Year: 2026
Type: preprint
Abstract: SUMMARY Humoral immune mechanisms that can contribute to limiting HCMV disease include neutralizing antibodies that block viral entry and Fc-mediated effector functions that promote elimination of infected cells. Here, we identify the gH/UL116 envelope complex as a naturally immunogenic target that elicits antibodies capable of mediating both of these immune mechanisms. Using single-cell sorting of antigen-specific memory B cells, we isolated gH/UL116-reactive monoclonal antibodies from HCMV-seropositive donors. Epitope mapping showed that gH binding was required for virus neutralization, whereas UL116 targeting was associated with potent and broad Fcγ receptor (FcγR) activation. Furthermore, cryo-electron microscopy provided high-resolution structures revealing how UL116-specific antibodies bind gH/UL116. In mice, gH/UL116 immunization elicited serum IgG responses whose binding titers strongly correlated with both neutralization and mouse FcγR activation. Together, these findings provide an epitope-level map linking antibody specificity to neutralization and FcγR activation across HCMV gH-associated complexes and position gH/UL116 as a promising HCMV vaccine candidate.
Authors: Artem Ashurov, Katja Hoffmann, Ajit R. Ramamohan, Krithika P. Karthigeyan, Anna Ashurov, Markus Rotzler, Ann-Kathrin Kohl, Gretel M. Torres, Christian Binuya, Caitlin Williams, Chelsea M. Crooks, Linda Schlachter, Danylo Shestopal, Leon Ullrich, Chiara Hornung, Ramin Lotfi, Philipp Kolb, Christoph Kreer, Manuel Koch, Sallie R. Permar, Hartmut Hengel, Jason S. McLellan, Florian Klein, Matthias Zehner
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7222893981