#Genome-informed structural #analysis of #polymerase and glycoprotein #adaptation in #H5N1 clade 2.3.4.4b

 

Abstract

Importance

Understanding the molecular mechanisms driving H5N1 clade 2.3.4.4b is critical for pandemic preparedness.

Objective

To characterize the molecular drivers of viral fitness and mammalian adaptability in recent H5N1 viruses by integrating evolutionary dynamics with structural simulations.

Methods

This study analyzed 2,398 H5Nx genomes (2000–2024) through phylogenetic and selective pressure analyses. HA/NA structures were predicted with AlphaFold 3 and evaluated by AutoDock4 docking, whereas polymerase–ANP32A/B complexes were modeled using template-based methods and their binding free energies were estimated using MM/GBSA. Polymerase–ANP32E complexes were predicted with AlphaFold 3 and similarly evaluated by MM/GBSA. The binding affinities (ΔG) for the sialic acid (SA) receptors and human ANP32 proteins were quantified through molecular mechanics/generalized born surface area calculations.

Results

Clade 2.3.4.4b showed significant antigenic drift in the HA receptor binding site, reducing affinity for α2,3-SA and α2,6-SA receptors. On the other hand, the emergence of a full-length stalk N1 NA with second sialic acid-binding site mutations (e.g., N366S) compensated for reduced HA affinity by enhancing the NA binding stability. In the polymerase complex, both the PB2-627E/631L variant (−144.00 kcal/mol; unadjusted p = 0.0058) and the known mammalian-adaptive 627K/631M variant (−144.67 kcal/mol; unadjusted p = 0.0165) showed more favorable predicted human ANP32B binding free energies than the ancestral 627E/631M state (−136.46 kcal/mol).

Conclusions and Relevance

The co-occurrence of HA, NA, PB1, and PB2 signatures was associated with clade expansion and produced structural predictions consistent with altered receptor or ANP32 interactions; experimental validation is required before inferring effects on fitness or zoonotic risk.

Source: 

Link: https://vetsci.org/DOIx.php?id=10.4142/jvs.26088

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The first high pathogenicity avian #influenza #H5N1 clade 2.3.4.4b incursions in Hunter New England region, NSW, #Australia, June–July 2026

 

Abstract

Two incursions of high pathogenicity avian influenza (HPAI) A(H5N1) clade 2.3.4.4b in vagrant birds were identified in the Hunter New England region of New South Wales, Australia on 28 June 2026 and 10 July 2026. These were the first detections of the virus in New South Wales and occurred shortly after the first Australian detection in June 2026. The Hunter New England Population Health Unit managed human contacts of the infected birds using a contact management system designed and purpose-built by the Unit. We report on the public health response and opportunities for improvement.

Source: 

Link: https://ojs.cdi.cdc.gov.au/index.php/cdi/article/view/3492

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#Report on #influenza viruses received and tested by the #Melbourne #WHO Collaborating Centre for Reference and Research on Influenza during 2025

 

Abstract

As part of its role in the World Health Organization (WHO) Global Influenza Surveillance and Response System (GISRS), the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne (the Centre) received 13,817 human influenza-positive samples during 2025. Viruses were analysed for their antigenic, genetic, and antiviral susceptibility properties. Selected viruses were propagated in qualified cells or embryonated hens’ eggs for potential use in seasonal influenza virus vaccines. Of the 13,817 samples received or processed, influenza A(H1N1)pdm09 viruses predominated, accounting for 46.1% of samples, compared to 21.2% for A(H3N2) viruses and 19.5% for influenza B viruses; one influenza C virus was received. Among viruses analysed at the Centre, the majority of A(H1N1)pdm09 (> 99%) and influenza B (98%) viruses were antigenically similar to their respective WHO recommended vaccine strains for the Southern Hemisphere in 2025. In contrast, only 43% of A(H3N2) viruses were antigenically similar to their respective WHO recommended vaccine strains. Of 3,307 samples tested for susceptibility to the neuraminidase inhibitors oseltamivir and zanamivir, 37 A(H1N1)pdm09 viruses showed highly reduced inhibition by oseltamivir and no influenza viruses tested showed highly reduced inhibition by zanamivir. Of 5,080 samples with sequencing of the polymerase acidic (PA) gene, no genetic markers associated with highly reduced susceptibility to baloxavir marboxil were identified.

Source: 

Link: https://ojs.cdi.cdc.gov.au/index.php/cdi/article/view/3489

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#Nirmatrelvir–ritonavir targeting viral #persistence in post-COVID-19 condition (long #COVID) in the #USA (RECOVER-VITAL): a randomised, double-blind, placebo-controlled, phase 2 trial

 

Summary

Background

Post-acute sequelae of SARS-CoV-2 infection, more commonly known as long COVID, has emerged as a major health problem. The pathogenesis of long COVID is unknown, but among the leading hypotheses is viral persistence. We aimed to investigate whether the use of the SARS-CoV-2 antiviral nirmatrelvir–ritonavir improved long COVID symptoms.

