Seroprevalence of Human Adenovirus Type 5 Neutralizing Antibody in Common Marmosets Determined by a New Set of Two Assays
Seroprevalence of Human Adenovirus Type 5 Neutralizing Antibody in Common Marmosets Determined by a New Set of Two Assays
复制标题
通过一组新的两项测定确定普通狨猴中人类 5 型腺病毒中和抗体的血清阳性率
DOI：
10.1089/vim.2019.0054
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发表时间：
2019-08-21
期刊：
影响因子：
2.2
通讯作者：
Li, Tingting
中科院分区：
文献类型：
--
作者：
Wang, Qi;Sun, Yachun;Li, Tingting
预先存在的针对人腺病毒血清型5（AdHu 5）的中和抗体（NAb）可以降低基于AdHu 5载体的疫苗的免疫原性，从而抑制宿主的免疫反应和其他同源载体的利用。普通绒猴（Callithrix jacchus）是一种新大陆小型灵长类动物，因其作为疫苗开发的临床前研究模型的潜力而引起了相当大的关注。然而，在中国饲养的普通绒猴中抗AdHu 5 NAb活性的流行率仍然未知。构建表达荧光素酶和Zs绿色报告基因的重组腺病毒载体，用流式细胞术（FCM）和化学发光法（CL）检测NAb。25只绒猴中有5只（20%）可通过FCM检测到AdHu 5 NAb。4只动物的滴度较低（1/16），而第5只动物达到1/64。CL法检测25只绒猴中有7只（28%）为抗AdHu 5 NAb阳性。4只动物（其中2只为FCM阴性）也具有低滴度NAb（1/16），表明低水平下的测定差异。2只绒猴的CL滴度为1/32，FCM滴度为1/16。一只动物在两种试验中均显示出高滴度（CL和FCM分别为1/128和1/64）。该方法简便、灵敏、准确、稳定。绒猴中预先存在的抗AdHu 5 NAb的低流行率为使用绒猴作为疫苗开发的临床前研究模型的可行性和适用性提供了重要的背景信息。
Preexisting neutralizing antibody (NAb) against human adenovirus serotype 5 (AdHu5) can reduce the immunogenicity of AdHu5 vector-based vaccine, thus inhibiting the host's immune response and utility of other homologous vectors. Common marmoset (Callithrix jacchus), a small new world primate, has attracted considerable attention for its potential as a preclinical research model of vaccine development. However, the prevalence of anti-AdHu5 NAb activity in common marmosets bred in China remains unknown. A recombinant adenovirus expressing luciferase and Zs Green reporter genes were constructed to detect NAb against rAdHu5 by flow cytometry (FCM) and chemiluminescence (CL) assay. Five of 25 marmosets (20%) presented AdHu5 NAb detectable by FCM. Four animals had low titer (1/16), while the fifth one reached 1/64. While by CL assay, 7 of 25 (28%) marmosets were anti-AdHu5 NAb positive. Four animals, two of whom were negative by FCM, also had low titer NAb (1/16), suggesting assay discrepancy at low levels. Two marmosets, 1/32 titer by CL, were at 1/16 by FCM. A single animal showed a high titer with both assays (1/128 and 1/64 by CL and FCM, respectively). The CL method was simpler, more sensitive, accurate, and stable. The low prevalence of preexisting anti-AdHu5 NAb in marmosets provides important background information on the feasibility and applicability of using marmosets as a preclinical research model for vaccine development.