The Jenner Institute, University of Oxford, Oxford, United Kingdom.
PLoS One. 2012;7(7):e40385. doi: 10.1371/journal.pone.0040385. Epub 2012 Jul 13.
Recombinant adenoviruses are among the most promising tools for vaccine antigen delivery. Recently, the development of new vectors has focused on serotypes to which the human population is less exposed in order to circumvent pre-existing anti vector immunity. This study describes the derivation of a new vaccine vector based on a chimpanzee adenovirus, Y25, together with a comparative assessment of its potential to elicit transgene product specific immune responses in mice. The vector was constructed in a bacterial artificial chromosome to facilitate genetic manipulation of genomic clones. In order to conduct a fair head-to-head immunological comparison of multiple adenoviral vectors, we optimised a method for accurate determination of infectious titre, since this parameter exhibits profound natural variability and can confound immunogenicity studies when doses are based on viral particle estimation. Cellular immunogenicity of recombinant E1 E3-deleted vector ChAdY25 was comparable to that of other species E derived chimpanzee adenovirus vectors including ChAd63, the first simian adenovirus vector to enter clinical trials in humans. Furthermore, the prevalence of virus neutralizing antibodies (titre >1:200) against ChAdY25 in serum samples collected from two human populations in the UK and Gambia was particularly low compared to published data for other chimpanzee adenoviruses. These findings support the continued development of new chimpanzee adenovirus vectors, including ChAdY25, for clinical use.
重组腺病毒是最有前途的疫苗抗原传递工具之一。最近，新载体的开发重点是针对人群中暴露较少的血清型，以规避预先存在的抗载体免疫。本研究描述了一种基于黑猩猩腺病毒 Y25 的新型疫苗载体的衍生，并对其在小鼠中引发转基因产物特异性免疫反应的潜力进行了比较评估。该载体在细菌人工染色体中构建，以方便基因组克隆的遗传操作。为了对多种腺病毒载体进行公平的头对头免疫学比较，我们优化了一种准确确定感染性滴度的方法，因为该参数表现出深刻的自然变异性，并且当剂量基于病毒粒子估计时，可能会混淆免疫原性研究。重组 E1 E3 缺失载体 ChAdY25 的细胞免疫原性与其他物种 E 衍生的黑猩猩腺病毒载体（包括 ChAd63）相当，ChAd63 是第一个进入人体临床试验的灵长类腺病毒载体。此外，与其他黑猩猩腺病毒的已发表数据相比，在从英国和冈比亚的两个人群中收集的血清样本中，针对 ChAdY25 的病毒中和抗体（滴度>1:200）的流行率特别低。这些发现支持继续开发新的黑猩猩腺病毒载体，包括 ChAdY25，用于临床应用。
