Seroprevalence of anti-AAV antibodies in a healthy adult Spanish population: findings from the SAAVIA study

IF 5.9 3区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Gene Therapy Pub Date : 2026-03-12 DOI:10.1038/s41434-026-00597-2

Rafael Parra, Assumpció Bosch, Angela Sánchez, Cristina Caparros, Hae Kyung Kim, Nadia Lwoff

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Abstract

Adeno-associated virus (AAV) vectors are essential tools for gene therapy (GT), yet preexisting immunity can hinder their efficacy. This study examines the seroprevalence of total binding IgG against AAV serotypes 2, 5, 6, 8, and 9, and neutralizing antibodies (NAb) against AAV 6, 8, and 9 serotypes in a healthy adult Spanish population. Using enzyme-linked immunosorbent assays (ELISA) for IgG and luciferase-based assays for NAb, we found that IgG seroprevalence was highest for AAV6 (84.4%), followed by AAV2 (74.4%) and AAV8 (60.0%), with the lowest prevalence observed for AAV9 (51.2%) and AAV5 (40.4%). For NAb, AAV6 showed the highest prevalence (62.8%), followed by AAV8 (60.4%) and AAV9 (52.4%). Co-prevalence analysis revealed high rates among all IgG-AAV serotypes tested (ranging from 46.4% to 97.0%) and significant co-occurrence of NAb against AAV6, AAV8, and AAV9 (83.0% to 91.0%). High NAb levels correlated with high IgG levels in all samples. The variability in seroprevalence across populations highlights the importance of personalized and validated testing to optimize treatment outcomes and ensure the safety of AAV-based gene therapies.

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抗aav抗体在西班牙健康成人人群中的血清流行率：来自SAAVIA研究的结果

腺相关病毒（AAV）载体是基因治疗（GT）的重要工具，但先前存在的免疫可能会阻碍其疗效。本研究检测了西班牙健康成年人群中抗AAV 2、5、6、8和9血清型的总结合IgG的血清阳性率，以及抗AAV 6、8和9血清型的中和抗体（NAb）。采用酶联免疫吸附法（ELISA）检测IgG和荧光素酶法检测NAb，结果发现血清IgG阳性率最高的是AAV6(84.4%)，其次是AAV2（74.4%）和AAV8(60.0%)，最低的是AAV9（51.2%）和AAV5（40.4%）。NAb以AAV6患病率最高（62.8%），其次为AAV8（60.4%）和AAV9（52.4%）。共同患病率分析显示，所有IgG-AAV血清型的NAb发生率均较高（46.4%至97.0%），且NAb对AAV6、AAV8和AAV9的发生率显著共存（83.0%至91.0%）。在所有样本中，高NAb水平与高IgG水平相关。人群中血清阳性率的差异突出了个性化和验证测试的重要性，以优化治疗结果并确保基于aav的基因治疗的安全性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gene Therapy 医学-生化与分子生物学

CiteScore

9.70

自引率

2.00%

发文量

审稿时长

4-8 weeks

期刊介绍： Gene Therapy covers both the research and clinical applications of novel therapeutic techniques based on a genetic component. Over the last few decades, significant advances in technologies ranging from identifying novel genetic targets that cause disease through to clinical studies, which show therapeutic benefit, have elevated this multidisciplinary field to the forefront of modern medicine.