B cell response to HCMV gH/UL116 elicits neutralizing and FcγR-activating antibodies

Abstract

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 Fc{gamma} receptor (Fc{gamma}R) 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 Fc{gamma}R activation. Together, these findings provide an epitope-level map linking antibody specificity to neutralization and Fc{gamma}R activation across HCMV gH-associated complexes and position gH/UL116 as a promising HCMV vaccine candidate.

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BibTeX

@misc{ashurov2026cell,
  title = {{B cell response to HCMV gH/UL116 elicits neutralizing and FcγR-activating antibodies}},
  author = {A. Ashurov and K. Hoffmann and A. R. Ramamohan and K. P. Karthigeyan and A. Ashurov and M. Rotzler and A.-K. Kohl and G. M. Torres and C. Binuya and C. Williams and C. M. Crooks and L. Schlachter and D. Shestopal and L. Ullrich and C. Hornung and R. Lotfi and P. Kolb and C. Kreer and M. Koch and S. R. Permar and H. Hengel and J. S. McLellan and F. Klein and M. Zehner},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.11.758335},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.11.758335v1},
  note = {CC BY},
}

RIS

TY  - UNPB
TI  - B cell response to HCMV gH/UL116 elicits neutralizing and FcγR-activating antibodies
AU  - A. Ashurov
AU  - K. Hoffmann
AU  - A. R. Ramamohan
AU  - K. P. Karthigeyan
AU  - A. Ashurov
AU  - M. Rotzler
AU  - A.-K. Kohl
AU  - G. M. Torres
AU  - C. Binuya
AU  - C. Williams
AU  - C. M. Crooks
AU  - L. Schlachter
AU  - D. Shestopal
AU  - L. Ullrich
AU  - C. Hornung
AU  - R. Lotfi
AU  - P. Kolb
AU  - C. Kreer
AU  - M. Koch
AU  - S. R. Permar
AU  - H. Hengel
AU  - J. S. McLellan
AU  - F. Klein
AU  - M. Zehner
PY  - 2026
DA  - 2026/10/11
PB  - bioRxiv
DO  - 10.64898/2026.10.11.758335
UR  - https://www.biorxiv.org/content/10.64898/2026.10.11.758335v1
AB  - 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 Fc{gamma} receptor (Fc{gamma}R) 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 Fc{gamma}R activation. Together, these findings provide an epitope-level map linking antibody specificity to neutralization and Fc{gamma}R activation across HCMV gH-associated complexes and position gH/UL116 as a promising HCMV vaccine candidate.
ER  -

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