Department of Cell Biology, National Institutes for Food and Drug Control, Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, Beijing, China.
J Med Virol. 2013 Sep;85(9):1550-6. doi: 10.1002/jmv.23647.
Recombinant adeno-associated virus serotype 1 (AAV1) has attracted tremendous interest as a promising vector for gene therapy and vaccine applications. However, the presence of AAV1 neutralizing antibodies as a consequence of exposure to wild type AAV1 can limit significantly effective gene transfer for biologics based AAV1 vector. Prior studies have reported that a prevalence of AAV1 neutralizing antibodies ranged from 10% to 50% in different countries around the world, and up to 79% in Dutch subjects. However, few studies have reported on the AAV1 neutralizing antibody prevalence in Chinese subjects. In this study, a high-throughput luciferase-based virus neutralization assay was established and standardized for critical parameters, including the appropriate cell line, and the optimal viral infection dose, and the infection time with homologous AAV1 vaccinated mice and guinea pig sera. Then, a total of 500 healthy individual serum samples from two separate regions of China were screened for the AAV1 neutralizing antibodies by conducting a non-randomized, cross-sectional analysis. Interestingly, a high prevalence of AAV1 neutralizing antibody (69.8%) was found in all individuals. There was significant difference observed for prevalence by gender (P = 0.042), age range (P = 0.011) and geographic origin (P < 0.001). The percentage of positive AAV1 neutralizing antibodies (NT50 > 10) in teenagers (year <18, as of 2012) was significant lower than that of adults (19-56, as of 2012) (P = 0.011), indicating the optimal vaccination period of childhood. The current study provides a useful insight for the future development of AAV1-based vaccination and gene therapy strategies in Beijing and Anhui provinces of China.
重组腺相关病毒血清型 1（AAV1）作为基因治疗和疫苗应用的一种很有前途的载体，引起了极大的兴趣。然而，由于暴露于野生型 AAV1，存在 AAV1 中和抗体，会显著限制基于生物制品的 AAV1 载体的有效基因转移。先前的研究报告称，在世界各地不同的国家，AAV1 中和抗体的流行率为 10%至 50%，在荷兰人群中高达 79%。然而，很少有研究报告中国人群中的 AAV1 中和抗体流行率。在这项研究中，建立了一种基于荧光素酶的高通量病毒中和测定法，并对关键参数进行了标准化，包括适当的细胞系和最佳病毒感染剂量，以及同源 AAV1 接种小鼠和豚鼠血清的感染时间。然后，通过进行非随机、横断面分析，对来自中国两个不同地区的 500 名健康个体血清样本进行了 AAV1 中和抗体的筛查。有趣的是，在所有个体中均发现 AAV1 中和抗体的高流行率（69.8%）。按性别（P=0.042）、年龄范围（P=0.011）和地理位置（P<0.001）观察到中和抗体的流行率存在显著差异。青少年（2012 年时年龄<18 岁）中 AAV1 中和抗体（NT50>10）的阳性率显著低于成年人（19-56 岁，2012 年）（P=0.011），提示儿童时期是最佳的接种期。本研究为中国北京和安徽地区未来基于 AAV1 的疫苗接种和基因治疗策略的发展提供了有用的见解。