Methods

We conducted a double-blind, placebo-controlled, randomised trial involving adults who had developed persistent symptoms (≥12 weeks) associated with three major symptom phenotypes (cognitive, autonomic, or exercise) after acute SARS-CoV-2 infection at 69 US sites. Participants were eligible if they were 18 years or older and had a previous suspected, probable, or confirmed SARS-CoV-2 infection, as defined by the Pan American Health Organization. Eligible participants were also required to have either at least two moderate symptoms from the same phenotype or one severe phenotype-associated symptom, as identified with the Cluster Targeted COVID-19 Symptom Questions. Participants were randomly allocated in a double-blind manner in a 1:1:1 ratio using permuted blocks of size 30 to receive either 15 days of active intervention followed by 10 days of placebo (300 mg nirmatrelvir–100 mg ritonavir twice daily, then 100 mg ritonavir–placebo); 25 days of active intervention (300 mg nirmatrelvir–100 mg ritonavir twice daily); or 25 days of placebo–ritonavir (100 mg ritonavir–placebo). A clinically significant change in patient-reported outcomes at day 90 comprised the primary endpoint: Patient-Reported Outcomes Measurement Information System Cognitive Function Short Form 8a, Orthostatic Hypotension Questionnaire question 1, and a modified version of the DePaul Symptom Questionnaire Post-Exertional Malaise short form. Secondary outcomes were phenotype-specific performance measures. The study was registered at ClinicalTrials.gov (NCT05595369) and is complete.

Findings

Between July 27, 2023, and Sept 6, 2024, 1207 individuals were screened. Of these, 964 were randomly allocated and 959 participants, excluding four participants who were later found ineligible and one who did not initiate treatment, were enrolled in the three phenotypes: 332 to cognitive, 334 to autonomic, and 332 to exercise. In the 959 participants in the mITT population, 643 (67%) self-reported as female, 314 (33%) were male, and two participants had a sex of unknown or undifferentiated; 750 (78%) were White; and 108 (11%) were Hispanic, Latino, or Spanish. The median age was 49 years (IQR 38–59). No statistically significant benefits were observed for any phenotype for primary endpoints. For the cognitive phenotype, adjusted differences compared to placebo were 3·2% (95% CI –10·4 to 16·8, p=0·65) for the 25-day regimen and –2·2% (–15·5 to 11·1, p=0·74) for the 15-day regimen. For the autonomic phenotype, adjusted differences were –6·4% (–18·5 to 5·7, p=0·30) for the 25-day regimen compared to placebo and –0·1% (–12·5 to 12·3, p=0·99) for the 15-day regimen compared to placebo. For exercise, adjusted differences were –7·8% (–19·5 to 3·8, p=0·19) for the 25-day regimen compared to placebo and 0·9% (–11·4 to 13·2, p=0·88) for the 15-day regimen compared to placebo. There were no differences in secondary endpoints, and no safety signals were observed; there were no deaths, and 52 serious adverse events occurred in 42 (4%) of 963 participants over the course of the study.

Interpretation

Nirmatrelvir–ritonavir for 15 days or 25 days showed no evidence of benefit in long COVID in any of the three phenotypes studied. These findings suggest additional approaches to measuring the symptom burden and treating Long COVID are needed.

Funding

National Institutes of Health.

Source: 

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(26)00406-8/fulltext

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#Bundibugyo at the #Border: The 2026 #Ebola #Outbreak and the Case for Pre-emptive #Countermeasure #Equity

 

Abstract

The 2026 Ebola outbreak caused by Bundibugyo ebolavirus in the Democratic Republic of the Congo and Uganda exposes a persistent structural flaw in global health security: preparedness remains overwhelmingly reactive and pathogen-specific. Despite the $518 million Africa CDC-WHO joint continental plan, no licensed BDBV vaccine or therapeutic is available; a 21-day (three-week) detection delay and cross-border transmission expose inadequate inter-epidemic investment in non-Zaire ebolavirus countermeasures. We argue for sustained, ring-fenced financing, institutionalised cross-border coordination, species-inclusive diagnostics, and real-time genomic data sharing to move African Ebola preparedness from reactive to pre-emptive.

