Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina.
Institute for Immunity and Transplantation, University College London, London, United Kingdom.
J Infect Dis. 2020 Mar 5;221(Suppl 1):S45-S59. doi: 10.1093/infdis/jiz428.
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.
人巨细胞病毒（HCMV）是导致婴儿先天缺陷的最常见感染原因，也是实体器官和造血干细胞移植受者发病率和死亡率显著增加的病因。人们迫切希望开发疫苗或免疫疗法来降低 HCMV 相关疾病的负担，但在该领域近半个世纪的研究和开发之后，我们仍然缺乏这种干预措施。确定保护性免疫相关因素是一个能够实现有针对性的疫苗/免疫疗法发现和对临床性能进行知情评估的过程。此前，HCMV 领域的研究结果是根据各种临床终点来衡量的，包括病毒获得、全身复制和疾病进展。本文依次回顾了针对这些终点的保护性免疫相关因素，表明控制 HCMV 可能取决于先天免疫因素、抗体和 T 细胞反应的组合。此外，保护性免疫反应具有异质性，没有单一的免疫参数可以预测对所有临床结果和 HCMV 感染阶段的保护。对特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，并指导预防 HCMV 介导的先天性和移植疾病的疫苗或免疫疗法的临床前和临床评估。
