Choice of Study Populations for Vaccines.

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.