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首页> 外文期刊>Vaccine >Immunogenicity and performance of an enterovirus 71 virus-like-particle vaccine in nonhuman primates
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Immunogenicity and performance of an enterovirus 71 virus-like-particle vaccine in nonhuman primates

机译：肠道病毒71病毒样颗粒疫苗在非人类灵长类动物中的免疫原性和性能

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摘要

A vaccine against human enterovirus 71 (EV-A71) is urgently needed to combat outbreaks of EV-A71 and in particular, the serious neurological complications that manifest during these outbreaks. In this study, an EV-A71 virus-like-particle (VLP) based on a B5 subgenogroup (EV-A71-B5 VLP) was generated using an insect cell/baculovirus platform. Biochemical analysis demonstrated that the purified VLP had a highly native procapsid structure and initial studies in vivo demonstrated that the VLPs were immunogenic in mice. The impact of VLP immunization on infection was examined in non-human primates using a VLP prime-boost strategy prior to EV-A71 challenge. Rhesus macaques were immunized on day 0 and day 21 with VLPs (100 mu g/dose) containing adjuvant or with adjuvant alone (controls), and were challenged with EV-A71 on day 42. Complete blood counts, serum chemistry, magnetic resonance imaging (MRI) scans, and histopathology results were mostly normal in vaccinated and control animals after virus challenge demonstrating that the fatal EV-A71-B3 clinical isolate used in this study was not highly virulent in rhesus macaques. Viral genome and/or infectious virus were detected in blood, spleen or brain of two of three control animals, but not in any specimens from the vaccinated animals, indicating that VLP immunization prevented systemic spread of EV-A71 in rhesus macaques. High levels of IgM and IgG were detected in VLP-vaccinated animals and these responses were highly specific for EV-A71 particles and capsid proteins. Serum from vaccinated animals also exhibited similar neutralizing activity against different subgenogroups of EV-A71 demonstrating that the VLPs induced cross-neutralizing antibodies. In conclusion, our EV-A71-B5 VLP is safe, highly immunogenic, and prevents systemic EV-A71-B3 infection in nonhuman primates making it a viable attractive vaccine candidate for EV-A71. (C) 2015 Elsevier Ltd. All rights reserved.
机译：迫切需要一种针对人类肠道病毒71的疫苗（EV-A71），以抗击EV-A71的爆发，尤其是应对这些爆发期间表现出的严重神经系统并发症。在这项研究中，使用昆虫细胞/杆状病毒平台生成了基于B​​5亚基因组（EV-A71-B5 VLP）的EV-A71病毒样颗粒（VLP）。生化分析表明，纯化的VLP具有高度天然的前壳体结构，体内的初步研究表明VLP在小鼠中具有免疫原性。在EV-A71攻击之前，使用VLP初免-加强策略在非人灵长类动物中检查了VLP免疫对感染的影响。在第0天和第21天，用含佐剂的VLP（100μg /剂量）或仅用佐剂（对照）免疫恒河猴，并在第42天用EV-A71免疫猕猴。全血细胞计数，血清化学，磁共振成像（MRI）扫描和病毒攻击后，接种疫苗的动物和对照动物的病理结果大部分正常，这表明该研究中使用的致命EV-A71-B3临床分离株在猕猴中没有高毒力。在三只对照动物中的两只动物的血液，脾脏或大脑中检测到病毒基因组和/或感染性病毒，但在接种动物的任何标本中均未检测到，这表明VLP免疫阻止了EV-A71在猕猴中的全身扩散。在接种VLP的动物中检测到高水平的IgM和IgG，这些反应对EV-A71颗粒和衣壳蛋白高度特异性。接种动物的血清对EV-A71的不同亚基因组也显示出相似的中和活性，表明VLP诱导了交叉中和抗体。总之，我们的EV-A71-B5 VLP是安全的，高度免疫原性的，可防止非人灵长类动物全身性EV-A71-B3感染，使其成为EV-A71可行的有吸引力的候选疫苗。 （C）2015 Elsevier Ltd.保留所有权利。

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