The #Mengla virus (Filoviridae: #Dianlovirus)

 

Abstract

Introduction. 

Filoviruses associated with various species of pteropodid bats (Chiroptera: Pteropodidae) are traditionally regarded as potential causative agents of hemorrhagic fevers with epidemic potential. The known agents of Ebola and Marburg fevers periodically cause sporadic cases and epidemic outbreaks in African countries. Recent discoveries of novel filoviruses associated with pteropodid bats in South and Southeast Asia highlight the necessity to investigate their genetic diversity and pathogenic potential.

The aim of this study was to investigate the genetic diversity and pathogenic potential of new filoviruses associated with bats, based on literature data.

Materials and methods. 

This review is based on an analysis of published literature describing the detection and molecular characterization of novel filoviruses identified in different geographic regions, with a particular focus on filoviruses associated with pteropodid bats in South and Southeast Asia. The analyzed studies include data on virus discovery, genome organization, taxonomic classification, and experimental assessment of biological properties. 

Results. 

Several novel filoviruses have been identified by metagenomic RNA sequencing of tissues from pteropodid bats captured in South and Southeast Asia. Among them, Mengla virus was detected in tissues of pteropodid bats (Rousettus spp.) captured in Mengla County, Yunnan Province, People’s Republic of China. Owing to a high level of genetic divergence, Mengla virus was classified as a representative of a new genus, Dianlovirus, within the family Filoviridae. Although a live isolate of Mengla virus has not yet been obtained, experimental studies using chimeric minigenome systems and virus-like particles suggest that the virus may exhibit tropism for tissues of various vertebrate hosts, including humans.

Conclusion. 

Members of the family Filoviridae are widely distributed within the geographic range of their natural reservoir–pteropodid bats–across South and Southeast Asia, including viruses evolutionarily related to Ebola and Marburg viruses. Although human disease caused by Mengla virus and other recently discovered filoviruses has not been documented, the potential for cross-species transmission and the emergence of novel filovirus infections in endemic regions remains.

Source: 

Link: https://virusjour.crie.ru/jour/article/view/16805

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Confirming #ERVEBO #Vaccination to Support #Ebola Virus #Surveillance

 

Abstract

Accurate confirmation of Ebola vaccination (ERVEBO) is essential for interpreting serologic data and assessing vaccine coverage during Ebola virus (EBOV) outbreaks. Current GP1,2-based assays cannot reliably distinguish vaccine-induced immunity from responses generated by natural infection. We developed a multiplex Luminex assay incorporating EBOV GP1,2, secreted glycoprotein (sGP), and a modified vesicular stomatitis virus nucleoprotein (VSV-P-N), a vector antigen encoded by ERVEBO but absent from wild-type EBOV. By using samples from US vaccinees and controls and a small comparison set from the Democratic Republic of the Congo, we found sGP and VSV-P-N demonstrated 100% sensitivity and >97.6% specificity for identifying vaccinees. In samples collected after a ring vaccination campaign in Guinea, combined sGP and VSV-P-N positivity confirmed vaccination in 94.8% of persons with written and 90.8% of persons with verbal confirmation of vaccination history. Our findings show that sGP and VSV-P-N provide a reliable signature of ERVEBO vaccination and support improved Ebola surveillance.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/4/25-1906_article

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#Glycoprotein-specific transcriptional response contributes to differential #vaccine #protection against lethal #Ebola virus #infection

 

