Corden A, Handelman B, Yin H, Cotrim A, Alevizos I, Chiorini J A
Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Gene Ther. 2017 Apr;24(4):241-244. doi: 10.1038/gt.2017.1. Epub 2017 Feb 2.
One potential setback to the use of gene therapy for the treatment of Sjögren's syndrome is the presence of neutralizing antibodies (nAb) against adeno-associated virus (AAV) serotypes. In order to evaluate the efficacy of this treatment option, nAb titers were measured in both healthy individuals and Sjögren's patients. Several serotypes with known transduction activity in mouse salivary glands were tested and only AAV5 showed a statistically significant change in the prevalence of nAbs between Sjögren's and healthy participants. Both groups showed a higher rate of nAbs for AAV2 compared with most of the other serotypes tested, except for bovine AAV (BAAV). Although a similar rate of seropositivity was seen against BAAV and AAV2, the percentage of samples with high titer was significantly lower with BAAV. Furthermore, the majority of positive samples exhibited low nAb titers in the primary Sjögren's syndrome (pSS) group for all serotypes except for AAV2. AAV5 was the only serotype that showed a statistically significant shift in the percentage of medium or high neutralizing titer. Based on these results, many serotypes are viable vectors in a gene therapy approach and pSS patients do not have a statistically significant higher rate of seropositivity or titer compared with healthy donors.
使用基因疗法治疗干燥综合征的一个潜在挫折是存在针对腺相关病毒（AAV）血清型的中和抗体（nAb）。为了评估这种治疗选择的疗效，在健康个体和干燥综合征患者中均检测了nAb滴度。测试了几种在小鼠唾液腺中具有已知转导活性的血清型，只有AAV5在干燥综合征患者和健康参与者之间的nAb患病率上显示出统计学上的显著变化。与测试的大多数其他血清型相比，两组针对AAV2的nAb发生率更高，但牛腺相关病毒（BAAV）除外。尽管针对BAAV和AAV2的血清阳性率相似，但高滴度样本的百分比在BAAV中显著更低。此外，除AAV2外，在原发性干燥综合征（pSS）组中，所有血清型的大多数阳性样本均表现出低nAb滴度。AAV5是唯一在中和滴度为中等或高的百分比上显示出统计学显著变化的血清型。基于这些结果，在基因治疗方法中，许多血清型都是可行的载体，并且与健康供体相比，pSS患者的血清阳性率或滴度在统计学上没有显著更高。
