Summary
A bioRxiv preprint reports that antibodies targeting the HCMV gH/UL116 envelope complex can neutralize the virus or activate Fcγ receptors, depending on where they bind. Immunization with the complex also elicited antibody responses in mice linked to both activities.
Researchers report that antibodies against the human cytomegalovirus (HCMV) gH/UL116 envelope complex can have two different immune activities: blocking viral entry or activating Fcγ receptors. The findings, published as a bioRxiv preprint posted on October 17, 2026, connect antibody binding sites with these distinct functions and identify gH/UL116 as a potential vaccine target.
HCMV is a virus, and antibodies can contribute to immune defence in more than one way. Neutralizing antibodies interfere with viral entry into cells. Other antibody functions rely on the antibody’s Fc region binding Fcγ receptors on immune cells, which can promote responses against infected cells.
Different binding sites, different antibody activities
The researchers isolated monoclonal antibodies—individual antibodies with a single binding specificity—from antigen-specific memory B cells of HCMV-seropositive donors. They used single-cell sorting to obtain the cells and mapped where the antibodies bound on the gH/UL116 complex.
The preprint reports that binding to gH was required for virus neutralization. Antibodies targeting UL116, by contrast, were associated with potent and broad Fcγ receptor activation. The distinction suggests that the part of the complex an antibody recognizes can shape which immune function it performs.
The team also used cryo-electron microscopy to determine high-resolution structures of UL116-specific antibodies bound to the gH/UL116 complex. These structures show how the antibodies engage their target and add a structural view to the functional mapping.
Mouse immunization links antibody responses to both activities
In mice immunized with gH/UL116, the researchers observed serum IgG responses. The amount of antibody binding to the complex strongly correlated with both virus neutralization and mouse Fcγ receptor activation.
The results bring together antibody isolation from human donors, structural analysis and an immunization experiment in mice. They support the researchers’ proposal that gH/UL116 could be developed as an HCMV vaccine candidate, with the potential to elicit antibodies that act through more than one immune mechanism.
This is preclinical research reported in a preprint. The mouse experiment measured antibody responses and functional activities; the abstract does not report a human vaccine study or a protection outcome. Whether the findings translate into protection in people remains a key step for evaluating the candidate.