Prevalence of neutralizing antibodies against liver-tropic adeno-associated virus serotype vectors in 100 healthy Chinese and its potential relation to body constitutions
Prevalence of neutralizing antibodies against liver-tropic adeno-associated virus serotype vectors in 100 healthy Chinese and its potential relation to body constitutions
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DOI：
10.1016/s2095-4964(15)60200-x
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发表时间：
2015-09-01
影响因子：
4.8
通讯作者：
Ling, Chang-Quan
中科院分区：
文献类型：
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作者：
Ling, Chen;Wang, Yuan;Ling, Chang-Quan
重组腺相关病毒(RAAV)血清2型、3型和8型载体是目前最有前景的嗜肝AAV血清型载体。肝脏疾病是中国的重大问题。然而，到目前为止，关于AAV中和抗体(NAB)的研究很少与中国人或rAAV3载体合作。本研究旨在确定中国人群中针对AAV2、AAV3和AAV8野生型衣壳蛋白以及另外两个AAV3变异株的NAB的患病率。此外，我们还进行了初步分析，以探讨中医体质对AAV NAB的潜在影响。我们的工作表明，大多数中国健康受试者AAVNAb均为阳性，其顺序为AAV2>；AAV3=AAVLK03>；AAV8。AAV3及其变异体、男女受试者、不同年龄组(分别为35岁、3650岁和51岁)之间无差异。气虚体质者较平和体质者AAV8、NAB显著升高。我们的研究可能会对未来以AAV为基础的中国人群基因治疗的临床设计产生影响。
Recombinant adeno-associated virus (rAAV) serotype 2, 3 and 8 vectors are the most promising livertropic AAV serotype vectors. Liver diseases are significant problems in China. However, to date, few studies on AAV neutralizing antibodies (Nabs) were working with the Chinese population or with the rAAV3 vectors. The present study aimed to determine the prevalence of Nabs in Chinese population against wild-type AAV2, AAV3 and AAV8 capsids as well as additional two AAV3 variants. In addition, we performed a preliminary analysis to investigate the potential influence of traditional Chinese medicine body constitutions on AAV Nabs. Our work demonstrated that the majority of healthy Chinese subjects were positive for AAV Nabs, with the order of AAV2 > AAV3 = AAVLK03 > AAV8. There was no difference between: 1) AAV3 and its variants; 2) male and female subjects; and 3) different age cohorts (= 35, 3650, and = 51 years old). People in the Qi-deficiency constitution had significantly increased AAV8 Nabs than people in the Gentleness constitution. Our studies may have impact on the future clinical design of AAV-based gene therapy in the Chinese population.