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Immune Correlates of Protection Against Human Cytomegalovirus Acquisition, Replication, and Disease
The Journal of Infectious Diseases ( IF 6.4 ) Pub Date : 2020-03-05 , DOI: 10.1093/infdis/jiz428
Cody S Nelson 1 , Ilona Baraniak 2 , Daniele Lilleri 3 , Matthew B Reeves 2 , Paul D Griffiths 2 , Sallie R Permar 1
Affiliation  

Human cytomegalovirus (HCMV) is the most common infectious cause of infant birth defects and an etiology of significant morbidity and mortality in solid organ and hematopoietic stem cell transplant recipients. There is tremendous interest in developing a vaccine or immunotherapeutic to reduce the burden of HCMV-associated disease, yet after nearly a half-century of research and development in this field we remain without such an intervention. Defining immune correlates of protection is a process that enables targeted vaccine/immunotherapeutic discovery and informed evaluation of clinical performance. Outcomes in the HCMV field have previously been measured against a variety of clinical end points, including virus acquisition, systemic replication, and progression to disease. Herein we review immune correlates of protection against each of these end points in turn, showing that control of HCMV likely depends on a combination of innate immune factors, antibodies, and T-cell responses. Furthermore, protective immune responses are heterogeneous, with no single immune parameter predicting protection against all clinical outcomes and stages of HCMV infection. A detailed understanding of protective immune responses for a given clinical end point will inform immunogen selection and guide preclinical and clinical evaluation of vaccines or immunotherapeutics to prevent HCMV-mediated congenital and transplant disease.

中文翻译:

防止人类巨细胞病毒获得、复制和疾病的免疫相关性

人巨细胞病毒 (HCMV) 是婴儿出生缺陷最常见的感染原因,也是实体器官和造血干细胞移植受者显着发病率和死亡率的病因。人们对开发疫苗或免疫疗法以减轻 HCMV 相关疾病的负担有着极大的兴趣,但在该领域近半个世纪的研究和开发之后,我们仍然没有这样的干预措施。定义保护的免疫相关性是一个过程,可以实现有针对性的疫苗/免疫治疗发现和临床表现的知情评估。HCMV 领域的结果之前已经根据各种临床终点进行了测量,包括病毒获取、系统复制和疾病进展。在此,我们依次回顾了针对每个终点的保护的免疫相关性,表明对 HCMV 的控制可能取决于先天免疫因子、抗体和 T 细胞反应的组合。此外,保护性免疫反应是异质的,没有单一的免疫参数可以预测针对 HCMV 感染的所有临床结果和阶段的保护。对给定临床终点的保护性免疫反应的详细了解将为免疫原选择提供信息,并指导疫苗或免疫疗法的临床前和临床评估,以预防 HCMV 介导的先天性和移植性疾病。没有单一的免疫参数可以预测针对 HCMV 感染的所有临床结果和阶段的保护作用。对给定临床终点的保护性免疫反应的详细了解将为免疫原选择提供信息,并指导疫苗或免疫疗法的临床前和临床评估,以预防 HCMV 介导的先天性和移植性疾病。没有单一的免疫参数可以预测针对 HCMV 感染的所有临床结果和阶段的保护作用。对给定临床终点的保护性免疫反应的详细了解将为免疫原选择提供信息,并指导疫苗或免疫疗法的临床前和临床评估,以预防 HCMV 介导的先天性和移植性疾病。
更新日期:2020-03-05
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