Institute for Immunity and Transplantation, UCL, London, United Kingdom.
Department of Obstetrics and Gynecology, Duke University, Durham, North Carolina, USA.
J Infect Dis. 2020 Mar 5;221(Suppl 1):S128-S134. doi: 10.1093/infdis/jiz537.
The natural history of cytomegalovirus (CMV) infection is complex. Individuals may experience primary infection, reactivation of latent infection, or reinfection with a new strain despite natural immunity. The ability of this virus to continue to replicate despite substantial immune responses is attributable to the many immune evasion genes encoded within its genome. Given this complex natural history and immunology, the design of clinical trials of CMV vaccines may require components not usually found in trials of vaccines designed to protect against viruses that cause only acute infections. In this article, we focus on specific aspects of clinical trial design that could be adopted to address the complexities of CMV infections. We consider women of childbearing age, toddlers, recipients of solid organ transplantation, and stem cell transplant patients, emphasizing the parallels between women and solid organ transplantation that could allow vaccines to be developed in parallel in both these patient groups. We emphasize the potential for studies of passive immunity to inform the selection of immunogens as candidates for active immunization and vice versa. We also illustrate how application of whole-genomic sequencing could document whether vaccines protect against reactivation or reinfection of CMV or both.
巨细胞病毒（CMV）感染的自然史较为复杂。尽管存在天然免疫，个体仍可能经历原发感染、潜伏感染的再激活或新毒株的再感染。该病毒能够在大量免疫应答的情况下继续复制，这归因于其基因组中编码的许多免疫逃逸基因。鉴于这种复杂的自然史和免疫学特性，CMV 疫苗的临床试验设计可能需要采用通常在预防仅引起急性感染的病毒的疫苗临床试验中找不到的组件。本文重点介绍可用于解决 CMV 感染复杂性的临床试验设计的具体方面。我们考虑了育龄妇女、幼儿、实体器官移植受者和干细胞移植患者，强调了妇女和实体器官移植之间的相似性，这可使这两个患者群体中的疫苗能够并行开发。我们强调了被动免疫研究为选择免疫原作为主动免疫候选物以及反之提供信息的潜力。我们还说明了全基因组测序的应用如何能够记录疫苗是否能预防 CMV 的再激活或再感染，或两者兼防。
