State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, China.
Cryo-EM Centre, Southern University of Science and Technology, Shenzhen, Guangdong Province, China.
J Virol. 2022 May 11;96(9):e0033622. doi: 10.1128/jvi.00336-22. Epub 2022 Apr 11.
Epstein-Barr virus (EBV), the first identified human tumor virus, is etiologically associated with various kinds of malignant and benign diseases, accounting for 265,000 cancer incident cases and 164,000 cancer deaths in 2017. EBV prophylactic vaccine development has been gp350 centered for several decades. However, clinical studies show that gp350-centered vaccines fail to prevent EBV infection. Advances in the EBV infection mechanisms shed light on gB and gHgL, the two key components of the infection apparatus. In this study, for the first time, we utilized recombinant vesicular stomatitis virus (VSV) to display EBV gB (VSV-ΔG-gB/gB-G) or gHgL (VSV-ΔG-gHgL). studies confirmed successful virion production and glycoprotein presentation on the virion surface. In mouse models, VSV-ΔG-gB/gB-G or VSV-ΔG-gHgL elicited potent humoral responses. Neutralizing antibodies elicited by VSV-ΔG-gB/gB-G were prone to prevent B cell infection, while those elicited by VSV-ΔG-gHgL were prone to prevent epithelial cell infection. Combinatorial vaccination yields an additive effect. The ratio of endpoint neutralizing antibody titers to the endpoint total IgG titers immunized with VSV-ΔG-gHgL was approximately 1. The ratio of IgG1/IgG2a after VSV-ΔG-gB/gB-G immunization was approximately 1 in a dose-dependent, adjuvant-independent manner. Taken together, VSV-based EBV vaccines can elicit a high ratio of epithelial and B lymphocyte neutralizing antibodies, implying their unique potential as EBV prophylactic vaccine candidates. Epstein-Barr virus (EBV), one of the most common human viruses and the first identified human oncogenic virus, accounted for 265,000 cancer incident cases and 164,000 cancer deaths in 2017 as well as millions of nonmalignant disease cases. So far, no prophylactic vaccine is available to prevent EBV infection. In this study, for the first time, we reported the VSV-based EBV vaccines presenting two key components of the EBV infection apparatus, gB and gHgL. We confirmed potent antigen-specific antibody generation; these antibodies prevented EBV from infecting epithelial cells and B cells, and the IgG1/IgG2a ratio indicated balanced humoral-cellular responses. Taken together, we suggest VSV-based EBV vaccines are potent prophylactic candidates for clinical studies and help eradicate numerous EBV-associated malignant and benign diseases.
爱泼斯坦-巴尔病毒（EBV）是第一个被鉴定的人类肿瘤病毒，与各种恶性和良性疾病在病因上有关联，占 2017 年 265,000 例癌症发病病例和 164,000 例癌症死亡病例。几十年来，一直在围绕 gp350 进行 EBV 预防性疫苗的开发。然而，临床研究表明，以 gp350 为中心的疫苗不能预防 EBV 感染。EBV 感染机制的研究进展揭示了 gB 和 gHgL，这是感染装置的两个关键组成部分。在这项研究中，我们首次利用重组水疱性口炎病毒（VSV）展示 EBV gB（VSV-ΔG-gB/gB-G）或 gHgL（VSV-ΔG-gHgL）。研究证实成功生产了病毒粒子，并在病毒粒子表面展示了糖蛋白。在小鼠模型中，VSV-ΔG-gB/gB-G 或 VSV-ΔG-gHgL 引发了强烈的体液反应。VSV-ΔG-gB/gB-G 引发的中和抗体易于预防 B 细胞感染，而 VSV-ΔG-gHgL 引发的中和抗体易于预防上皮细胞感染。组合疫苗接种具有相加效应。用 VSV-ΔG-gHgL 免疫的终点中和抗体效价与终点总 IgG 效价的比值约为 1。VSV-ΔG-gB/gB-G 免疫后 IgG1/IgG2a 的比值约为 1，呈剂量依赖性，与佐剂无关。总之，基于 VSV 的 EBV 疫苗可以引发高比例的上皮细胞和 B 淋巴细胞中和抗体，这表明它们作为 EBV 预防性疫苗候选物具有独特的潜力。
爱泼斯坦-巴尔病毒（EBV）是最常见的人类病毒之一，也是第一个被鉴定的人类致癌病毒，2017 年导致 265,000 例癌症发病病例和 164,000 例癌症死亡病例，并导致数百万例非恶性疾病病例。迄今为止，尚无预防 EBV 感染的预防性疫苗。在这项研究中，我们首次报告了基于 VSV 的 EBV 疫苗，该疫苗展示了 EBV 感染装置的两个关键组成部分，gB 和 gHgL。我们证实了强大的抗原特异性抗体生成；这些抗体阻止了 EBV 感染上皮细胞和 B 细胞，而 IgG1/IgG2a 的比值表明了平衡的体液-细胞反应。总之，我们建议基于 VSV 的 EBV 疫苗是临床研究中有效的预防性候选物，并有助于消除许多 EBV 相关的恶性和良性疾病。