Abstract

Since the West African Ebola virus (EBOV) epidemic in 2014-2016, recurrent outbreaks of the EBOV-Makona variant have been driven by recrudescence and human-to-human transmission emphasizing the need for effective vaccination strategies. A live-attenuated recombinant vesicular stomatitis virus (VSV)-based vaccine expressing the EBOV-Kikwit variant glycoprotein (VSV-Kik) received FDA approval in December 2019 and provides complete, rapid protection against EBOV-Makona as early as 7 days post-vaccination (DPV). During the 2018-2020 Ebola outbreak, the VSV-Kik vaccine, known as ERVEBO, was administered to lower-risk individuals at a 5-fold dose reduction of the standard 2 × 107 PFU to provide broader population protection. Identification of a protective lower dose providing rapid protection would ease supply burdens during future outbreaks and enhance vaccine coverage. We previously generated a VSV-based vaccine expressing the glycoprotein of the Makona variant (VSV-Mak) which provided complete protection against homologous challenge 28 DPV at as low as 1 × 101 PFU. However, the transcriptional responses engendered by VSV-Mak and VSV-Kik vaccines in the context of early EBOV-Makona challenge have not yet been evaluated. In the current study, we compared transcriptional responses following a low dose (1 × 104 PFU) of lab-grade VSV-Mak or GMP-grade VSV-Kik and subsequent EBOV-Makona challenge 10 DPV. VSV-Kik provided complete protection against heterologous challenge and elicited rapid antiviral transcriptional changes followed by the activation of adaptive immunity. On the other hand, VSV-Mak only provided partial protection and induced minimal transcriptional response. These results highlight a glycoprotein-specific transcriptional response after vaccination despite the high EBOV variant homology.

Source: Vaccine, https://www.sciencedirect.com/journal/vaccine/vol/79/suppl/C

Link: https://www.sciencedirect.com/science/article/abs/pii/S0264410X26002185?via%3Dihub

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Structures of #Marburgvirus #glycoprotein and its complex with NPC1 #receptor

 

Abstract

Marburgviruses (MBVs) cause severe haemorrhagic fever with higher fatality rates than Ebola virus (EBOV). Here we show that the MBV glycoprotein (GP) mediates viral entry more efficiently than EBOV GP. Using cryo-EM, we determined structures of MBV GP in three states: (1) unbound; (2) bound to its endosomal receptor NPC1; and (3) complexed with a neutralizing nanobody. The glycan cap shields the receptor-binding site from NPC1 but only partially from the nanobody, enabling limited immune evasion. After glycan cap cleavage, NPC1 binds to MBV GP in a distinct orientation compared with EBOV GP, providing an additional anchor and enhancing receptor affinity. NPC1 engagement also induces substantial conformational changes in MBV GP, probably facilitating membrane fusion. Furthermore, MBV GP is susceptible to the neutralizing nanobody, which mimics NPC1 at the receptor-binding site. Together, our findings reveal MBV GP as a highly efficient entry mediator and suggest structural mechanisms that may contribute to its enhanced entry efficiency.

Source: Nature, https://www.nature.com/

Link: https://www.nature.com/articles/s41586-026-10240-0

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#Marburg virus disease - #Ethiopia [End of the Outbreak] (#WHO, Jan. 26 '26)

 

{Excerpt}

26 January 2026

Situation at a glance

On 26 January 2026, the Ministry of Health of Ethiopia declared the end of the Marburg virus disease (MVD) outbreak. 

This declaration came after two consecutive incubation periods (a total of 42 days) since the last person confirmed with MVD died and was given a safe and dignified burial, in accordance with WHO recommendations on 14 December 2025. 

As of 25 January 2026, a cumulative total of 19 cases, including 14 confirmed (including nine deaths) and five probable cases (all deaths), were reported. 

A total of 857 contacts listed for monitoring all had completed their 21-day follow-up as of 25 January 2026. 

WHO, through its country office and partners, provided technical, operational and financial support to the government to contain this outbreak.

Description of the situation

On 14 November 2025, after the laboratory confirmation of suspected viral hemorrhagic fever (VHF) cases in Jinka town, South Ethiopia Regional State, Ethiopia, the Ministry of Health of Ethiopia declared an outbreak of Marburg Virus Disease (MVD). 

Molecular testing conducted by the National Reference Laboratory at the Ethiopian Public Health Institute (EPHI) identified Marburg virus (MARV) in patient samples. 

This was the first time Ethiopia was reporting a MVD outbreak.

The first known case was an adult from Jinka town who developed symptoms on 23 October. 

The patient presented to the General Hospital the following day with vomiting, loss of appetite, and abdominal cramps. 

As of 25 January 2026, a cumulative total of 14 confirmed cases, including nine deaths (Case Fatality Rate (CFR) 64.3%) and five probable cases, all of whom had died, were reported by the Ministry of Health from Jinka, Malle and Dasench woredas in South Ethiopia Region and Hawassa in Sidama Region.

