Early insights into viability of Ebola monoclonal antibodies for the 2026 Bundibugyo virus disease outbreak
Domaine:
healthcareType de record:
paper
Créateur:
DauKevGraSyr
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Spr
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Abstract
The 2026 Bundibugyo virus disease (BVD) outbreak in the DRC and Uganda raises urgent questions about the efficacy of existing Ebola virus (EBOV) monoclonal antibodies (mAbs) against Bundibugyo virus (BDBV). Here, we perform genomic and structural analyses of 44 BDBV sequences, including 12 from the 2026 outbreak, to assess mAb binding to the viral glycoprotein (GP). While the MBP134 cocktail epitopes remain conserved, mAb114 (Ebanga) binding is compromised by E112D and P116A mutations, causing off-target binding and reduced affinity. Structural modeling of Inmazeb shows that while Odesivimab maintains epitope binding, Atoltivimab and Maftivimab fail to bind their designated sites individually, though the complete trimeric cocktail demonstrates BDBV synergistic binding. These findings suggest that mAb114 could have reduced efficacy against BDBV due to epitope mutations affecting binding affinity, whereas MBP134 retains conserved targeting and holds promise as a broadly protective therapeutic. The complex binding behavior of Inmazeb components points to the importance of antibody combinatorial effects for treatment efficacy and warrants urgent experimental validation through neutralization assays.
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