Early insights into predicted efficacy of Ebola monoclonal antibodies for the 2026 Bundibugyo virus disease outbreak
Year: 2026
Type: article
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 computational models predict mAb114 efficacy against BDBV may be compromised 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. These observations warrant urgent experimental validation through neutralization assays. Rapid predictive methods narrow the solution space in an outbreak setting. In this computational study, the authors find that cocktail treatments for Ebola Zaire could be more effective than monotherapies against the 2026 Bundibugyo strain.
Source: Nature Communications
Authors: Kevin Cissy Nabukeera, Gradi Luakanda-Ndelemo, Syrus Semawule, Alisen Ayitewala, Pascal Adroba-Tandele, Andrew Walakira, Adrienne Amuri-Aziza, Daan Jansen, Ronald Galiwango, Eddy Kinganda-Lusamaki, Andrew Tebba, Christian Ngandu, Aloysious Ssemaganda, Olivier Tshiani-Mbaya, Stephen Kanyerezi, Judith Kyokushaba, Prince Akil-Bandali, Carol Makoha, Hellen Rosette Oundo, Servet Kimbonza, Stephen Balinandi, Daniel Mukadi-Bamuleka, Valeria Nakintu, Justus Nsio, Ibrahimm Mugerwa, Daniel Kadobera, Daniel Euriene, Sabue Mulangu, Ahidjo Ayouba, Micheal Eliu, Sam Gidudu, Henry Kyobe Bosa, Misaki Wayengera, Anne W. Rimoin, Benard Lubwama, Atek Kagirita, Steve Ahuka-Mundeke, Dieudonné Mwamba, Andrew Kambugu, Pontiano Kaleebu, Christian Happi, Laurens Liesenborghs, Miles W. Carroll, Piet Maes, Jean B. Nachega, Martine Peeters, Pierre Akilimali, Ronnie Bahatungire, Allan Muruta, Jason Kindrachuk, Andrew Rambaut, Daniel Kyabayinze, Charles Olaro, Koen Vercauteren, Jean-Jacques Muyembe-Tamfum, Susan Nabadda, Diana Atwine, Daudi Jjingo, Tony Wawina-Bokalanga, Placide Mbala-Kingebeni, Isaac Ssewanyana
Institutions: Makerere University, National Institute of Biomedical Research, Ministry of Health, National Health Laboratory and Diagnostics Services, Infectious Diseases Institute, KU Leuven, Instituut voor Tropische Geneeskunde, Inserm, Université de Montpellier, University of Kinshasa, Recherches Translationnelles sur le VIH et les Maladies Infectieuses, Cliniques Universitaires de Kinshasa, Ministry of Public Health, Uganda Virus Research Institute, Africa Centres for Disease Control and Prevention, University of California, Los Angeles, Redeemer's University, Centre for Human Genetics, University of Oxford, Université Libre de Bruxelles, University of Pittsburgh, Ecole de santé publique de Kinshasa, University of Manitoba, University of Edinburgh, University of the Western Cape
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W7214455207
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