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bioRxiv · 10.64898/2026.01.03.697490

Sub-neutralizing concentrations of Zika virus IgM monoclonal antibodies reduce IgG-mediated antibody-dependent enhancement of infectivity.

Lingemann, M.·McGee, T. J.·Sidoti Migliore, G.·DeLuca, J. M.·Whitehead, S. S.·Bonsignori, M.
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Abstract

Zika virus (ZIKV) is an arthropod-borne flavivirus endemic to Latin America and Africa for which IgG-mediated antibody-dependent enhancement of infectivity (ADE) is a phenomenon of concern. The interplay 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 against the whole panel, 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.

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Lingemann, M., McGee, T. J., Sidoti Migliore, G., DeLuca, J. M., Whitehead, S. S., Bonsignori, M.. 2026-01-03. Sub-neutralizing concentrations of Zika virus IgM monoclonal antibodies reduce IgG-mediated antibody-dependent enhancement of infectivity.. https://doi.org/10.64898/2026.01.03.697490

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