Maple Peter A, Ascherio Alberto, Cohen Jeffrey I, Cutter Gary, Giovannoni Gavin, Shannon-Lowe Claire, Tanasescu Radu, Gran Bruno
Division of Clinical Neuroscience, Section of Clinical Neurology, University of Nottingham, Nottingham, United Kingdom.
Department of Neurology, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom.
Front Neurol. 2022 Jun 24;13:887794. doi: 10.3389/fneur.2022.887794. eCollection 2022.
There is increasing evidence suggesting that Epstein-Barr virus infection is a causative factor of multiple sclerosis (MS). Epstein-Barr virus (EBV) is a human herpesvirus, Human Gammaherpesvirus 4. EBV infection shows two peaks: firstly, during early childhood and, secondly during the teenage years. Approximately, 90-95% of adults have been infected with EBV and for many this will have been a subclinical event. EBV infection can be associated with significant morbidity and mortality; for example, primary infection in older children or adults is the leading cause of infectious mononucleosis (IM). A disrupted immune response either iatrogenically induced or through genetic defects can result in lymphoproliferative disease. Finally, EBV is oncogenic and is associated with several malignancies. For these reasons, vaccination to prevent the damaging aspects of EBV infection is an attractive intervention. No EBV vaccines have been licensed and the prophylactic vaccine furthest along in clinical trials contains the major virus glycoprotein gp350. In a phase 2 study, the vaccine reduced the rate of IM by 78% but did not prevent EBV infection. An EBV vaccine to prevent IM in adolescence or young adulthood is the most likely population-based vaccine strategy to be tested and adopted. National registry studies will need to be done to track the incidence of MS in EBV-vaccinated and unvaccinated people to see an effect of the vaccine on MS. Assessment of vaccine efficacy with MS being a delayed consequence of EBV infection with the average age of onset being approximately 30 years of age represents multiple challenges.
越来越多的证据表明,爱泼斯坦-巴尔病毒感染是多发性硬化症(MS)的致病因素。爱泼斯坦-巴尔病毒(EBV)是一种人类疱疹病毒,即人类γ疱疹病毒4型。EBV感染呈现两个高峰:首先是在幼儿期,其次是在青少年时期。大约90%-95%的成年人曾感染过EBV,而且对许多人来说,这可能是一次亚临床感染事件。EBV感染可能与显著的发病率和死亡率相关;例如,大龄儿童或成年人的初次感染是传染性单核细胞增多症(IM)的主要病因。医源性诱导或遗传缺陷导致的免疫反应紊乱可引发淋巴增殖性疾病。最后,EBV具有致癌性,与多种恶性肿瘤相关。出于这些原因,通过接种疫苗来预防EBV感染的有害影响是一种有吸引力的干预措施。目前尚无已获许可的EBV疫苗,临床试验中进展最远的预防性疫苗含有主要病毒糖蛋白gp350。在一项2期研究中,该疫苗使IM的发病率降低了78%,但并未预防EBV感染。预防青少年或青年期IM的EBV疫苗是最有可能进行测试和采用的基于人群的疫苗策略。需要开展国家登记研究来追踪接种和未接种EBV疫苗人群中的MS发病率,以观察该疫苗对MS的影响。鉴于MS是EBV感染的延迟后果,平均发病年龄约为30岁,评估疫苗效力面临多重挑战。