As of 25 January 2026, a total of 857 contacts were listed who completed 21 days of follow-up, 760 from the South Ethiopia Region and 97 from the Sidama Region. 

As of 5 January 2026, 3800 samples were tested for the virus.

On 26 January 2026, after two consecutive incubation periods (a total of 42 days), without a new confirmed case reported, after the last confirmed case died and was given a safe and dignified burial, on 14 December 2025, the Ministry of Health of Ethiopia declared the end of the MVD outbreak, as per WHO recommendations.

(...)

Source: 

Link: https://www.who.int/emergencies/disease-outbreak-news/item/2026-DON592

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An #mRNA #vaccine encoding the #Ebola virus glycoprotein induces high neutralizing #antibody titers and provides strong protection against lethal infections in mouse models

 

Abstract

Ebola virus (EBOV) is the causative agent of Ebola disease (EBOD), a viral hemorrhagic fever with a notably high case fatality rate. Current treatments for EBOD are limited to monoclonal antibodies or two licensed viral vector vaccines, a recombinant vesicular stomatitis virus (rVSV)-vectored vaccine or an adenovirus and modified vaccinia Ankara regimen. However, comparisons of protection, efficacy, and durability with alternative nucleotide platforms remain understudied. Here, we evaluated the immunogenicity of an mRNA vaccine expressing the EBOV glycoprotein (GP) in parallel with rVSV- and DNA-based vaccine platforms. The mRNA EBOV-GP vaccine, formulated in lipid nanoparticles, elicited significantly higher levels of total IgG and neutralizing antibody titers compared to the rVSV-EBOV-GP vaccine. Linear antibody epitope analysis indicated a preference for targeting the mucin-like domain in EBOV-GP1 following rVSV-based vaccination, while the mRNA platform distinctly targeted the internal fusion loop of EBOV-GP2. After characterizing the immunogenicity of the mRNA vaccine, two models of EBOD were used to demonstrate its protective efficacy: a surrogate rVSV-based challenge model of EBOD using type-I interferon deficient C57BL/6 mice and infection of BALB/c mice with authentic mouse-adapted EBOV. In both studies, the EBOV mRNA vaccine fully protected the mouse cohorts against morbidity and mortality. Additionally, the EBOV mRNA vaccine produced greater neutralizing antibody titers compared to the DNA EBOV-GP vaccine. These results suggest that an mRNA vaccine expressing EBOV-GP can induce robust, functional humoral responses that are protective against EBOD, warranting further development as an alternative to, or as part of a vaccine strategy including, viral vectored vaccines.

Source: Frontiers in Immunology, https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1682418/full

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#Genomic Insights into #Marburg Virus Strains from 2023 and 2025 #Outbreaks in Kagera, #Tanzania

 

Abstract

Marburg virus (MARV) is the primary cause of Marburg virus disease (MVD), a severe hemorrhagic fever with a high case-fatality rate. The first reported MVD outbreak in Tanzania occurred in 2023, followed by a second outbreak in 2025, both within the Kagera region. During those MVD outbreaks, 174 suspected cases were identified; of those, 10 were laboratory confirmed. After complete genome assembly and bioinformatic analyses, we found the MARV strains of the 2023 and 2025 outbreaks to be closely related and clustered with MARV strains that caused outbreaks in Rwanda (2024) and Uganda (2014). The sequences from both MVD outbreaks in Tanzania showed >99.71% nucleotide identity, suggesting a possible single spillover event followed by limited human-to-human virus transmission. Further ecologic studies are essential to identify potential spillover events, but our findings indicate that closely related MARV strains circulate in Kagera, Tanzania, posing a risk for future outbreak recurrence.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/1/25-1314_article

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Assessing #Ebola virus circulation in the Tshuapa province (#DRC): A #OneHealth #investigation of wildlife and #human interactions

 

