Correlates of human Cytomegalovirus Cervical Shedding in Seropositive Women: Implications for Vaccine Development.

Abstract

Congenital human cytomegalovirus (HCMV) infection, caused by maternal transmission, is a leading cause of congenital disabilities and poses a substantial global disease burden. Historically, HCMV vaccine development has centered on protecting seronegative women. However, accumulating evidence indicates that the majority of HCMV infections in newborns stem from non-primary infections (reinfection or reactivation). Although HCMV shedding may have diagnostic value, the relationship between viral shedding and host immune status in seropositive individuals remains poorly elucidated. A total of 142 HCMV-seropositive women of reproductive age were enrolled from the Reproductive Medicine Clinic of Taizhou People's Hospital, Jiangsu Province, China. Serum samples and cervical secretions were collected, and antibody levels and HCMV DNA loads were detected, respectively. Serum IgG binding to postfusion glycoprotein B (gB), cell-surface-expressed gB, and pentameric complex (PC) was significantly associated with HCMV shedding in cervical secretions. In contrast, no significant associations were observed between cervical shedding and Serum IgG binding to prefusion gB or the structural antigen pp150, nor with neutralizing antibody (NAb) titers against Towne and ADR131 strains in MRC-5 cells or ADR131 strain in ARPE-19 cells. These findings advance the current understanding of the interplay between viral shedding and humoral immunity in HCMV-seropositive individuals. Importantly, they provide novel evidence supporting site-specific HCMV shedding as a potential biomarker for reinfection/reactivation, and a potential exploratory surrogate marker for subsequent vaccine endpoint validation. This study thus offers new insights for the development of HCMV vaccines targeting seropositive populations.