A high infectious simian adenovirus type 23 vector based vaccine efficiently protects common marmosets against Zika virus infection
A high infectious simian adenovirus type 23 vector based vaccine efficiently protects common marmosets against Zika virus infection
复制标题
基于高传染性猿猴腺病毒 23 型载体的疫苗可有效保护普通狨猴免受寨卡病毒感染
DOI：
10.1371/journal.pntd.0008027
复制
发表时间：
2020-02-01
影响因子：
3.8
通讯作者：
Li, Chengyao
中科院分区：
文献类型：
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作者：
Luo, Shengxue;Zhao, Wei;Li, Chengyao
寨卡病毒 (ZIKV) 已在许多国家或地区传播，导致严重的神经系统并发症，并可能致命。小型灵长类普通狨猴很容易感染寨卡病毒，这与人类感染的主要特征相似。在此，生产了一种新型猿猴腺病毒 23 型载体疫苗，表达 ZIKV 前膜包膜蛋白 (Sad23L-prM-E)，具有高感染滴度。由于确定了小鼠的免疫原性，将单剂量的3x10(8) PFU Sad23L-prM-E疫苗肌肉注射给狨猴。该疫苗提高了 10(4.07) E 特异性抗体和 10(3.13) 中和抗体 (NAb) 的抗体滴度，以及对 E 肽的强烈特异性 IFN-γ 分泌 T 细胞反应（1,219 个 SFC/10(6) 细胞）。接种疫苗的狨猴在初次免疫后六周接受高剂量 ZIKV (10(5) PFU) 攻击后，病毒血症减少了 100 倍以上，并且在接触 ZIKV 后 1-2 周获得了低水平的可检测病毒 RNA (10(3.66)) 和 T 细胞反应 (>726 SFC/10(6) PBMC)，而未接种疫苗的对照狨猴产生了长期高滴度的 ZIKV（10(5.73) 拷贝/ml）（P
Zika virus (ZIKV) has spread in many countries or territories causing severe neurologic complications with potential fatal outcomes. The small primate common marmosets are susceptible to ZIKV, mimicking key features of human infection. Here, a novel simian adenovirus type 23 vector-based vaccine expressing ZIKV pre-membrane-envelope proteins (Sad23L-prM-E) was produced in high infectious titer. Due to determination of immunogenicity in mice, a single-dose of 3x10(8) PFU Sad23L-prM-E vaccine was intramuscularly inoculated to marmosets. This vaccine raised antibody titers of 10(4.07) E-specific and 10(3.13) neutralizing antibody (NAb), as well as robust specific IFN-gamma secreting T-cell response (1,219 SFCs/10(6) cells) to E peptides. The vaccinated marmosets, upon challenge with a high dose of ZIKV (10(5) PFU) six weeks post prime immunization, reduced viremia by more than 100 folds, and the low level of detectable viral RNA (10(3.66)) and T-cell response (>726 SFCs/10(6) PBMCs) were acquired 1-2 weeks post exposure to ZIKV, while non-vaccinated control marmosets developed long-term high titer of ZIKV (10(5.73) copies/ml) (P