A chimeric EBV gp350/220-based VLP replicates the virion B-cell attachment mechanism and elicits long-lasting neutralizing antibodies in mice.
A chimeric EBV gp350/220-based VLP replicates the virion B-cell attachment mechanism and elicits long-lasting neutralizing antibodies in mice.
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DOI：
10.1186/s12967-015-0415-2
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发表时间：
2015-02-06
影响因子：
7.4
通讯作者：
Fingeroth JD
中科院分区：
文献类型：
--
作者：
Ogembo JG;Muraswki MR;McGinnes LW;Parcharidou A;Sutiwisesak R;Tison T;Avendano J;Agnani D;Finberg RW;Morrison TG;Fingeroth JD
爱泼斯坦-巴尔病毒（EBV）是一种致癌的γ疱疹病毒，可引起急性传染性单核细胞增多症（AIM），并与几种人类恶性肿瘤的发展有关。迫切需要一种安全、可预防感染和/或限制疾病的疫苗。在人类疱疹病毒中，糖蛋白（gp）350/220是EBV包膜上的主要配体，是高度保守的，它能启动EBV与易感宿主细胞的附着。感染需要gp350/220与b细胞上的补体受体2 (CR2)/CD21和/或(CR1)/CD35相互作用。对gp350/220的有效抗体反应在动物模型和人类中出现。因此，gp350/220为预防性亚单位疫苗的开发提供了一个有吸引力的候选物。然而，在最近的一项II期临床试验中，用可溶性重组gp350免疫可降低AIM的发生率，但不能预防感染。尽管有各种尝试生产EBV疫苗，但没有疫苗获得许可。本文描述了一种基于新型新城疫病病毒（NDV）的亚单位疫苗-病毒样颗粒（VLP）平台，该平台由EBVgp350/220外结构域与NDV融合(F)蛋白融合组成。嵌合蛋白EBVgp350/220-F被整合到由NDV基质和核蛋白组成的VLP的膜中。这些颗粒在直径和形状上与天然EBV相似，并结合CD21和CD35。体外评估时，EBVgp350/220-F VLPs免疫BALB/c小鼠可引起强烈、持久的中和抗体反应。该嵌合VLP使用不含人类核酸和ebv转化基因的平台在中国仓鼠卵巢（CHO）细胞中高效生产，预计具有优越的安全性。
Epstein-Barr virus (EBV), an oncogenic gammaherpesvirus, causes acute infectious mononucleosis (AIM) and is linked to the development of several human malignancies. There is an urgent need for a vaccine that is safe, prevents infection and/or limits disease. Unique among human herpesviruses, glycoprotein (gp)350/220, which initiates EBV attachment to susceptible host cells, is the major ligand on the EBV envelope and is highly conserved. Interaction between gp350/220 and complement receptor type 2 (CR2)/CD21 and/or (CR1)/CD35 on B-cells is required for infection. Potent antibody responses to gp350/220 occur in animal models and humans. Thus, gp350/220 provides an attractive candidate for prophylactic subunit vaccine development. However, in a recent Phase II clinical trial immunization with soluble recombinant gp350 reduced the incidence of AIM, but did not prevent infection. Despite various attempts to produce an EBV vaccine, no vaccine is licensed. Herein we describe a sub-unit vaccine against EBV based on a novel Newcastle disease virus (NDV)-virus-like particle (VLP) platform consisting of EBVgp350/220 ectodomain fused to NDV-fusion (F) protein. The chimeric protein EBVgp350/220-F is incorporated into the membrane of a VLP composed of the NDV matrix and nucleoprotein. The particles resemble native EBV in diameter and shape and bind CD21 and CD35. Immunization of BALB/c mice with EBVgp350/220-F VLPs elicited strong, long-lasting neutralizing antibody responses when assessed in vitro. This chimeric VLP is predicted to provide a superior safety profile as it is efficiently produced in Chinese hamster ovary (CHO) cells using a platform devoid of human nucleic acid and EBV-transforming genes.
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影响因子：
5.4
作者：
Braun, Marion;Jandus, Camilla;Romero, Pedro
通讯作者：
Romero, Pedro
影响因子：
11.4
作者：
BIGGIN, M;FARRELL, PJ;BARRELL, BG
通讯作者：
BARRELL, BG
影响因子：
5.4
作者：
Henson, Brandon W.;Perkins, Edward M.;Desai, Prashant
通讯作者：
Desai, Prashant
稳定的细胞种群的产生和表征以诱导方式释放基于HIV-1的病毒（如颗粒）。
影响因子：
3.5
作者：
Muratori, Claudia;D'Aloja, Paola;Superti, Fabiana;Tinari, Antonella;Sol-Foulon, Nathalie;Sparacio, Sandra;Bosch, Valerie;Schwartz, Olivier;Federico, Maurizio
通讯作者：
Federico, Maurizio
影响因子：
6.4
作者：
Balfour, Henry H., Jr.;Odumade, Oludare A.;Hogquist, Kristin A.
通讯作者：
Hogquist, Kristin A.