Source: 

Link: https://www.sciencedirect.com/science/article/pii/S1477893926000682?via%3Dihub

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#Antibody profiles across #H5N1 and previously circulating viruses are highly dynamic and #age- and imprint- independent

 

Abstract

The increasing incidence of H5N1 influenza virus transmission from animal species to humans has heightened concerns about an imminent H5N1 pandemic. Prior studies using recombinant hemagglutinin and neuraminidase proteins have reported age-dependent cross-reactivity to H5N1, attributed to immune imprinting from an individual's first influenza virus exposure. However, whether this pattern holds when using whole inactivated virus (WIV), capturing antibodies against diverse viral proteins, and is stable over time remains unknown. We therefore aimed to determine whether H5N1 cross-reactivity of pre-existing antibodies to whole virus follows an age-dependent or imprinting-specific pattern, and whether this pattern is stable over a five-year period. To this end, we measured serum antibody levels in adolescents, adults and seniors by ELISA using whole inactivated H5N1 virus as antigen rather than purified proteins. Detectable, albeit generally low, levels of H5N1-reactive antibodies were present in most individuals, irrespective of age. Comparison of antibody levels against H5N1 with those to five historical influenza virus strains revealed a consistent positive correlation between H5N1-reactive antibodies and responses to the H1N1pdm09 strain A/California/7/2009 (CA), across all age groups. Using unbiased clustering of antibody titers against H5N1, CA, and the H3N2 strain A/Perth/16/2009 (PE), we identified seven distinct age-transcending antibody profiles. These profiles covered individuals with varying titers to all three included viruses but also identified individuals with high anti-CA levels, yet low anti-H5N1 levels and vice versa. Moreover, despite stable antibody levels over a five-year interval in the study population, individual antibody levels and profiles fluctuated considerably over this period. Taken together, our results confirm the presence of H5N1-reactive antibodies in human sera and their association with previously circulating strains. However, they also caution against inferring antibody levels against a new strain based solely on responses to antigenically related strains and highlight the limitations of extrapolating immune status from single timepoint measurements.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.medrxiv.org/content/10.64898/2026.08.26.26361396v1

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Acute #Protein Responses Control #SARS-CoV-2-specific #Neurocognitive and General Post-Viral #Sequelae

 

Abstract

Post-acute infection syndromes (PAIS) follow viral syndromes including post-acute sequelae of COVID19 (PASC) which complicates 10-25% of SARS-CoV-2 infections. These syndromes lack precise explanatory mechanisms. We studied 173 human saliva proteomes during respiratory viral syndromes, seeking associations between 44 clinically-relevant protein expression patterns and subsequent sequelae counts. Exploratory models adjusted by extensive clinical annotations found interactions between 23 acutely-responsive proteins and SARS-CoV-2 infection that inversely predicted subsequent neurocognitive sequelae. An overlapping 19 acutely-responsive proteins during any acute respiratory viral syndrome inversely predicted general fatigue-related sequelae. Altogether, 29 proteins, derived from interferon stimulated genes (ISG), were uniformly beneficial, including 13 predictive of both neurocognitive and general sequelae. The proteins suggested both shared early pathobiology and virus-specific protective responses that shaped resolution of acute disease and different PAIS. Acutely elevated protective ISG proteins associated with reduced post-viral symptoms identify investigational starting points for novel mechanisms, diagnostics and therapeutics for PASC and PAIS.

Competing Interest Statement

Theodore G. Liou, Judy L Jensen and Kristyn A Packer received research funding from Anagram, Aridis, BioMX, Calithera, Clarametyx, Gilead, Insmed, Laurent, Novartis, the US Cystic Fibrosis Foundation′s Therapeutic Development Network and Vertex for performance of clinical studies during the study period. Bricelyn H Strauch maintains the copyright for Figure 3. Theodore Liou and Frederick Adler, through the University of Utah, are named as inventors on the following patent applications related to the proteins identified in this manuscript: (1) a provisional patent application titled ″DIAGNOSTICS AND TREATMENTS FOR ACUTE AND POST-VIRAL DISEASE BASED ON INNATE IMMUNE RESPONSES TO SARS-COV-2 INFECTION,″ serial number 63/792,687, filed 4/22/2025; (2) a provisional patent application titled ″ADDITIONAL INNATE IMMUNE RESPONSES WITH DIAGNOSTIC AND TREATMENT POTENTIAL FOR POST-ACUTE SEQUELAE OF COVID19 SYNDROME AND FOR POST-ACUTE INFECTION SYNDROME,″ serial number 63/979,883, filed 2/10/2026; (3) a Patent Cooperation Treaty (PCT) application titled ″METHODS FOR PREDICTING POST-ACUTE SEQUELAE OF VIRAL INFECTIONS USING INTERFERON STIMULATED GENE PROTEINS,″ serial number PCT/US2026/024520, filed 4/21/2026, which incorporates subject matter from (1) and (2); and (4) a provisional patent application titled ″ADDITIONAL ACUTELY EXPRESSED PROTEINS PROTECTIVE AGAINST NEUROCOGNITIVE AND GENERAL POST-VIRAL SEQUELAE,″ serial number 64/102,461, filed 6/30/2026. The applicant on all applications is the University of Utah.

