Prevalence of neutralizing antibodies to adenoviral serotypes 5 and 35 in the adult populations of The Gambia, South Africa, and the United States
Prevalence of neutralizing antibodies to adenoviral serotypes 5 and 35 in the adult populations of The Gambia, South Africa, and the United States
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DOI：
10.1128/cdli.11.2.351-357.2004
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发表时间：
2004-03-01
期刊：
影响因子：
--
通讯作者：
Gambotto, A
中科院分区：
文献类型：
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作者：
Nwanegbo, E;Vardas, E;Gambotto, A
使用腺病毒作为基因治疗载体的主要限制之一是不同人群中存在预先形成的免疫。最近的研究将腺病毒基因治疗试验的失败与抗腺病毒中和抗体（NAb）的存在联系起来。了解此类抗体的分布和特异性将有助于设计成功的重组腺病毒基因疗法和疫苗。为了评估 NAb 对腺病毒血清型 5 和 35（Ad5 和 Ad35）的流行情况，我们使用中和测定分析了生活在冈比亚、南非和美国的免疫功能正常的成人个体的血清样本。将血清样本与A549肺癌细胞和编码增强型绿色或黄色荧光蛋白的腺病毒一起孵育；通过荧光显微镜和流式细胞术分析结果。使用这种技术，我们发现冈比亚、南非和美国受试者中低滴度和高滴度的针对 Ad5 的 NAb 的流行率很高。相反，所有受试者的 Ad35 NAb 患病率均较低；当存在时，抗 Ad35 NAb 的滴度较低。由于腺病毒能够引发全身和粘膜免疫反应，Ad35 及其低 NAb 流行率似乎是基因治疗应用中有吸引力的候选载体。
One of the major limitations of the use of adenoviruses as gene therapy vectors is the existence of preformed immunity in various populations. Recent studies have linked failure of adenoviral gene therapy trials to the presence of antiadenoviral neutralizing antibodies (NAb). Understanding the distribution and specificity of such antibodies will assist in the design of successful recombinant adenoviral gene therapies and vaccines. To assess the prevalence of NAb to adenovirus serotypes 5 and 35 (Ad5 and Ad35), we analyzed serum samples from adult immunocompetent individuals living in The Gambia, South Africa, and the United States by using a neutralization assay. Serum samples were incubated with A549 lung carcinoma cells and adenoviruses encoding enhanced green or yellow fluorescent proteins; results were analyzed by fluorescence microscopy and flow cytometry. Using this technique, we found a high prevalence of NAb against Ad5 in Gambian, South African, and U.S. subjects at both low and high titers. Conversely, all subjects displayed a low prevalence of NAb to Ad35; when present, anti-Ad35 NAb were seen at low titers. Because of the ability of adenoviruses to elicit systemic and mucosal immune responses, Ad35 with its low NAb prevalence appears to be an attractive candidate vector for gene therapy applications.