Abstract

The wildlife reservoir and spillover mechanisms of Ebola virus remain elusive despite extensive research efforts in endemic areas. This study employed a One Health approach to examine the virus’ circulation in wildlife and the associated human exposure risks in the Tshuapa province of the Democratic Republic of the Congo. We screened 1049 samples from 919 animals, predominantly small mammals, collected in 2021, and 380 samples from inhabitants of Inkanamongo village, the site of an Ebola virus disease outbreak in 2014. These samples were screened for evidence of current (RNA) or past (IgG antibodies) Ebola virus infections. We also conducted interviews with 167 individuals in the surrounding districts to assess their interactions with wildlife. While no Ebola virus RNA was detected in the wildlife samples, anti-orthoebolavirus IgG antibodies were found in 13 bats and 38 rodents. Among the human participants, 120 individuals had IgG antibodies against at least 1 orthoebolavirus antigen, with 12 showing seropositivity for 2 antigens of the same orthoebolavirus, despite not having a prior Ebola disease diagnosis. Furthermore, the majority of respondents reported frequent visits to the forest to hunt a variety of wild animals, particularly ungulates and rodents, which could account for occasional viral spillovers. The absence of active Ebola virus circulation in wildlife may reflect seasonal patterns in reservoir ecology, as those observed in bats. Similarly, seasonal human activities, such as hunting and foraging, may result in periodic exposure risks. These findings highlight the importance of continuous, multidisciplinary surveillance to monitor changes in seasonal spillover risks.

Author summary

Since its discovery in 1976 in the Democratic Republic of Congo (DRC), Ebola virus (EBOV) has caused more than 20 outbreaks in humans, with fatality rates as high as 90%. While the virus is believed to have an animal origin, naturalist reservoir and the mechanisms of transmission to humans remain poorly understood. Gaining insight into which species may harbour the virus and how transmission occurs is essential to predict and prevent future outbreaks. In this study, we investigate EBOV exposure in wildlife and humans in a region of the DRC with a documented history of outbreaks. Although we did not detect active infection in animals, we found serological evidence of prior exposure in several bat and rodent species, as well as among local residents. Interviews with community members revealed frequent contact with wildlife through hunting and handling, practices that could elevate the risk of animal-to-human transmission. These findings offer new clues about possible EBOV reservoirs and highlight the role of human behaviours in facilitating facilitate spillover events. Our results underscore the need for continued, integrated surveillance to improve understanding of Ebola virus ecology and to help reduce the risk of future Ebola outbreaks in endemic regions.

Source: 

Link: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1013628

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#Ethiopia confirms first #outbreak of #Marburg virus disease (#WHO AFRO, Nov. 15 '25)

 

14 November 2025

Addis Ababa—Ethiopia’s Ministry of Health has confirmed an outbreak of Marburg virus disease in the South Ethiopia Region, the first of its kind in the country, following laboratory testing of samples from a cluster of suspected cases of viral haemorrhagic fever.

Genetic analysis by the Ethiopia Public Health Institute revealed that the virus is of the same strain as the one that has been reported in previous outbreaks in other countries in East Africa. 

A total of nine cases have been reported in the outbreak that has affected Jinka town in the South Ethiopia Region.

The national authorities are scaling up response including community-wide screening, isolation of cases, treatment, contact tracing and public awareness campaigns to curb the spread of the Marburg virus, which is in the same family of viruses that cause Ebola virus disease.

The World Health Organization (WHO) and partners are supporting the government as it intensifies response to halt the spread of the virus and end the outbreak. A team of responders with expertise in viral haemorrhagic fever outbreak response has been deployed along with medical supplies and equipment.  

Marburg virus disease is a severe and often fatal illness caused by the Marburg virus. The disease is transmitted to humans from fruit bats and spreads among people through direct contact with bodily fluids of infected individuals or contaminated materials.

Initial symptoms include high fever, severe headache, muscle aches and fatigue. Many patients develop severe bleeding within a week of onset. Although several promising candidate medical countermeasures are currently undergoing clinical trials, there is no licensed therapeutic or vaccine for effective management or prevention of Marburg virus disease. However, early access to supportive treatment and care – rehydration with oral or intravenous fluids – and treatment of specific symptoms, improve survival.  

In the African region, previous outbreaks and sporadic cases have been reported in Angola, the Democratic Republic of the Congo, Ghana, Kenya, Equatorial Guinea, Rwanda, South Africa, Tanzania and Uganda.