Source: 

Link: https://www.medrxiv.org/content/10.64898/2026.08.27.26361488v1

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#Immunity Interrupted: Links Between #SARS-CoV-2 and the #Tripledemic of 2022

 

Highlights

    • SARS-CoV-2 infection was associated with fewer subsequent respiratory viral infections in children.

    • Children with prior SARS-CoV-2 infection had a longer interval before reinfection than those with other respiratory viral illnesses.

    • Rates of respiratory viral coinfection were lower following SARS-CoV-2 infection compared with other viral infections.

    • Prior SARS-CoV-2 infection was not associated with increased susceptibility to recurrent respiratory viral infections.

    • Findings support a potential role for viral interference and post-infection immune modulation in respiratory virus dynamics.

Abstract

Background

The post-pandemic resurgence of respiratory viral infections, commonly referred to as the "tripledemic," raised concerns that prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may increase susceptibility to subsequent respiratory illnesses. However, the relationship between SARS-CoV-2 infection and future respiratory viral infections in children remains poorly understood.

Objectives

To determine whether pediatric patients with SARS-CoV-2 infection were at increased risk of subsequent respiratory viral infections within 120 days compared with children diagnosed with other respiratory viral infections and to evaluate coinfection frequency and clinical outcomes.

Study Design

We conducted a retrospective cohort study of pediatric patients aged 6 months to <18 years presenting to emergency departments within a large healthcare system between January 1, 2021, and December 31, 2023. Patients were categorized as SARS-CoV-2 only (n=4,004), SARS-CoV-2 with respiratory viral coinfection (n=1,678), or other respiratory viral infection only (n=31,434). Patients were followed for 120 days after the index encounter. Primary outcomes included subsequent respiratory viral infections and laboratory-confirmed reinfections. Secondary outcomes included coinfection rates, oxygen supplementation, mechanical ventilation, and hospital length of stay.

Results

A total of 37,116 pediatric patients met inclusion criteria. Subsequent respiratory viral infections occurred less frequently among patients with SARS-CoV-2-only infection (4.4%) compared with patients with SARS-CoV-2 coinfection (6.0%; OR 1.39, 95% CI 1.08–1.79) and those with other respiratory viral infections (6.1%; OR 1.43, 95% CI 1.22–1.68). The mean time to subsequent infection was longest in the SARS-CoV-2-only group (68.4 days) compared with the SARS-CoV-2 coinfection (60.8 days) and other viral infection groups (58.8 days). Laboratory-confirmed reinfections occurred in 2.0% of patients with SARS-CoV-2-only infection and 2.8% of patients in both comparison groups. Coinfections were less common among patients with SARS-CoV-2 infection than among those with other respiratory viral infections. Severe clinical outcomes were uncommon across all groups. Although patients with SARS-CoV-2-only infection had slightly longer hospital stays and higher rates of mechanical ventilation, absolute event rates remained low.

Conclusions

Prior SARS-CoV-2 infection was not associated with an increased risk of subsequent respiratory viral infections in children. Instead, SARS-CoV-2 infection was associated with fewer subsequent infections, lower coinfection rates, and a longer interval before reinfection compared with other respiratory viral illnesses. These findings support the possibility of viral interference or transient immune-mediated protection following SARS-CoV-2 infection and suggest that factors other than prior SARS-CoV-2 infection were more likely responsible for the increased burden of respiratory viral illnesses observed during the post-pandemic period.

Source: 

Link: https://www.sciencedirect.com/science/article/abs/pii/S1386653226000855?dgcid=rss_sd_all

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Isolation and characterisation of #Nipah virus neutralising candidate therapeutic monoclonal #antibodies from an #mRNA-immunised pig

 

