IgM monoclonal antibodies reduce IgG-mediated antibody-dependent enhancement of Zika and dengue virus infectivity
Abstract
Zika virus (ZIKV) is an arthropod-borne flavivirus endemic to Latin America, Africa, and Southeast Asia for which IgG-mediated antibody-dependent enhancement of infectivity (ADE) is a phenomenon of concern. The dynamics between flavivirus-specific antibodies of the IgG and IgM isotypes are mostly unknown. Here, we used DH1017.IgM, a previously described human-derived, pentameric, ultrapotent neutralizing ZIKV IgM monoclonal antibody (mAb) and a recombinantly produced IgM version of neutralizing EDE1 mAb C8 (C8.IgM) to assess if IgM antibodies can interfere with IgG-mediated ADE in vitro. Both mAbs consistently reduced IgG-mediated ADE across a panel of ZIKV-binding IgG mAbs in a dose-dependent manner. ADE mitigation was achieved at DH1017.IgM sub-neutralizing concentrations. C8.IgM also mitigated IgG-mediated ADE for ZIKV and dengue virus (DENV), demonstrating generalizability. Finally, DH1017.IgM confirmed inhibition of ADE at sub-neutralizing concentrations in sera of ZIKV-infected individuals. In conclusion, mAbs of the IgM isotype may potently counter the adverse effects of IgG-mediated ADE.
Related
- Phenuivirus glycoprotein Gc domain is a conserved target of cross-functional monoclonal antibodies
- N1 neuraminidase monoclonal antibodies 2H08 and 3H03 have decreased binding and inhibition properties against H1N1 influenza viruses circulating after 2018
- A Panel of Human Monoclonal Antibodies for Tracking the Antigenic Evolution of Influenza H5N1 Clade 2.3.4.4b
- Structural analysis of the specificity of three neutralising human monoclonal antibodies against poliovirus
- DNA-Barcoded Polysaccharide Specific Monoclonal Antibodies Facilitate Sensitive and Multiplexed Detection of Cell Wall Polymers.
BibTeX
@article{lingemann2026monoclonal,
title = {{IgM monoclonal antibodies reduce IgG-mediated antibody-dependent enhancement of Zika and dengue virus infectivity}},
author = {Matthias Lingemann and Taylor J. McGee and Giacomo Sidoti Migliore and Jenna M. DeLuca and Stephen S. Whitehead and Mattia Bonsignori},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.117897},
url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03280-3},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - IgM monoclonal antibodies reduce IgG-mediated antibody-dependent enhancement of Zika and dengue virus infectivity
AU - Matthias Lingemann
AU - Taylor J. McGee
AU - Giacomo Sidoti Migliore
AU - Jenna M. DeLuca
AU - Stephen S. Whitehead
AU - Mattia Bonsignori
PY - 2026
DA - 2026/10/19
JO - iScience
DO - 10.1016/j.isci.2026.117897
UR - https://www.cell.com/iscience/fulltext/S2589-0042(26)03280-3
AB - Zika virus (ZIKV) is an arthropod-borne flavivirus endemic to Latin America, Africa, and Southeast Asia for which IgG-mediated antibody-dependent enhancement of infectivity (ADE) is a phenomenon of concern. The dynamics between flavivirus-specific antibodies of the IgG and IgM isotypes are mostly unknown. Here, we used DH1017.IgM, a previously described human-derived, pentameric, ultrapotent neutralizing ZIKV IgM monoclonal antibody (mAb) and a recombinantly produced IgM version of neutralizing EDE1 mAb C8 (C8.IgM) to assess if IgM antibodies can interfere with IgG-mediated ADE in vitro. Both mAbs consistently reduced IgG-mediated ADE across a panel of ZIKV-binding IgG mAbs in a dose-dependent manner. ADE mitigation was achieved at DH1017.IgM sub-neutralizing concentrations. C8.IgM also mitigated IgG-mediated ADE for ZIKV and dengue virus (DENV), demonstrating generalizability. Finally, DH1017.IgM confirmed inhibition of ADE at sub-neutralizing concentrations in sera of ZIKV-infected individuals. In conclusion, mAbs of the IgM isotype may potently counter the adverse effects of IgG-mediated ADE.
SN - 2589-0042
ER -