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神经肌肉疾病患者中针对 39 种人腺病毒类型的结合抗体和中和抗体的血清流行率。

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

机构信息

Institute for Virology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany.

Heimer Institute for Muscle Research, Department of Neurology, University Hospital Bergmannsheil, Ruhr-University Bochum, 44789 Bochum, Germany.

出版信息

Viruses. 2022 Dec 27;15(1):79. doi: 10.3390/v15010079.

DOI:10.3390/v15010079
PMID:36680119
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9866721/
Abstract

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.

摘要

高滴度的病毒载体预存抗体降低了其功能，可能导致不良反应。为了避免未来基因治疗方法中出现这一问题，我们检测了神经肌肉疾病（NMD）患者中一大类人腺病毒类型的血清流行率，以寻找适用于 NMD 基因替代治疗的病毒载体候选物。我们在 133 名 NMD 患者和 76 名年龄在 17-92 岁的健康对照者的血清中检测了针对 39 种人腺病毒的结合抗体和中和抗体，并分析了年龄、性别和 NMD 对抗体水平的影响。队列中不同腺病毒的血清流行率差异很大。针对 HAdV-D27、-C1、-D24、-D70、-B14、-C6、-D13、-B34 和 -E4 的结合抗体水平最高，而针对 HAdV-F41、-A31、-B11、-D75、-D8、-D65、-D26、-D80 和 -D17 的反应性最低。针对 HAdV-B3、-C2、-E4、-C1、-G52、-C5 和 -F41 的中和抗体反应性最高，而针对 HAdV-D74、-B34、-D73、-B37、-D48、-D13、-D75、-D8、-B35 和 -B16 的中和抗体反应性最低。我们未发现性别影响，不同年龄组之间也只有微小差异。重要的是，健康对照组和 NMD 患者之间没有显著差异。我们的数据表明，与健康个体相比，NMD 患者对 HAdV 的结合抗体和中和抗体水平非常相似，并且我们确定 HAdV-A31、-B16、-B34、-B35、-D8、-D37、-D48、-D73、-D74、-D75 和 -D80 是具有低结合和中和抗体流行率的有前途的载体开发候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09b/9866721/3e198e26d5de/viruses-15-00079-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09b/9866721/c83272366a12/viruses-15-00079-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09b/9866721/7dbc3385e1bc/viruses-15-00079-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09b/9866721/fffd1a4d2eb9/viruses-15-00079-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09b/9866721/53501c249a84/viruses-15-00079-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09b/9866721/568c79a13c3d/viruses-15-00079-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09b/9866721/8f6844d83dd3/viruses-15-00079-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09b/9866721/185b7a5b1d63/viruses-15-00079-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09b/9866721/e4173028abaa/viruses-15-00079-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09b/9866721/3e198e26d5de/viruses-15-00079-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09b/9866721/c83272366a12/viruses-15-00079-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09b/9866721/7dbc3385e1bc/viruses-15-00079-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09b/9866721/fffd1a4d2eb9/viruses-15-00079-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09b/9866721/53501c249a84/viruses-15-00079-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09b/9866721/568c79a13c3d/viruses-15-00079-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09b/9866721/8f6844d83dd3/viruses-15-00079-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09b/9866721/185b7a5b1d63/viruses-15-00079-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09b/9866721/e4173028abaa/viruses-15-00079-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09b/9866721/3e198e26d5de/viruses-15-00079-g009.jpg

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本文引用的文献

[1]
Analysis of the Prevalence of Binding and Neutralizing Antibodies against 39 Human Adenovirus Types in Student Cohorts Reveals Low-Prevalence Types and a Decline in Binding Antibody Levels during the SARS-CoV-2 Pandemic.

J Virol. 2022-11-23

[2]
Phase I, multicenter, open-label study of intravenous VCN-01 oncolytic adenovirus with or without nab-paclitaxel plus gemcitabine in patients with advanced solid tumors.

J Immunother Cancer. 2022-3

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Front Pediatr. 2020-11-23

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