Lockey Timothy D, Zhan Xiaoyan, Surman Sherri, Sample Clare E, Hurwitz Julia L
Department of Immunology, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105, USA.
Front Biosci. 2008 May 1;13:5916-27. doi: 10.2741/3126.
Epstein-Barr Virus (EBV) is the causative agent of acute infectious mononucleosis and associates with malignancies such as Burkitt lymphoma, nasopharyngeal carcinoma, and non-Hodgkin's lymphoma. Additionally, EBV is responsible for B-lymphoproliferative disease in the context of HIV-infection, genetic immunodeficiencies and organ/stem-cell transplantation. Here we discuss past and current efforts to design an EBV vaccine. We further describe preliminary studies of a novel cocktail vaccine expressing both lytic and latent EBV proteins. Specifically, a tetrameric vaccinia virus (VV) -based vaccine was formulated to express the EBV lytic proteins gp350 and gp110, and the latent proteins EBNA-2 and EBNA-3C. In a proof-of-concept study, mice were vaccinated with the individual or mixed VV. Each of the passenger genes was expressed in vivo at levels sufficient to elicit binding antibody responses. Neutralizing gp350-specific antibodies were also elicited, as were EBV-specific T-cell responses, following inoculation of mice with the single or mixed VV. Results encourage further development of the cocktail vaccine strategy as a potentially powerful weapon against EBV infection and disease in humans.
爱泼斯坦-巴尔病毒（EBV）是急性传染性单核细胞增多症的病原体，并与伯基特淋巴瘤、鼻咽癌和非霍奇金淋巴瘤等恶性肿瘤相关。此外，EBV在HIV感染、遗传性免疫缺陷以及器官/干细胞移植的情况下会引发B淋巴细胞增殖性疾病。在此，我们讨论过去和当前设计EBV疫苗的努力。我们进一步描述了一种表达裂解性和潜伏性EBV蛋白的新型联合疫苗的初步研究。具体而言，构建了一种基于四聚体痘苗病毒（VV）的疫苗，用于表达EBV裂解蛋白gp350和gp110，以及潜伏蛋白EBNA-2和EBNA-3C。在一项概念验证研究中，用单独的或混合的VV对小鼠进行接种。每个外源基因在体内的表达水平足以引发结合抗体反应。在用单一或混合VV接种小鼠后，还引发了中和性gp350特异性抗体以及EBV特异性T细胞反应。这些结果鼓励进一步开发联合疫苗策略，作为对抗人类EBV感染和疾病的潜在有力武器。
