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. 2020 Mar 5;221(Suppl 1):S128-S134.
doi: 10.1093/infdis/jiz537.

Choice of Study Populations for Vaccines

Paul Griffiths  1 , Brenna Hughes  2
Affiliations

Choice of Study Populations for Vaccines

Paul Griffiths et al. J Infect Dis. .

Abstract

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.

Keywords: ante-natal; cytomegalovirus; immune responses; transplant; vaccination.

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Figures

Figure 1.
Figure 1.
Common sources of cytomegalovirus (CMV) for seronegative women and implications for sample collection and clinical trial design. By analogy with transplant patients at risk of CMV infection, family members are considered as donors of virus for the female recipient. Gray represents uninfected and red represents infected. Collection and storage of serial samples from all family members is envisaged as part of clinical trial design. This would allow the strain of CMV causing congenital infection to be formally linked with the strain in the donor.
Figure 2.
Figure 2.
Common sources of cytomegalovirus (CMV) for seropositive women and implications for sample collection and clinical trial design. By analogy with transplant patients at risk of CMV infection, family members are considered as donors of virus for the female recipient. Gray represents uninfected and red represents infected. Collection and storage of serial samples from all family members is envisaged as part of clinical trial design. This would allow the strain of CMV causing congenital infection to be formally linked with the strain in the donor. Comparison with the infection rate among people receiving placebo would prove that a vaccine could protect against either reactivation of maternal infection or reinfection from a defined donor or both.
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