Abstract

Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus with epidemic potential. Despite the threat NiV poses, no therapeutics are licensed to treat infection. Studies have shown that monoclonal antibodies (mAb) can protect animals against NiV and the related Hendra virus (HeV). The best studied mAb, m102.4, has been used to treat infected patients on a compassionate basis, and has entered clinical trials. However, there is a need to define additional mAbs with therapeutic potential, which could be combined with m102.4 to improve neutralising potency and breadth. Here, we isolated five high affinity mAbs from an mRNA immunised pig, which bound the G glycoprotein derived from NiV Malaysia strain (NiV-M), and one of which (mAb A2) also bound HeV G. Aligned with this, all mAbs neutralised NiV-M pseudovirus but only mAb A2 neutralised pseudovirus representing the NiV Bangladesh (NiV-B) strain. mAb A2 and the most potent NiV-M neutralising mAb, C1, showed minimal competition with each other and m102.4, suggesting recognition of non-overlapping epitopes. Single-particle cryogenic electron microscopy of the NiV-M G receptor binding domain complexed to A1 and C2 Fab fragments revealed distinct epitopes that did not overlap with the receptor-binding site, targeted by m102.4, suggesting action through steric impedance of receptor binding or interference downstream of receptor engagement. Inoculation of mAb A2 to hamsters did not provide complete protection against NiV-B challenge (60% survival), however, a split dose of mAb A2 and m102.4 provided the same protection as m102.4 alone (100% survival). Collectively, these data demonstrate the potential of the porcine model for isolation of therapeutic candidate mAbs, which contribute both to our understanding of the NiV G antigenic landscape, and the development of mAb combinations, that exert complementary mechanisms of neutralisation, for therapeutic intervention.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

European Commission, https://ror.org/00k4n6c32, VetBioNet, EMJMD LIVE

Innovate UK, 971555

UK Research and Innovation, BBS/E/I/00007031, BBS/E/I/00007037, BBS/E/I/00007038, BBS/E/I/00007039, MR/S007555/1, BB/T008784/1

Wellcome Trust, 203141/Z/16/Z

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.08.28.745669v1?rss=1

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#Influenza A virus #H5N1 genotypes #B3.13 and D1.1 show #temperature-dependent restriction of #replication in primary #human respiratory epithelial cell cultures derived from the upper and lower respiratory tract

 

Abstract

H5N1 clade 2.3.4.4b avian influenza A viruses pose a significant threat to wild animal populations, domesticated animals, and potentially, the human population. For H5N1s to infect and transmit among mammalian species, mutations for improved utilization of mammalian receptors and enhanced replication at the lower temperatures of the upper respiratory tract need to be acquired. A human H1N1pdm09-like virus was compared to H5N1 genotypes B3.13 and D1.1 for replication at 33ºC, 37ºC, and 39ºC – temperatures consistent with the upper and lower respiratory tract in humans, and dairy cow udder tissue. All H5N1 viruses had increased plaque sizes on MDCK cells at 37ºC and 39ºC compared to H1N1pdm09. In primary, differentiated human nasal and bronchial epithelial cultures, all H5N1 viruses show restricted infectious virus production compared to H1N1 at 33ºC. While H5N1 D1.1 also showed restricted replication at 37ºC and 39ºC, the H5N1 B3.13 replicated to nearly equivalent titers as H1N1pdm09. All H5N1 viruses demonstrated similar cell tropism in cells from the upper and lower respiratory tract, infecting more ciliated than non-ciliated cells relative to H1N1pdm09. H1N1, H5N1 B3.13 D1.1 infection induced similar innate immune factors, with nasal epithelial cells producing higher levels compared to bronchial epithelial cells. These data suggest that genotype B3.13 and D1.1 H5N1 viruses show different temperature dependent replication patterns compared to H1N1pdm09.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.08.27.747488v1

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Modeling the #impact of respiratory disease #outbreaks on the #US #agricultural #workforce

 

Abstract

Background: 

Emerging respiratory disease outbreaks pose a major threat to food production systems. Agricultural workers face health disparities that amplify their susceptibility to respiratory pathogens, yet the consequences for worker health and food production remain poorly understood. 

Methods: 

We developed a household-structured susceptible-infectious-recovered (SIR) transmission model to compare disease dynamics between agricultural workers and the general U.S. population across six regions. We simulated outbreaks across a range of epidemiological scenarios and assessed productivity losses in California for three labor-intensive crops (oranges, iceberg lettuce, strawberries) with different harvest seasonalities. 

Results: 

We show that, for a baseline reproduction number of R0 = 2.0, the peak disease prevalence among agricultural workers is 1.41-1.69 times higher than that of the general population across regions, and final outbreak sizes are 1.29-1.42 times higher. Household structure accounts for 54%-68% of the disease disparity. Peak productivity losses range from 0.50%-0.63% across crops, translating to millions in lost potential revenue. At higher transmissibility and severity (R0 = 3 and assuming all infections are symptomatic), losses are 2.4 times higher. 

