关键词: adenoviral immunity adenoviral vaccine adenoviral vector neutralizing antibodies

来  源:   DOI:10.3390/vaccines12020155   PDF(Pubmed)

Abstract:
Adenoviral vectors based on the human adenovirus species C serotype 5 (HAdV-C5) are commonly used for vector-based gene therapies and vaccines. In the preclinical stages of development, their safety and efficacy are often validated in suitable animal models. However, pre-existing neutralizing antibodies may severely influence study outcomes. Here, we generated a new HAdV-C5-based reporter vector and established a high-throughput screening assay for the multivalent detection of HAdV-C5-neutralizing antibodies in serum. We screened the sera of rhesus macaques at different primate centers, and of rabbits, horses, cats, and dogs, showing that HAdV-C5-neutralizing antibodies can be found in all species, albeit at different frequencies. Our results emphasize the need to prescreen model animals in HAdV-C5-based studies.
摘要:
基于人腺病毒种类C血清型5(HAdV-C5)的腺病毒载体通常用于基于载体的基因疗法和疫苗。在发展的临床前阶段,它们的安全性和有效性通常在合适的动物模型中得到验证.然而,预先存在的中和抗体可能严重影响研究结果.这里,我们产生了一种新的基于HAdV-C5的报告载体,并建立了用于多价检测血清中HAdV-C5中和抗体的高通量筛选试验.我们在不同的灵长类动物中心筛选了恒河猴的血清,还有兔子,马,猫,还有狗,表明HAdV-C5中和抗体可以在所有物种中发现,尽管频率不同。我们的结果强调了在基于HAdV-C5的研究中需要预先筛选模型动物。
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