Research Unit Gene Vectors, Helmholtz Zentrum München, Marchioninistr. 25, D-81377 Munich, Germany.
J Virol. 2011 Dec;85(24):13105-13. doi: 10.1128/JVI.05598-11. Epub 2011 Oct 12.
Epstein-Barr Virus (EBV) is an ubiquitous human herpesvirus which can lead to infectious mononucleosis and different cancers. In immunocompromised individuals, this virus is a major cause for morbidity and mortality. Transplant patients who did not encounter EBV prior to immunosuppression frequently develop EBV-associated malignancies, but a prophylactic EBV vaccination might reduce this risk considerably. Virus-like particles (VLPs) mimic the structure of the parental virus but lack the viral genome. Therefore, VLPs are considered safe and efficient vaccine candidates. We engineered a dedicated producer cell line for EBV-derived VLPs. This cell line contains a genetically modified EBV genome which is devoid of all potential viral oncogenes but provides viral proteins essential for the assembly and release of VLPs via the endosomal sorting complex required for transport (ESCRT). Human B cells readily take up EBV-based VLPs and present viral epitopes in association with HLA molecules to T cells. Consequently, EBV-based VLPs are highly immunogenic and elicit humoral and strong CD8+ and CD4+ T cell responses in vitro and in a preclinical murine model in vivo. Our findings suggest that VLP formulations might be attractive candidates to develop a safe and effective polyvalent vaccine against EBV.
EB 病毒（EBV）是一种普遍存在的人类疱疹病毒，可导致传染性单核细胞增多症和不同的癌症。在免疫功能低下的个体中，这种病毒是发病率和死亡率的主要原因。在免疫抑制之前未接触过 EBV 的移植患者经常会发生 EBV 相关恶性肿瘤，但预防性 EBV 疫苗接种可能会大大降低这种风险。病毒样颗粒（VLPs）模拟亲本病毒的结构，但缺乏病毒基因组。因此，VLPs 被认为是安全有效的疫苗候选物。我们为 EBV 衍生的 VLPs 工程设计了专用的生产细胞系。该细胞系包含经过基因修饰的 EBV 基因组，该基因组缺乏所有潜在的病毒致癌基因，但提供了组装和释放 VLPs 所必需的病毒蛋白，这是通过内体分选复合物所必需的运输（ESCRT）。人类 B 细胞很容易摄取 EBV 基 VLPs，并与 HLA 分子一起呈递病毒表位给 T 细胞。因此，EBV 基 VLPs 具有高度的免疫原性，并在体外和临床前小鼠模型中诱导体液和强烈的 CD8+和 CD4+T 细胞反应。我们的研究结果表明，VLPs 制剂可能是开发针对 EBV 的安全有效的多价疫苗的有吸引力的候选物。
