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Virus-Like Particles and Nanoparticles for Vaccine Development against HCMV

机译:用于HCMV疫苗开发的病毒样颗粒和纳米颗粒

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摘要

Human cytomegalovirus (HCMV) infects more than 70% of the human population worldwide. HCMV is responsible for high morbidity and mortality in immunocompromised patients and remains the leading viral cause of congenital birth defects. Despite considerable efforts in vaccine and therapeutic development, HCMV infection still represents an unmet clinical need and a life-threatening disease in immunocompromised individuals and newborns. Immune repertoire interrogation of HCMV seropositive patients allowed the identification of several potential antigens for vaccine design. However, recent HCMV vaccine clinical trials did not lead to a satisfactory outcome in term of efficacy. Therefore, combining antigens with orthogonal technologies to further increase the induction of neutralizing antibodies could improve the likelihood of a vaccine to reach protective efficacy in humans. Indeed, presentation of multiple copies of an antigen in a repetitive array is known to drive a more robust humoral immune response than its soluble counterpart. Virus-like particles (VLPs) and nanoparticles (NPs) are powerful platforms for multivalent antigen presentation. Several self-assembling proteins have been successfully used as scaffolds to present complex glycoprotein antigens on their surface. In this review, we describe some key aspects of the immune response to HCMV and discuss the scaffolds that were successfully used to increase vaccine efficacy against viruses with unmet medical need.
机译:人类巨细胞病毒(HCMV)感染了全世界70%以上的人口。 HCMV导致免疫受损患者的高发病率和高死亡率,并且仍然是先天性先天缺陷的主要病毒原因。尽管在疫苗和治疗开发方面做出了巨大的努力,但HCMV感染仍然代表着未满足的临床需求和免疫受损的个人和新生儿的危及生命的疾病。 HCMV血清反应阳性患者的免疫库查询可以鉴定几种潜在的抗原用于疫苗设计。但是,最近的HCMV疫苗临床试验并未在疗效方面产生令人满意的结果。因此,将抗原与正交技术相结合以进一步增加中和抗体的诱导可以提高疫苗达到人类保护作用的可能性。实际上,已知抗原以重复阵列的多个拷贝的呈现比其可溶性对应物驱动更强健的体液免疫应答。病毒样颗粒(VLP)和纳米颗粒(NP)是多价抗原呈递的强大平台。几种自组装蛋白已成功用作支架,以在其表面上呈递复杂的糖蛋白抗原。在这篇综述中,我们描述了对HCMV免疫应答的一些关键方面,并讨论了成功用于提高针对未满足医疗需求的病毒的疫苗效力的支架。

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