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Seroprevalence of Binding and Neutralizing Antibodies against 39 Human Adenovirus Types in Patients with Neuromuscular Disorders

High pre-existing antibodies against viral vectors reduce their functionality and may lead to adverse complications. To circumvent this problem in future gene therapy approaches, we tested the seroprevalence of a large range of human adenovirus types in patients with neuromuscular disorders (NMDs) t...

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Autores principales: Klann, Patrick Julian, Wang, Xiaoyan, Elfert, Anna, Zhang, Wenli, Köhler, Cornelia, Güttsches, Anne-Katrin, Jacobsen, Frank, Weyen, Ute, Roos, Andreas, Ehrke-Schulz, Eric, Ehrhardt, Anja, Vorgerd, Matthias, Bayer, Wibke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9866721/
https://www.ncbi.nlm.nih.gov/pubmed/36680119
http://dx.doi.org/10.3390/v15010079
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author Klann, Patrick Julian
Wang, Xiaoyan
Elfert, Anna
Zhang, Wenli
Köhler, Cornelia
Güttsches, Anne-Katrin
Jacobsen, Frank
Weyen, Ute
Roos, Andreas
Ehrke-Schulz, Eric
Ehrhardt, Anja
Vorgerd, Matthias
Bayer, Wibke
author_facet Klann, Patrick Julian
Wang, Xiaoyan
Elfert, Anna
Zhang, Wenli
Köhler, Cornelia
Güttsches, Anne-Katrin
Jacobsen, Frank
Weyen, Ute
Roos, Andreas
Ehrke-Schulz, Eric
Ehrhardt, Anja
Vorgerd, Matthias
Bayer, Wibke
author_sort Klann, Patrick Julian
collection PubMed
description High pre-existing antibodies against viral vectors reduce their functionality and may lead to adverse complications. To circumvent this problem in future gene therapy approaches, we tested the seroprevalence of a large range of human adenovirus types in patients with neuromuscular disorders (NMDs) to find appropriate viral vector candidates for gene replacement therapy for NMDs. Binding and neutralizing antibodies against 39 human adenovirus types were tested in the sera of 133 patients with NMDs and 76 healthy controls aged 17–92 years. The influence of age, sex, and NMDs on antibody levels was analyzed. The seroprevalence of different adenoviruses in the cohort varied widely. The highest levels of binding antibodies were detected against HAdV-D27, -C1, -D24, -D70, -B14, -C6, -D13, -B34, and -E4, whereas the lowest reactivity was detected against HAdV-F41, -A31, -B11, -D75, -D8, -D65, -D26, -D80, and -D17. The highest neutralizing reactivity was observed against HAdV-B3, -C2, -E4, -C1, -G52, -C5, and -F41, whereas the lowest neutralizing reactivity was observed against HAdV-D74, -B34, -D73, -B37, -D48, -D13, -D75, -D8, -B35, and -B16. We detected no influence of sex and only minor differences between different age groups. Importantly, there were no significant differences between healthy controls and patients with NMDs. Our data show that patients with NMDs have very similar levels of binding and neutralizing antibodies against HAdV compared to healthy individuals, and we identified HAdV-A31, -B16, -B34, -B35, -D8, -D37, -D48, -D73, -D74, -D75, and -D80 as promising candidates for future vector development due to their low binding and neutralizing antibody prevalence.
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spelling pubmed-98667212023-01-22 Seroprevalence of Binding and Neutralizing Antibodies against 39 Human Adenovirus Types in Patients with Neuromuscular Disorders Klann, Patrick Julian Wang, Xiaoyan Elfert, Anna Zhang, Wenli Köhler, Cornelia Güttsches, Anne-Katrin Jacobsen, Frank Weyen, Ute Roos, Andreas Ehrke-Schulz, Eric Ehrhardt, Anja Vorgerd, Matthias Bayer, Wibke Viruses Article High pre-existing antibodies against viral vectors reduce their functionality and may lead to adverse complications. To circumvent this problem in future gene therapy approaches, we tested the seroprevalence of a large range of human adenovirus types in patients with neuromuscular disorders (NMDs) to find appropriate viral vector candidates for gene replacement therapy for NMDs. Binding and neutralizing antibodies against 39 human adenovirus types were tested in the sera of 133 patients with NMDs and 76 healthy controls aged 17–92 years. The influence of age, sex, and NMDs on antibody levels was analyzed. The seroprevalence of different adenoviruses in the cohort varied widely. The highest levels of binding antibodies were detected against HAdV-D27, -C1, -D24, -D70, -B14, -C6, -D13, -B34, and -E4, whereas the lowest reactivity was detected against HAdV-F41, -A31, -B11, -D75, -D8, -D65, -D26, -D80, and -D17. The highest neutralizing reactivity was observed against HAdV-B3, -C2, -E4, -C1, -G52, -C5, and -F41, whereas the lowest neutralizing reactivity was observed against HAdV-D74, -B34, -D73, -B37, -D48, -D13, -D75, -D8, -B35, and -B16. We detected no influence of sex and only minor differences between different age groups. Importantly, there were no significant differences between healthy controls and patients with NMDs. Our data show that patients with NMDs have very similar levels of binding and neutralizing antibodies against HAdV compared to healthy individuals, and we identified HAdV-A31, -B16, -B34, -B35, -D8, -D37, -D48, -D73, -D74, -D75, and -D80 as promising candidates for future vector development due to their low binding and neutralizing antibody prevalence. MDPI 2022-12-27 /pmc/articles/PMC9866721/ /pubmed/36680119 http://dx.doi.org/10.3390/v15010079 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Klann, Patrick Julian
Wang, Xiaoyan
Elfert, Anna
Zhang, Wenli
Köhler, Cornelia
Güttsches, Anne-Katrin
Jacobsen, Frank
Weyen, Ute
Roos, Andreas
Ehrke-Schulz, Eric
Ehrhardt, Anja
Vorgerd, Matthias
Bayer, Wibke
Seroprevalence of Binding and Neutralizing Antibodies against 39 Human Adenovirus Types in Patients with Neuromuscular Disorders
title Seroprevalence of Binding and Neutralizing Antibodies against 39 Human Adenovirus Types in Patients with Neuromuscular Disorders
title_full Seroprevalence of Binding and Neutralizing Antibodies against 39 Human Adenovirus Types in Patients with Neuromuscular Disorders
title_fullStr Seroprevalence of Binding and Neutralizing Antibodies against 39 Human Adenovirus Types in Patients with Neuromuscular Disorders
title_full_unstemmed Seroprevalence of Binding and Neutralizing Antibodies against 39 Human Adenovirus Types in Patients with Neuromuscular Disorders
title_short Seroprevalence of Binding and Neutralizing Antibodies against 39 Human Adenovirus Types in Patients with Neuromuscular Disorders
title_sort seroprevalence of binding and neutralizing antibodies against 39 human adenovirus types in patients with neuromuscular disorders
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9866721/
https://www.ncbi.nlm.nih.gov/pubmed/36680119
http://dx.doi.org/10.3390/v15010079
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