Conclusions: 

Household crowding may lead to disproportionate respiratory disease burden among agricultural workers that is exacerbated by vaccination and obesity disparities, highlighting the need for targeted outbreak preparedness and mitigation strategies in the agricultural sector to maintain food system resilience and support public health in these communities.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.medrxiv.org/content/10.64898/2026.03.31.26349871v2

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Operational #epidemiology of the early phase of the 2026 #Bundibugyo virus disease #outbreak in the #DRC and #Uganda

 

Abstract

The 2026 Bundibugyo virus disease outbreak in the Democratic Republic of the Congo (DRC) and Uganda occurred in a fragile cross-border setting marked by delayed recognition, diagnostic uncertainty, insecurity, population mobility, community mistrust, and healthcare-worker exposure. We conducted a retrospective operational epidemiology study using official situation reports, public health declarations, ministry statements, WHO and Africa CDC updates, cross-border communiqués, and selected partner statements. This analysis reflects publicly available data from the early outbreak period, with the primary DRC data lock on 27 May 2026 and Uganda and regional triangulation through 29 May 2026. We reconstructed the early timeline, described epidemiological and geographic progression, quantified response indicators, and applied a transparent health-zone prioritization framework. The earliest documented symptom onset was 24 April 2026. The Institut National de Recherche Biomédicale (INRB) detected non-Zaire ebolavirus in eight of 13 samples on 14 May, giving a 20-day symptom-onset-to-first-laboratory-detection interval; species-level Bundibugyo virus confirmation and official declaration followed on 15 May. By the DRC data lock on 27 May, 125 confirmed cases and 17 confirmed deaths had been reported, giving a confirmed case fatality ratio of 13.6%. DRC also reported 906 suspected cases and 223 suspected deaths, giving a suspected fatality proportion of 24.6%. Confirmed cases expanded from three to 13 health zones across three provinces within 12 days. Ituri province accounted for 110 confirmed cases (88.0%); Bunia, Rwampara, and Mongbwalu health zones together contributed 90 cases (72.0%). Uganda reported nine confirmed cases and one death by 29 May. Operational pressure included 2,635 listed contacts in DRC, 436 contacts under follow-up in Uganda, and 126 of 774 collected samples (16.3%) pending testing in DRC. Healthcare workers represented 16 of 125 DRC confirmed cases (12.8%) and at least three of nine Uganda cases (33.3%). Applying the health-zone prioritization framework, Rwampara, Mongbwalu, and Bunia were classified as higher priority health zones. Excluding confirmed burden did not change any health-zone tier; data classification confidence was high for 10 zones and moderate for three. Within this early operational snapshot, outbreak visibility reflected both transmission and operational factors, particularly detection delay, laboratory backlog, cross-border movement, healthcare-linked exposure, and community trust or security incidents. The framework provides a transparent basis for rapid decision support during an outbreak’s early phase by directing surveillance, laboratory, case-management, infection prevention and control, contact-tracing, and community-engagement resources toward health zones where multiple operational risks converge.

Source: 

Link:https://journals.plos.org/globalpublichealth/article?id=10.1371/journal.pgph.0006680

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Pre-existing systemic and #nasal #antibodies against avian #H5 #influenza A viruses vary according to childhood #imprinting

 

ABSTRACT

Avian influenza A viruses (IAVs) pose a constant pandemic threat, with the recent 2.3.4.4b clade of the H5 subtype causing high pathogenicity and spreading across animal species and geographic locations. Understanding human pre-existing immunity to avian H5 IAV can inform on population susceptibility, a critical aspect of pandemic preparedness. To that end, we analyzed the IAV HA-specific antibodies across individuals born between 1928 and 1999 with different early life exposures to IAV subtypes. Individuals born prior to 1957 had the highest pre-existing serum antibodies to group 1 HA antigens, including the 2.3.4.4b H5 and a group 1 HA stem antigen. These birth year-specific patterns were not reflected in the limited pre-existing serum neutralizing antibodies detectable against a 2.3.4.4b H5 IAV or in H5-specific memory B cell populations. They were, however, evident in pre-existing nasal IgG and IgA titers to H5, which were greater in individuals born prior to 1957. Our findings demonstrate that the immunological biases afforded by early life exposure extend to antibodies detected in the nasal mucosa, the site of IAV replication.

Source: 

Link: https://journals.asm.org/doi/10.1128/mbio.01892-26

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West African Clade C #MERS-CoV Strains BF785 and Mor213 Induce More Robust #Interferon and Inflammatory Signaling Compared to Clade A in #Human Respiratory Cells

 

Abstract

Clade A Middle East respiratory syndrome coronavirus (MERS-CoV) spilled over from camels into humans in Saudi Arabia in 2012 and caused pneumonia and severe respiratory disease, with a 37% case fatality rate. While clade A and B viruses are closely related phylogenetically, clade B MERS-CoV strains have since outcompeted clade A strains and continue to circulate in camels and humans in the Middle East and cause outbreaks in humans. Clade C strains circulate in camels across the African continent but have not been reported to cause disease in humans. We have shown that a number of East African clade C isolates are less able to utilize the TMPRSS2-mediated pathway for viral entry in both cell lines and primary nasal epithelial cultures, which may underlie the reduced replication of East African clade C strains in humans. However, the reduced replicative capacity of West African strains in human cells appears to be independent of viral entry, suggesting an alternative basis for their attenuation. Here, we report that West African clade C MERS-CoV isolates with deletions in ORF4b encoding a key accessory protein, NS4b, induced significantly more robust interferon and inflammatory responses than clade A MERS in human respiratory cell lines and primary bronchial air–liquid interface cultures. The replication deficit for the West African strain BF785, which has a complete deletion of ORF4b, was partially rescued when RNASEL was knocked out in A549 cells. These findings demonstrate that complete loss of NS4b results in stronger innate immune activation than partial truncation and suggests that differential selection on NS4b may contribute to the varying phenotypes of clade C MERS-CoV strains circulating in African camels.

