development and analytical characterization of pegunigalsidase alfa, a chemically cross-linked plant recombinant human a-galactosidase-A for treatment of Fabry disease","volume":"29","author":"Ruderfer","year":"2018","journal-title":"Bioconjug Chem"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12080","article-title":"Pegunigalsidase alfa, a novel PEGylated enzyme replacement therapy for Fabry disease, provides sustained plasma concentrations and favorable pharmacodynamics: a 1-year Phase 1\/2 clinical trial","volume":"42","author":"Schiffmann","year":"2019","journal-title":"J Inherit Metab Dis"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2022.07.009","article-title":"Pre-existing anti-drug antibodies in Fabry disease show less affinity for pegunigalsidase alfa","volume":"26","author":"Lenders","year":"2022","journal-title":"Mol Ther Methods Clin Dev"},{"key":"B14","doi-asserted-by":"publisher","first-page":"114079","DOI":"10.1016\/j.addr.2021.114079","article-title":"To PEGylate or not to PEGylate: Immunological properties of nanomedicine's most popular component, polyethylene glycol and its alternatives","volume":"180","author":"Shi","year":"2022","journal-title":"Adv Drug Delivery Rev"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1080\/14686996.2019.1627174","article-title":"PEGylated liposomes: immunological responses","volume":"20","author":"Mohamed","year":"2019","journal-title":"Sci Technol Adv 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randomized, phase 3 ATTRACT study","volume":"131","author":"Feldt-Rasmussen","year":"2020","journal-title":"Mol Genet Metab"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/ehjcvp\/pvab025","article-title":"Treatment of Fabry disease with migalastat-outcome from a prospective 24 months observational multicenter study (FAMOUS)","volume":"8","author":"Lenders","year":"2022","journal-title":"Eur Heart J Cardiovasc Pharmacother"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2022.10.007","article-title":"Antibodies against recombinant enzyme in the treatment of Fabry disease: Now you see them, now you don't","volume":"27","author":"Van der Veen","year":"2022","journal-title":"Mol Ther Methods Clin Dev"}],"container-title":["Frontiers in 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