四十年预防性 EBV 疫苗研究：系统回顾与历史透视。
Four Decades of Prophylactic EBV Vaccine Research: A Systematic Review and Historical Perspective.
机构信息
Irell & Manella Graduate School of Biological Sciences of City of Hope, Duarte, CA, United States.
Department of Immuno-Oncology, Beckman Research Institute of City of Hope, Duarte, CA, United States.
出版信息
Front Immunol. 2022 Apr 14;13:867918. doi: 10.3389/fimmu.2022.867918. eCollection 2022.
BACKGROUND
Epstein-Barr virus (EBV) is the causal agent of infectious mononucleosis and has been associated with various cancers and autoimmune diseases. Despite decades of research efforts to combat this major global health burden, there is no approved prophylactic vaccine against EBV. To facilitate the rational design and assessment of an effective vaccine, we systematically reviewed pre-clinical and clinical prophylactic EBV vaccine studies to determine the antigens, delivery platforms, and animal models used in these studies.
METHODS
We searched Cochrane Library, ClinicalTrials.gov, Embase, PubMed, Scopus, Web of Science, WHO's Global Index Medicus, and Google Scholar from inception to June 20, 2020, for EBV prophylactic vaccine studies focused on humoral immunity.
RESULTS
The search yielded 5,614 unique studies. 36 pre-clinical and 4 clinical studies were included in the analysis after screening against the exclusion criteria. In pre-clinical studies, gp350 was the most commonly used immunogen (33 studies), vaccines were most commonly delivered as monomeric proteins (12 studies), and mice were the most used animal model to test immunogenicity (15 studies). According to an adaptation of the CAMARADES checklist, 4 pre-clinical studies were rated as very high, 5 as high, 13 as moderate quality, 11 as poor, and 3 as very poor. In clinical studies, gp350 was the sole vaccine antigen, delivered in a vaccinia platform (1 study) or as a monomeric protein (3 studies). The present study was registered in PROSPERO (CRD42020198440).
CONCLUSIONS
Four major obstacles have prevented the development of an effective prophylactic EBV vaccine: undefined correlates of immune protection, lack of knowledge regarding the ideal EBV antigen(s) for vaccination, lack of an appropriate animal model to test vaccine efficacy, and lack of knowledge regarding the ideal vaccine delivery platform. Our analysis supports a multivalent antigenic approach including two or more of the five main glycoproteins involved in viral entry (gp350, gB, gH/gL, gp42) and a multimeric approach to present these antigens. We anticipate that the application of two underused challenge models, rhesus macaques susceptible to rhesus lymphocryptovirus (an EBV homolog) and common marmosets, will permit the establishment of correlates of immune protection and attainment of more generalizable data.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=198440, identifier PROSPERO I.D. CRD4202019844.
背景
EB 病毒（EBV）是传染性单核细胞增多症的病原体，与各种癌症和自身免疫性疾病有关。尽管几十年来一直在努力研究对抗这一主要的全球健康负担，但仍没有批准用于预防 EBV 的疫苗。为了促进有效疫苗的合理设计和评估，我们系统地回顾了预防 EBV 的临床前和临床疫苗研究，以确定这些研究中使用的抗原、输送平台和动物模型。
方法
我们从 2020 年 6 月 20 日之前在 Cochrane Library、ClinicalTrials.gov、Embase、PubMed、Scopus、Web of Science、世界卫生组织全球医学索引和 Google Scholar 中搜索了以体液免疫为重点的预防 EBV 疫苗研究。
结果
搜索产生了 5614 个独特的研究。经过排除标准筛选后，有 36 项临床前研究和 4 项临床研究被纳入分析。在临床前研究中，gp350 是最常用的免疫原（33 项研究），疫苗最常作为单体蛋白（12 项研究）递送，小鼠是最常用于测试免疫原性的动物模型（15 项研究）。根据 CAMARADES 清单的改编版，4 项临床前研究被评为非常高，5 项为高，13 项为中等质量，11 项为差，3 项为非常差。在临床研究中，gp350 是唯一的疫苗抗原，以痘苗平台（1 项研究）或单体蛋白（3 项研究）递送。本研究已在 PROSPERO（CRD42020198440）注册。
结论
有四个主要障碍阻止了有效预防 EBV 疫苗的开发：免疫保护的相关因素尚未确定、缺乏用于疫苗接种的理想 EBV 抗原（s）的知识、缺乏合适的动物模型来测试疫苗的疗效、以及缺乏用于疫苗输送平台的知识。我们的分析支持使用多种抗原，包括参与病毒进入的五个主要糖蛋白中的两种或更多种（gp350、gB、gH/gL、gp42），以及一种多聚体方法来呈现这些抗原。我们预计，应用两种使用不足的挑战模型，即易受恒河猴淋巴组织细胞病毒（一种 EBV 同源病毒）感染的恒河猴和普通狨猴，将允许建立免疫保护的相关因素，并获得更具普遍性的数据。
系统审查注册
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=198440，标识符 PROSPERO I.D. CRD4202019844.
Zotero 插件