Source: World Health Organization, Regional Office for Africa, https://www.afro.who.int/countries/ethiopia/news/ethiopia-confirms-first-outbreak-marburg-virus-disease

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RAPID #RISK #ASSESSMENT: #EBOLA VIRUS DISEASE, DRC (#WHO, September 19 '25)

 

{Summary}

Overall risk and confidence

Overall risk

-- National: High 

-- Regional: Moderate   

-- Global: Low   

Confidence in available information 

-- National: Moderate

-- Regional: Moderate

-- Global: Moderate

Risk statement

On 1 September 2025, WHO received an alert from the Ministry of Health of the Democratic Republic of the Congo (DRC) regarding suspected cases of Ebola virus disease (EVD) in the Bulape Health Zone, Kasai Province, DRC. 

The first currently known suspected EVD case was admitted to the Bulape General Reference Hospital on 20 August 2025 and reported to have died five days later (25 August 2025).

This is a 34-year-old female patient with a 34-week gestational age who presented with fever, bloody diarrhoea, followed by anal, oral, and nasal haemorrhage, vomiting, and asthenia. 

She reportedly died on 25 August 2025, with a clinical picture of multiple organ failure. 

Two of the contacts of this first case (a midwife and a laboratory technician) also developed similar symptoms and died a few days later.  

As of 4 September 2025, a total of 28 suspected cases, including 15 deaths (case fatality ratio: 54 %) had been reported from the Bulape health zone (Bulape, Bulape COM and Dikolo) and Mweka health zone. 

Among deaths, four are health care workers.  

In addition, 20% of the suspected cases are aged under 15 years. 

Five blood samples and one swab were collected from six suspected cases from the three health areas and arrived today at the National Public Health Laboratory (INRB) in Kinshasa for confirmation testing.

A crisis committee has been activated at the local and provincial levels, risk communication and active surveillance activities are underway, all cases are isolated, Infection Prevention and Control (IPC) measures are being implemented, isolation and contact tracing are underway, and patients are receiving intravenous medications, including ceftriaxone and metronidazole. 

The INRB confirmed Ebola virus (EBOV), Orthoebolavirus zairense species was detected through RTPCR assays, including GeneXpert, on 3 September.    

At national level, the risk is considered high due to:  

• Information gaps on the cases, including the first case, particularly: 

-- the date of symptom onset, 

-- their therapeutic itinerary, 

-- the potential number of contacts within the community, and 

-- epidemiological links between cases does not allow an assessment as to the extent of the outbreak. Similar alerts have been reported from this location/region in the past few months.  

• Most of the cases recorded so far in this health zone live in the Health Areas with a high population density and mobility. This could accelerate disease transmission within the community.  

• The last EVD outbreak in this health zone, Bulape, was in 2007, 18 years later, the capacities required for the response to a potential EVD outbreak may not exist.  

• So far, in addition to Bulape health zone, the epicentre of the outbreak, suspected cases are being reported in the neighbouring district of Mweka showing a potential geographic extension of the outbreak.   

• Bulape has a large market every Friday, attracting people from the surrounding villages. The city of Mweka borders a health district in the province of Kasai-Central (Bena Leka). Furthermore, population movements between Bulape and Tshikapa, the capital city of Kasai province, are frequent as part of trading activities.  Tshikapa city is considered as a regional market hub receiving populations from neighbouring provinces.  

At the regional level the risk is moderate due to the proximity of Bulape to Tshikapa city, the capital city of Kasai province and the Angolan border (approximately 100 to 200 kilometres depending on the nearest border crossing point) as well as population movement between Bulape and Tshikapa then Tshikapa and Angola.  

At the global level, the risk is low. 

(...)

Source: World Health Organization, https://www.who.int/publications/m/item/who-rapid-risk-assessment---ebola-virus-disease--democratic-republic-of-the-congo-v.1

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#Ebola virus’ hidden #target: virus #transmission to and infection of #skin

 