Source: 

Link: https://www.mdpi.com/1999-4915/18/9/935

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A cross-sectional #study of avian #influenza virus in #poultry #markets of #Guangdong #China, 2025

 

Abstract

Background: 

Guangdong, China is a critical epicenter for avian influenza virus (AIV) emergence, where H5N1 and highly pathogenic H7N9 were first identified. Monitoring AIV genotype distribution and genetic diversity in this region is essential for providing early warnings and mitigating the risk of human infections.

Methods: 

In May 2025, a cross-sectional study was conducted across 4 representative cities in Guangdong. We collected 500 environmental swabs and 45 wastewater samples from 23 live poultry markets (LPMs). Samples were screened for influenza A virus (IAV) and subtyped for H5, H7, and H9. Next generation sequencing (NGS) and phylogenetic analyses were employed to characterize viral diversity and zoonotic potential.

Results: 

AIV was detected in 49.2% (246/500) of environmental samples. H9 was the dominant subtype (38.2%), followed by H5 (3.2%) and H7 (0.8%); 2.4% of positive samples showed multi-subtype co-occurrence. “Non-restricted zone” markets (80.0%) and “waste storage areas” (68.4%) were identified as primary contamination hotspots. Phylogenetic analysis revealed that H5 and H9 viruses are accumulating mutations linked to enhanced human-type receptor affinity. Notably, H5 and H6 sequences exhibited long internal branches and clustered with isolates from other Asian countries rather than domestic strains, highlighting a significant gap in current domestic molecular surveillance and a lack of continuous evolutionary data for these genotypes.

Conclusions: 

Widespread AIV contamination persists in Guangdong LPMs, dominated by H9 with low-level circulation of highly pathogenic subtypes. The identified surveillance gaps for H5/H6 and the presence of multi-subtype environments underscore the urgent need for strengthened, integrated molecular monitoring and stricter market regulation to mitigate public health risks.

Source: 

Link: https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2026.1914072/full

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#Bundibugyo virus #glycoprotein seroreactivity following recombinant VSV–Zaire #Ebola virus glycoprotein #vaccination in outbreak-affected populations of #DRC: a longitudinal cohort study

 

Summary

Background

There are currently no licensed vaccines for disease caused by Bundibugyo virus (BDBV). The recombinant vesicular stomatitis virus–Zaire Ebola virus glycoprotein (rVSVΔG-ZEBOV-GP) vaccine has been widely deployed during Ebola virus disease outbreaks caused by Ebola virus (EBOV). Human studies have shown cross-reactive BDBV antibody responses following licensed Ebola virus disease vaccine administration, but the durability and longitudinal kinetics of these responses in populations vaccinated during outbreaks remain unknown. We aimed to evaluate BDBV glycoprotein seroreactivity following rVSVΔG-ZEBOV-GP vaccination in two longitudinal cohorts from regions of the Democratic Republic of the Congo affected by Ebola virus disease outbreaks.

Methods

This longitudinal cohort study was done in Mbandaka, Equateur Province, and Beni, North Kivu Province. Individuals aged 1 year and older who received the rVSVΔG-ZEBOV-GP vaccine under the WHO ring-vaccination protocol were eligible for enrolment. These populations were defined as: people with confirmed Ebola virus disease, contacts of people with Ebola virus disease or contacts-of-contacts, and health-care or front-line workers in areas affected by Ebola virus disease. Participants were enrolled from June 2 to July 3, 2018, in Mbandaka and from Aug 15 to 29, 2018, in Beni. Serum samples were collected from vaccine recipients and antibody reactivity was assessed using a multiplex pan-filovirus immunoassay. Both cohorts were followed up over 5 years, with seven data collection periods in each province. We evaluated longitudinal trends in EBOV and BDBV glycoprotein seroreactivity using a pan-filovirus multiplex immunoassay across follow-up visits.

