ETIDIOH - NEW

ABSTRACT A cocktail of human monoclonal antibodies 1C3 and 1C11 previously protected macaques from a lethal exposure to either Ebola virus (EBOV) or Sudan virus (SUDV). 1C3 is of particular interest because its paratope strongly binds with unique stoichiometry to the glycoprotein head of several orthoebolaviruses , resulting in neutralization of EBOV and SUDV . Therefore, we evaluated the protective activity of 1C3 as a standalone therapeutic in macaques exposed to either EBOV or SUDV. Two doses of 1C3 monotherapy, administered 4 and 7 days post-exposure, did not protect SUDV-exposed macaques and partially protected EBOV-exposed macaques . Notably, in a macaque that succumbed to EBOV infection, we identified two mutually exclusive escape mutations that emerged immediately after the first dose and resulted in two amino acid changes at the 1C3 binding site . We also detected a subconsensus treatment-emergent mutation likely affecting the 1C3 binding site in all three deceased SUDV-expose...

Abstract Background .  Sudan virus (SUDV) has caused multiple outbreaks in Uganda over the past two decades, leading to significant morbidity and mortality . The recent outbreaks in 2022 and 2025 highlight the ongoing threat posed by SUDV and the challenges in its containment. This study aims to characterize the epidemiological patterns and phylogenomic evolution of SUDV outbreaks in Uganda, identifying key factors influencing transmission and disease severity.  Methods .  We conducted a retrospective observational study analyzing epidemiological and genomic data from SUDV outbreaks in Uganda between 2000 and 2025. Epidemiological data were collected from official sources, including the Ugandan Ministry of Health and the World Health Organization, supplemented with reports from public health organizations. Genomic sequences of SUDV were analyzed to investigate viral evolution and identify genetic variations associated with pathogenicity and transmissibility.  Results...

Abstract In 2018, a clinical trial of four investigational therapies for Ebola virus disease (EVD), known as the PALM trial , was conducted in the Democratic Republic of Congo . All patients received either the antiviral remdesivir (RDV) or a monoclonal antibody product : ZMapp, mAb114 (Ebanga), or REGN-EB3 (Inmazeb). The study concluded that both mAb114 and REGN-EB3 were superior to ZMapp and RDV in reducing mortality from EVD. However, the data suggested that some patients in the RDV and ZMapp groups might have been sicker at the time of treatment initiation. Here, we assessed the efficacy of each of these therapies in a uniformly lethal rhesus monkey model of EVD when treatment was initiated 5 days after Ebola exposure. Treatment with RDV, mAb114, REGN-EB3, and ZMapp each resulted in similar survival (approximately 40% ). Survival was associated with circulating viral load at treatment initiation. A trend of more escape mutants in the GP1 and GP2 domains was observed for the mAb114 ...

Abstract Ebola virus (EBOV) and Marburg virus (MARV) are zoonotic filoviruses that cause hemorrhagic fever in humans . Correlative data implicate bats as natural EBOV hosts , but neither a full-length genome nor an EBOV isolate has been found in any bats sampled. Here, we model filovirus infection in the Jamaican fruit bat (JFB), Artibeus jamaicensis, by inoculation with either EBOV or MARV through a combination of oral, intranasal, and subcutaneous routes . Infection with EBOV results in systemic virus replication and oral shedding of infectious virus. MARV replication is transient and does not shed. In vitro, JFB cells replicate EBOV more efficiently than MARV, and MARV infection induces innate antiviral responses that EBOV efficiently suppresses. Experiments using VSV pseudoparticles or replicating VSV expressing the EBOV or MARV glycoprotein demonstrate an advantage for EBOV entry and replication early , respectively, in JFB cells. Overall, this study describes filovirus species-sp...

{Excerpt} In a global first, Uganda’s Ministry of Health, the World Health Organization (WHO) and other partners today launched a first ever vaccine trial for Ebola from the Sudan species of the virus, and at an unprecedented speed for a randomized vaccine trial in an emergency . The principal investigators from Makerere University and the Uganda Virus Research Institute (UVRI), with support from WHO and other partners, have worked tirelessly to get the trial ready in 4 days since the outbreak was confirmed on 30 January. It is the first trial to assess the clinical efficacy of a vaccine against Ebola disease due to Sudan virus . The speed was achieved through advanced research preparedness, while ensuring full compliance with national and international regulatory and ethical requirements. The candidate vaccine was donated by IAVI , with financial support from WHO, the Coalition for Epidemic Preparedness Innovations (CEPI), Canada’s International Development Research Centre (IDRC), and...