ABSTRACT

Ebola virus (EBOV), the causative agent of Ebola virus disease, remains one of the World Health Organization’s top 10 threats to global health. Infectious EBOV virions can be found on the surface of skin late in infection and may be transmitted to others through skin-to-skin contact. We investigate in vivo EBOV tropism and the kinetics of virus movement to and from the skin. Increasing viral loads were detected over time in the skin of EBOV-infected non-human primates and mice, with antigen detected in dermal stromal and immune cells. Epidermal cells within and surrounding hair follicles also harbored viral antigen, suggesting a novel mechanism of virus egress to the epidermal surface. During late infection, proinflammatory responses were elevated in infected visceral organs but minimal in the skin despite significant viral loads. We observed similar viral trafficking and cell tropism in the skin of mice intraperitoneally infected with a low containment EBOV model virus, rVSV/EBOV GP, allowing more detailed mechanistic studies. Sites of virus infection in the skin were patchy, with intense focal areas of infection surrounded by uninfected areas. To investigate virus entry into the body through skin, rVSV/EBOV GP was applied to the surface of gently abraded skin to remove the stratum corneum; epidermal keratinocytes were robustly infected with subsequent systemic viral dissemination observed in some mice. Optimal levels of infection within the skin required expression of the phosphatidylserine receptor, AXL. Collectively, our data demonstrate that skin serves as an important organ targeted by EBOV, facilitating virus entry into and egress from the body.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.01300-25?af=R

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#Marburg Virus #Disease in #Rwanda, 2024 — Public Health and Clinical Responses

 

Abstract

Background

On September 27, 2024, Rwanda reported an outbreak of Marburg virus disease (MVD), after a cluster of cases of viral hemorrhagic fever was detected at two urban hospitals.

Methods

We report key aspects of the epidemiology, clinical manifestations, and treatment of MVD during this outbreak, as well as the overall response to the outbreak. We performed a retrospective epidemiologic and clinical analysis of data compiled across all pillars of the outbreak response and a case-series analysis to characterize clinical features, disease progression, and outcomes among patients who received supportive care and investigational therapeutic agents.

Results

Among the 6340 patients with suspected MVD who underwent testing, 66 had laboratory-confirmed MVD, 51 (77%) of whom were health care workers. The median estimated incubation period was 10 days (interquartile range, 8 to 13), and symptom onset occurred a median of 2 days (interquartile range, 1 to 3) before hospital admission. The results of epidemiologic investigations were highly suggestive of a zoonotic origin of the outbreak: an index patient was identified who had been exposed to Egyptian fruit bats at a mining site. The case fatality rate in the outbreak was 23% (15 deaths among 66 patients). Remdesivir and the monoclonal antibody MBP091 were used under expanded access and clinical trial protocols. In addition, 1710 frontline workers and high-risk contacts received the chimpanzee adenovirus 3–vectored vaccine ChAd3-MARV under emergency use authorization in a phase 2 clinical trial.

Conclusions

Implementation of containment measures, advanced supportive care, and access to investigational countermeasures may have contributed to reduced mortality from MVD in this outbreak. Enhancing surveillance, improving infection prevention and control in health care settings, and ensuring timely deployment of medical countermeasures will be critical for mitigating the effects of future filovirus disease outbreaks.

Source: The New England Journal of Medicine, https://www.nejm.org/doi/full/10.1056/NEJMoa2415816?query=TOC

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Heterologous two-dose #Ebola #vaccine regimen in #pregnant women in #Rwanda: a randomized controlled phase 3 trial

 

Abstract

Risk of death for both mother and fetus following Ebola virus infection is extremely high. In this study, healthy women in Rwanda aged ≥18 years were randomized to two-dose Ebola vaccination (Ad26.ZEBOV, MVA-BN-Filo) during pregnancy (group A) or postpartum (group B). Unvaccinated pregnant group B women served as control. This was a parallel, randomized, controlled, open-label, single-center trial to evaluate the safety (primary endpoint—outcomes of interest and serious adverse events (SAEs)) and immunogenicity (secondary endpoint) of the two-dose Ebola vaccination. Among 3,484 women screened, 2,013 were randomized, and 2,012 women and 1,945 infants born alive were descriptively analyzed. Adverse outcomes of interest occurred in women (5.2% in group A and 7.3% in group B) and infants (26.0% in group A and 25.6% in group B). The most common maternal outcome of interest was pathways to preterm birth (3.2% in group A and 3.4% in group B), and the most common infant outcome of interest was small for gestational age (14.3% in group A and 11.8% in group B). Maternal/fetal and neonatal/infant SAE frequencies were comparable between groups (9.8% in group A, 9.0% in group B and 21.9% in group A, 15.9% in group B, respectively). Anti-Ebola virus glycoprotein-specific binding antibody response (secondary endpoint) was sustained in ≥90% of women at 1 year postdose 1. In group A, binding antibodies were detected in cord blood (99%) and infant serum (95%) samples 14 weeks postbirth. The trial met all primary and secondary objectives. Ad26.ZEBOV, MVA-BN-Filo did not raise concerns regarding adverse maternal/fetal or neonatal/infant outcomes, had no unexpected safety issues, and induced binding antibody responses in women and offspring through passive transfer. ClinicalTrials.gov registration: NCT04556526.

