Perotti Michela, Perez Laurent
Faculty of Biomedical Sciences, Institute for Research in Biomedicine, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland.
Institute of Microbiology, ETH Zürich, 8093 Zürich, Switzerland.
Viruses. 2019 Dec 28;12(1):35. doi: 10.3390/v12010035.
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.
人类巨细胞病毒（HCMV）感染了全球70%以上的人口。HCMV是免疫功能低下患者高发病率和高死亡率的原因，并且仍然是先天性出生缺陷的主要病毒病因。尽管在疫苗和治疗方法研发方面付出了巨大努力，但HCMV感染在免疫功能低下个体和新生儿中仍然是尚未满足的临床需求以及一种危及生命的疾病。对HCMV血清阳性患者的免疫组库进行分析，使得人们能够识别出几种用于疫苗设计的潜在抗原。然而，近期的HCMV疫苗临床试验在疗效方面并未取得令人满意的结果。因此，将抗原与正交技术相结合以进一步增强中和抗体的诱导，可能会提高疫苗在人体中达到保护效力的可能性。事实上，已知以重复阵列形式呈现多个抗原拷贝比其可溶性对应物能引发更强有力的体液免疫反应。病毒样颗粒（VLP）和纳米颗粒（NP）是用于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，在其表面呈递复杂的糖蛋白抗原。在本综述中，我们描述了对HCMV免疫反应的一些关键方面，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。
