Adenovirus Serotype 5-Specific Neutralizing Antibodies Target Multiple Hexon Hypervariable Regions
Adenovirus Serotype 5-Specific Neutralizing Antibodies Target Multiple Hexon Hypervariable Regions
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DOI：
10.1128/jvi.06165-11
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发表时间：
2012-01-01
影响因子：
5.4
通讯作者：
Barouch, Dan H.
中科院分区：
文献类型：
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作者：
Bradley, Ritu R.;Maxfield, Lori F.;Barouch, Dan H.
腺病毒血清型5 （Ad5）载体的免疫原性已被主要针对六邻体高变区（HVRs）的中和抗体（nab）所抑制。我们之前报道，用罕见的血清型病毒Ad48替换所有7种HVRs，产生嵌合的Ad5HVR48（1-7）载体，该载体在很大程度上逃避了小鼠和恒河猴先前存在的Ad5免疫。在这项研究中，我们评估了ad5特异性nab针对各种hvr的程度。我们构建了部分hvr -嵌合的Ad5载体，仅交换了一小部分hvr，我们将这些载体用于NAb检测和小鼠免疫原性研究，无论是否具有基线Ad5免疫。我们的研究结果表明，ad5特异性nab靶向多种hvr，这表明需要替换所有hvr来优化抗ad5免疫的规避。这些数据对开发疫苗和基因治疗的新载体具有重要意义。
The immunogenicity of adenovirus serotype 5 (Ad5) vectors has been shown to be suppressed by neutralizing antibodies (NAbs) directed primarily against the hexon hypervariable regions (HVRs). We previously reported that replacing all seven HVRs with those from the rare serotype virus Ad48 resulted in a chimeric Ad5HVR48(1-7) vector that largely evaded preexisting Ad5 immunity in mice and rhesus monkeys. In this study, we evaluated the extent to which Ad5-specific NAbs are directed against various HVRs. We constructed partial HVR-chimeric Ad5 vectors with only a subset of HVRs exchanged, and we utilized these vectors in both NAb assays and murine immunogenicity studies with and without baseline Ad5 immunity. Our results demonstrate that Ad5-specific NAbs target multiple HVRs, suggesting that replacing all HVRs is required to optimize evasion of anti-Ad5 immunity. These data have important implications for the development of novel vectors for both vaccines and gene therapy.