Source: Nature Medicine, https://www.nature.com/articles/s41591-025-03932-z

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Chapter One - #Mucosal #Sudan virus #infection results in a lethal disease in #ferrets with previous #Lloviu virus infection not providing cross-protection

Abstract

Sudan virus (SUDV) causes highly lethal outbreaks of hemorrhagic disease throughout Africa, but there has yet to be an approved vaccine or therapeutic to combat this public health threat. The most common route of natural exposure to filoviruses is through mucosal contact which greatly impacts initial viral replication. Historically, SUDV animal models used an intramuscular infection route. Here, we sought to further characterize an animal model using mucosal challenge routes and compared the impact that intramuscular, intranasal, or aerosol exposure had on SUDV pathogenicity in a ferret model. We determined that the route of infection did not significantly impact overall SUDV pathogenicity; only subtle changes were detected in magnitude of viremia and oral viral shedding. Additionally, we sought to determine if preexisting Lloviu virus (LLOV) immunity could protect ferrets from lethal SUDV infection. We found that the previous immunity elicited by LLOV infection was not sufficient to protect ferrets from lethal SUDV disease. In conclusion, our results indicate that the infection route has minimal effect on overall pathogenicity of SUDV in ferrets and that prior LLOV infection does not elicit a cross-protective immune response to SUDV.

Source: Advances in Virus Research, https://www.sciencedirect.com/science/article/abs/pii/S0065352725000077?via%3Dihub

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#Thermal #tolerance and #inactivation of #Ebola virus

{Summary}

HIGHLIGHTS

• The investigation demonstrated a high level of tolerance of EBOV to thermal disinfection.

• A water-bath is recommended and the tubes should be fully submerged during the process.

• The established inactivation guidelines should be followed very strictly.

Dear Editor,

Viruses of the genus Orthoebolavirus cause sporadic outbreaks of severe haemorrhagic fever, with case fatality rates ranging from 25% to 90% (Mahanty and Bray, 2004). Six species of the virus (Orthoebolavirus zairense, sudanense, bundibugyoense, taiense, restonense, and bombaliense) have so far been identified (Biedenkopf et al., 2023). Among these, Orthoebolavirus zairense, commonly known as Ebola virus (EBOV), stands out as the most virulent. Given its high contagiousness and lethality, EBOV must be manipulated under biosafety level 4 (BSL-4) conditions, as stipulated by the National Health Commission of the People's Republic of China's list of human pathogenic microorganisms. Prior to being removed from a BSL-4 laboratory, it is imperative that infectious EBOV undergoes complete inactivation. Here we systematically evaluate viral thermostability under BSL-4 containment conditions, demonstrating EBOV’s marked thermotolerance.

(...)

Source: Virologica Sinica, https://www.sciencedirect.com/science/article/pii/S1995820X25000975

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Monotherapy with #antibody 1C3 partially protects #Ebola virus-exposed #macaques

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-exposed macaques. Our findings highlight combination treatment with 1C11 as critical for protection, particularly against SUDV, and in vivo activity of unpartnered 1C3 as susceptible to rapid EBOV and SUDV escape under therapeutic pressure.

IMPORTANCE

A cocktail of human monoclonal antibodies 1C3 and 1C11 previously protected macaques exposed to a lethal dose of either Ebola virus (EBOV) or Sudan virus (SUDV). Since the unique binding characteristics of 1C3 are of particular interest, we evaluated its protective activity as monotherapy in macaques exposed to either EBOV or SUDV. Two doses of 1C3 alone did not protect SUDV-exposed macaques and only partially protected EBOV-exposed macaques. Importantly, failure to protect was associated with the rapid emergence of previously in vitro-identified escape mutations at the 1C3 binding site, highlighting the importance of its use in combination with 1C11 for protection against fatal disease outcome and avoiding rapid EBOV and SUDV escape. Findings have broader implications for the wise use of combination-based monoclonal antibody therapeutics to improve outcomes and prevent resistance in filovirid diseases.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.00296-25?af=R

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#Epidemiology and Genetic Characterization of Distinct #Ebola #Sudan #Outbreaks in #Uganda

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. 

