Adeno-associated virus (AAV) vector-based gene therapy offers a new treatment option for individuals with hemophilia. Pre-existing anti-AAV antibodies significantly impact the use of AAV vectors. Even relatively low titers of AAV neutralizing antibodies (NAb) from natural AAV infections against the capsid have been shown to inhibit the transduction of intravenously administered AAV in animal models and were associated with limited efficacy in human trials. This is important for determining the primary eligibility of patients for AAV vector-based gene therapy clinical trials. Current techniques to screen AAV antibodies include AAV capsid enzyme-linked immunosorbent assay (ELISA) for total antibodies and a transduction inhibition assay (TIA) for NAb. This study developed and screened total capsid binding anti-AAV3 antibodies by using ELISA and determined NAb levels by TIA using mCherry flow cytometry in healthy individuals with hemophilia B in India. One hundred and forty-three apparently healthy controls and 92 individuals with hemophilia B were screened. The prevalence of total and NAb in healthy controls was 79.7% and 65%, respectively; the prevalence of total and NAb in patients with hemophilia B for AAV3 was 92.4% and 91.3%, respectively.

中文翻译：

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印度健康和 B 型血友病患者中腺相关病毒 3 衣壳结合和中和抗体的流行情况

基于腺相关病毒 (AAV) 载体的基因治疗为血友病患者提供了一种新的治疗选择。预先存在的抗 AAV 抗体显着影响 AAV 载体的使用。在动物模型中，即使是来自天然 AAV 感染的相对低滴度的 AAV 中和抗体 (NAb) 也已显示抑制静脉内施用的 A​​AV 的转导，并且与人体试验中的有限功效相关。这对于确定基于 AAV 载体的基因治疗临床试验患者的主要资格非常重要。目前筛选 AAV 抗体的技术包括用于总抗体的 AAV 衣壳酶联免疫吸附试验 (ELISA) 和用于 NAb 的转导抑制试验 (TIA)。本研究使用 ELISA 开发和筛选总衣壳结合抗 AAV3 抗体，并通过 TIA 使用 mCherry 流式细胞术测定印度血友病 B 健康个体的 NAb 水平。筛选了 143 名明显健康的对照和 92 名 B 型血友病患者。健康对照组中总和 NAb 的患病率分别为 79.7% 和 65%；血友病 B 患者 AAV3 的总和 NAb 患病率分别为 92.4% 和 91.3%。