The need and challenges for development of an Epstein-Barr virus vaccine.
The need and challenges for development of an Epstein-Barr virus vaccine.
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DOI：
10.1016/j.vaccine.2012.09.041
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发表时间：
2013-04-18
期刊：
影响因子：
5.5
通讯作者：
Nabel, Gary J.
中科院分区：
文献类型：
--
作者：
Cohen, Jeffrey I.;Mocarski, Edward S.;Raab-Traub, Nancy;Corey, Lawrence;Nabel, Gary J.
关键词：
EB病毒（Epstein-Barr virus，EBV）是引起传染性单核细胞增多症的主要原因，与鼻咽癌、胃癌、霍奇金淋巴瘤、伯基特淋巴瘤、器官或干细胞移植后淋巴瘤等多种恶性肿瘤有关。含可溶性EBV糖蛋白gp 350的候选疫苗在用EBV攻击后保护棉顶绢毛猴免受EBV淋巴瘤的侵袭。在人类EBV疫苗的唯一2期试验中，明矾中的可溶性gp 350和单磷酰脂质A佐剂降低了EBV血清阴性成人中传染性单核细胞增多症的发生率，但不影响EBV感染的发生率。已经在少数成人中测试了对应于EBV潜伏蛋白的肽疫苗以预防传染性单核细胞增多症。开发EBV疫苗的一些障碍包括（a）除了gp 350之外的另外的病毒蛋白质对于预防单核细胞增多症或EBV恶性肿瘤是否更有效，（B）在缺乏肿瘤发展的良好替代标志物的情况下进行预防EBV相关恶性肿瘤的临床试验的困难，以及原发性EBV感染和许多EBV肿瘤的发展之间的长时间段，（c）缺乏对预防EBV感染和疾病的免疫相关性的了解，（d）研究预防EBV感染和疾病的动物模型的局限性，和（e）需要关于传染性单核细胞增多症的经济和社会负担的额外信息，以评估预防性疫苗的成本效益。
Epstein-Barr virus (EBV) is the major cause of infectious mononucleosis and is associated with several malignancies including nasopharyngeal carcinoma, gastric carcinoma, Hodgkin lymphoma, Burkitt lymphoma, and lymphoma after organ or stem cell transplant. A candidate vaccine containing soluble EBV glycoprotein gp350 protected cottontop tamarins from EBV lymphoma after challenge with EBV. In the only phase 2 trial of an EBV vaccine in humans, soluble gp350 in alum and monophosphoryl lipid A adjuvant reduced the rate of infectious mononucleosis in EBV seronegative adults, but did not affect the rate of EBV infection. A peptide vaccine corresponding to EBV latency proteins has been tested in a small number of adults to prevent infectious mononucleosis. Some of the barriers to development of an EBV vaccine include (a) whether additional viral proteins in addition to gp350 would be more effective for preventing mononucleosis or EBV malignancies, (b) the difficulty of performing clinical trials to prevent EBV associated malignancies in the absence of good surrogate markers for tumor development, and the long period of time between primary EBV infection and development of many EBV tumors, (c) the lack of knowledge of immune correlates for protection against EBV infection and disease, (d) the limitations in animal models to study protection against EBV infection and disease, and (e) the need for additional information on the economic and societal burden of infectious mononucleosis to assess the cost-benefit of a prophylactic vaccine.
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