The 2022 outbreak involved 164 confirmed cases and a case fatality rate (CFR) of 33.5%, with significant geographic variation in case distribution. The 2025 outbreak, still ongoing, was first detected in Kampala, with evidence of both nosocomial and community transmission. Phylogenomic analysis revealed the presence of two main genetic groups, representing Sudan and Uganda, respectively. The genetic variability of the Ugandan cluster is higher than that observed in Sudan, suggesting a greater expansion potential, which aligns with the current outbreak. Epidemiological findings indicate that human mobility, weaknesses in the health system, and delays in detection contribute to the amplification of the outbreak. 

Conclusions. 

Our findings underscore the importance of integrated genomic and epidemiological surveillance in understanding SUDV transmission dynamics. The recurrent emergence of SUDV highlights the need for improved outbreak preparedness, rapid response mechanisms, and international collaboration. Strengthening real-time surveillance and enhancing healthcare system resilience are critical to mitigating the impact of future outbreaks.

Source: Infectious Disease Reports, https://www.mdpi.com/2036-7449/17/3/44

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Single-dose replicon #RNA #Sudan virus #vaccine uniformly protects female guinea pigs from disease

Abstract

The Sudan virus (SUDV) outbreaks in Uganda in 2022 and 2025 created public health concerns in-country and the entire East African region. There are currently no licensed countermeasures against SUDV. We developed a SUDV vaccine candidate based on a nanocarrier (LIONTM) complexed with an alphavirus-based replicon RNA. Here, we compare the protective efficacy of the LION-SUDV vaccine either encoding the SUDV glycoprotein (GP) alone or in combination with the Ebola virus (EBOV) GP (LION-Combination). A LION-EBOV vaccine which is protective against EBOV was also included to determine the potential for cross-protection against SUDV infection. Single-dose vaccinations were conducted three weeks before challenge with a lethal dose of guinea pig-adapted SUDV using a female guinea pig disease model. We demonstrate 100% survival and protection with the LION-SUDV and the LION-Combination vaccines, while the LION-EBOV vaccine achieved 50% protection. Antigen-specific humoral responses correlate with decreased virus replication and survival. This result warrants further studies in larger animal species to ensure that protective efficacy is maintained with the single-dose LION-SUDV vaccine.

Source: Nature Communications, https://www.nature.com/articles/s41467-025-59560-1

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#Sudan virus disease - #Uganda (#WHO D.O.N., April 26 '25)

{Summary}

Situation at a glance

On 26 April 2025, the Ministry of Health (MoH) of Uganda declared the end of the Sudan virus disease (SVD) outbreak after two consecutive incubation periods (a total of 42 days) since the last person confirmed with SVD tested negative for the virus on 14 March 2025. 

A total of 14 SVD cases (including 12 confirmed cases and two probable cases) including four deaths (two confirmed and two probable) have been reported during this outbreak. 

WHO and partners provided technical, operational and financial support to the government to contain the outbreak. 

Although the outbreak has been declared over, health authorities are maintaining surveillance to rapidly identify and respond to any re-emergence. 

Risk communication and community engagement will also continue to ensure the community stay informed and stigma to those who were affected is minimized.

(...)

Source: World Health Organization, https://www.who.int/emergencies/disease-outbreak-news/item/2025-DON566

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#Remdesivir, mAb114, REGN-EB3, and #ZMapp partially rescue nonhuman #primates infected with a low passage #Kikwit variant of #Ebola virus

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 group. Our data show similar suboptimal efficacy of individual therapeutics in the uniformly lethal NHP model of EVD, supporting further clinical investigation of therapeutic combinations to maximize the overall therapeutic effect and improve patient outcomes, particularly for the treatment of advanced stage EVD.

Source: Nature Communications, https://www.nature.com/articles/s41467-025-59168-5

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