Farrell, M. K. | Search bioRxiv

bioRxiv2026

HCMV glycoprotein B, but not the pentameric complex, is a key target of antibody-mediated phagocytosis

Human cytomegalovirus (HCMV) is a leading infectious cause of birth defects globally with devastating fetal health outcomes, and there is currently no HCMV vaccine available. Glycoprotein B (gB) and the pentameric complex (PC) are immunodominant HCMV envelope proteins and candidates of interest in vaccine development due to their ability to elicit strong anti-HCMV neutralization responses. Recent evidence implicates non-neutralizing antibody functions in protection from vertical HCMV transmission, but the involvement of gB and PC in these responses remains incompletely understood. We evaluated immune responses against HCMV elicited by a gB protein subunit vaccine with and without PC in a preclinical rabbit study. Despite improved neutralization and inhibition of cell-associated viral spread, the inclusion of PC did not enhance antibody-mediated phagocytosis or Fc{gamma}R activation against HCMV virions or infected cells compared to gB alone. We additionally found a reduction in phagocytosis function by an HCMV hyperimmune globulin when blocked against gB, but not PC, suggesting that gB is a target of phagocytosis-mediating antibodies while PC is not. Given that antibody-mediated phagocytosis but not neutralization has been associated with protection from vertical HCMV transmission, these findings support the continued assessment of gB, but not PC, as a vaccine antigen for the prevention of vertical transmission via non-neutralizing antibodies to reduce the congenital HCMV burden worldwide.

immunology↗

bioRxiv2025

Sialidases derived from Gardnerella vaginalis remodel the sperm glycocalyx and impair sperm function

Bacterial vaginosis (BV), a dysbiosis of the vaginal microbiome, affects approximately 30 percent of women worldwide (up to 50% in some regions) and is associated with several adverse health outcomes including preterm birth and increased incidence of sexually transmitted infections (STIs). BV-associated bacteria such as Gardnerella vaginalis and Prevotella timonensis damage the vaginal mucosa through the activity of sialidase enzymes that remodel the epithelial glycocalyx and degrade mucin glycoproteins. This damage may contribute to adverse health outcomes. However, whether BV-associated glycolytic enzymes also damage sperm has not yet been determined. Here, we show that sialidase-mediated glycocalyx remodeling of human sperm increases sperm susceptibility to damage and adversely affects their function in vitro. Specifically, we report that sperm motility was not adversely affected by sialidase treatment, but desialylated human sperm demonstrate increased susceptibility to agglutination and complement-mediated cytotoxicity as well as impaired transit through cervical mucus. Our results demonstrate mechanisms by which BV-associated sialidases affect sperm survival and function and potentially contribute to adverse reproductive outcomes such as infertility.

immunology↗