Department of Molecular & Medical Genetics, Oregon Health & Science University School of Medicine, Portland, Oregon, 97239, USA.
Division of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon, 97006, United States of America.
Sci Rep. 2020 Jun 22;10(1):10073. doi: 10.1038/s41598-020-66596-4.
Cats are a critical pre-clinical model for studying adeno-associated virus (AAV) vector-mediated gene therapies. A recent study has described the high prevalence of anti-AAV neutralizing antibodies among domestic cats in Switzerland. However, our knowledge of pre-existing humoral immunity against various AAV serotypes in cats is still limited. Here, we show that, although antibodies binding known AAV serotypes (AAV1 to AAV11) are prevalent in cats living in the Northeastern United States, these antibodies do not necessarily neutralize AAV infectivity. We analyzed sera from 35 client-owned, 20 feral, and 30 specific pathogen-free (SPF) cats for pre-existing AAV-binding antibodies against the 11 serotypes. Antibody prevalence was 7 to 90% with an overall median of 50%. The AAV-binding antibodies showed broad reactivities with other serotypes. Of 44 selected antibodies binding AAV2, AAV6 or AAV9, none exhibited appreciable neutralizing activities. Instead, AAV6 or AAV9-binding antibodies showed a transduction-enhancing effect. AAV6-binding antibodies were highly prevalent in SPF cats (83%), but this was primarily due to cross-reactivity with preventive vaccine-induced anti-feline panleukopenia virus antibodies. These results indicate that prevalent pre-existing immunity in cats is not necessarily inhibitory to AAV and highlight a substantial difference in the nature of AAV-binding antibodies in cats living in geographically different regions.
猫是研究腺相关病毒（AAV）载体介导的基因治疗的重要临床前模型。最近的一项研究描述了瑞士家猫中抗 AAV 中和抗体的高流行率。然而，我们对猫体内各种 AAV 血清型的预先存在的体液免疫的了解仍然有限。在这里，我们表明，尽管生活在美国东北部的猫体内存在针对已知 AAV 血清型（AAV1 至 AAV11）的抗体，但这些抗体不一定能中和 AAV 的感染力。我们分析了 35 只家养猫、20 只野生猫和 30 只特定病原体自由（SPF）猫的血清，以检测针对 11 种血清型的预先存在的 AAV 结合抗体。抗体的流行率为 7%至 90%，总体中位数为 50%。AAV 结合抗体与其他血清型表现出广泛的反应性。在 44 种结合 AAV2、AAV6 或 AAV9 的抗体中，没有一种表现出明显的中和活性。相反，AAV6 或 AAV9 结合抗体表现出转导增强效应。AAV6 结合抗体在 SPF 猫中高度流行（83%），但这主要是由于与预防性疫苗诱导的抗猫泛白细胞减少症病毒抗体的交叉反应。这些结果表明，猫体内普遍存在的预先存在的免疫不一定对 AAV 具有抑制作用，并突出了生活在地理位置不同地区的猫体内 AAV 结合抗体的性质存在显著差异。
