PROTECTIVE IMMUNIZATION AGAINST EPSTEIN-BARR VIRUS-INDUCED DISEASE IN COTTONTOP TAMARINS USING THE VIRUS ENVELOPE GLYCOPROTEIN GP340 PRODUCED FROM A BOVINE PAPILLOMAVIRUS EXPRESSION VECTOR
PROTECTIVE IMMUNIZATION AGAINST EPSTEIN-BARR VIRUS-INDUCED DISEASE IN COTTONTOP TAMARINS USING THE VIRUS ENVELOPE GLYCOPROTEIN GP340 PRODUCED FROM A BOVINE PAPILLOMAVIRUS EXPRESSION VECTOR
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DOI：
10.1099/0022-1317-73-2-449
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发表时间：
1992-02-01
影响因子：
3.8
通讯作者：
MORGAN, AJ
中科院分区：
文献类型：
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作者：
FINERTY, S;TARLTON, J;MORGAN, AJ
接种EB病毒（EBV）可诱导棉顶绒猴（Saguinus oedipus oedipus）发生恶性淋巴瘤。这提供了用于评估候选EBV疫苗的功效的实验动物模型，所述候选EBV疫苗旨在降低与EBV感染相关的人类肿瘤的发生率。以前的工作表明，实验疫苗的基础上制备的主要病毒包膜糖蛋白gp340从EBV感染的细胞膜是有效的，在保护棉顶绢毛猴对EBV诱导的疾病。然而，并不是所有的纯化gp340制剂诱导对EBV淋巴瘤的绢毛猴的保护性免疫。在这项工作中，棉顶绢毛猴免疫重组gp340，使用牛乳头瘤病毒（BPV）表达载体，和苏氨酰胞壁酰二肽佐剂配方。虽然重组衍生的gp340缺乏真正的gp340的膜锚序列，并在小鼠细胞中表达，但它具有免疫原性并诱导病毒中和抗体。健康的接种疫苗的绢毛猴对EBV诱导的疾病有保护作用。重组gp340产物能够在棉顶绢毛猴中引发保护性免疫的证明是EBV疫苗开发中的重要一步，因为以前不清楚重组产物是否具有确切的三级结构，包括必要的碳水化合物组分，以诱导保护性免疫。重组gp340疫苗与通过费力的生物化学分离生产真实分子相比具有多种优点，包括成本较低和不存在潜在致癌的EBV DNA。因此，使用BPV表达载体产生的重组gp340适合于开发为用于人I期试验及以后的候选EBV疫苗。
Inoculation with Epstein-Barr virus (EBV) induces malignant lymphomas in the cottontop tamarin (Saguinus oedipus oedipus). This provides an experimental animal model for assessing the efficacy of candidate EBV vaccines which are intended to reduce the incidence of human tumours associated with EBV infection. Previous work has shown that experimental vaccines based on the major virus envelope glycoprotein gp340 prepared from the membranes of EBV-infected cells are effective in protecting cottontop tamarins against EBV-induced disease. However, not all purified gp340 preparations induce protective immunity against EBV lymphoma in the tamarin. In this work, cottontop tamarins were immunized with recombinant gp340, produced using a bovine papillomavirus (BPV) expression vector, and a threonyl muramyl dipeptide adjuvant formulation. Although the recombinant-derived gp340 lacked the membrane anchor sequence of authentic gp340 and was expressed in mouse cells, it was immunogenic and induced virus-neutralizing antibodies. Healthy vaccinated tamarins were protected against EBV-induced disease. The demonstration that a recombinant gp340 product is able to elicit protective immunity in the cottontop tamarin is a significant step in the development of an EBV vaccine because previously it had not been clear whether a recombinant product would have the exact tertiary structure, including the necessary carbohydrate components, to induce protective immunity. A recombinant gp340 vaccine offers various advantages over production of the authentic molecule by laborious biochemical separation, including lower cost and the absence of potentially oncogenic EBV DNA. Therefore, recombinant gp340 produced using the BPV expression vector is suitable for development as a candidate EBV vaccine for a human Phase I trial and beyond.