Findings

We analysed 5849 serum samples from 1081 participants. 715 (66%) of 1081 participants were male and 366 (34%) were female. BDBV glycoprotein seroreactivity differed substantially between study sites. At baseline, 16 (3%) of 482 participants in Mbandaka and 62 (10%) of 599 in Beni were seroreactive to BDBV glycoprotein. In Mbandaka, BDBV glycoprotein antibody reactivity remained stable through to 6 months after initial vaccination before increasing from a mean median fluorescent intensity (MFI) of 1238 (SD 1599) at 2·5 years, with 16 (5%) of 355 seroreactive, to 4845 (5881) at 3·5 years and 116 (35%) of 329 seroreactive (p<0·0001), followed by waning at later visits. In Beni, BDBV glycoprotein antibody reactivity increased rapidly after the initial vaccination, with seroreactivity peaking at 21 days to a mean MFI of 6678 (SD 6997) with 283 (52%) of 541 participants seroreactive and at 6 months to an MFI of 6852 (6560) with 270 (54%) of 501 seroreactive. Although antibody levels decreased after 6 months, EBOV glycoprotein and BDBV glycoprotein antibody reactivity remained above baseline through to 5 years after vaccination.

Interpretation

The differing patterns of BDBV glycoprotein seroreactivity observed between Beni and Mbandaka warrant further investigation into the epidemiological and immunological factors associated with this seroreactivity, including the epidemiological significance of baseline seroreactivity observed before vaccination. To our knowledge, these findings provide the first longitudinal human data describing BDBV glycoprotein seroreactivity following licensed Ebola virus disease vaccination in populations living in regions now affected by the current outbreak of disease caused by BDBV. They add to the growing body of human evidence describing cross-reactive antibody responses following licensed Ebola virus disease vaccination and support rigorous clinical evaluation of rVSVΔG-ZEBOV-GP during the ongoing outbreak while BDBV-specific vaccines continue to be developed.

Funding

The US Food and Drug Administration, the Gates Foundation, and the US Defense Advanced Research Projects Agency.

Source: 

Link: https://www.sciencedirect.com/science/article/pii/S0140673626016089?dgcid=rss_sd_all

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Highly persistent #antibody levels but limited population #immunity in #gannets after #HPAI #outbreak

 

Abstract

The recent large-scale circulation of High Pathogenicity Avian Influenza (HP AI) viruses H5Nx of clade 2.3.4.4b has been responsible for massive die-offs in wild species, notably in long-lived seabirds, with unknown implications for the immunity of surviving individuals. In the North Atlantic, northern gannet colonies were heavily affected in 2022, with more than 40% mortality observed among breeding adults and some surviving individuals developing dark irises. Using samples collected in 2023 and 2024 on Rouzic colony (France), we report persistent individual anti-AI antibody levels and seroneutralisation titres, with most of the immune individuals showing dark irises. A modelling approach further stressed the importance of long-lasting immunity in such species by showing that the proportion of individuals which kept their immunity between years strongly limited decreases in population size in case of repeated outbreaks. Overall, our results highlight the existence and importance of long-lasting immunity in long-lived species for population persistence.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

CNRS Ecology Evolution SEE-Life program for long term monitoring

Ceva Wildlife Research Fund, CWR1

Agence Nationale de la Recherche, https://ror.org/00rbzpz17, ECOPATHS (ANR-21-CE35-0016), WILDFLU (ANR-25-CE35-0691)

Ailes Marines

Observatoire de Recherche Montpelliérain de l'Environnement OREME, https://ror.org/00cesps27, SO ECOPOP

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.08.25.745523v1

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Evaluating the #impact of #antiviral post-exposure #prophylaxis for health-care workers during #orthoebolavirus outbreaks: a modelling study

 

Summary

Background

Orthoebolavirus outbreaks place health-care workers (HCWs) at substantial risk, and HCW illness or death can weaken response capacity. The 2026 Bundibugyo virus outbreak in DR Congo highlights the need for deployable countermeasures when species-specific vaccines are unavailable. With candidate antivirals under evaluation, we aimed to estimate the impact of HCW-targeted antiviral post-exposure prophylaxis (PEP) across different readiness, disruption, and allocation scenarios.

Methods

We adapted a previously published stochastic branching-process model of orthoebolavirus transmission, representing health care, community, and funeral transmission; time-varying non-pharmaceutical interventions; and HCW-targeted PEP. The model was calibrated to two historical outbreaks using sequential approximate Bayesian computation: the 2013–16 west Africa epidemic, to define a high-burden, reasonable worst-case scenario archetype (west Africa-like archetype); and the 2018–20 North Kivu and Ituri outbreak in eastern DR Congo, to define an archetype with longer transmission under conflict-related response disruption (DR Congo-like archetype). The primary outcome was HCW deaths averted. For both archetypes, we simulated three antiviral deployment readiness scenarios (scenario 1: 100% coverage on day 0; scenario 2: scaled up to 80% coverage over 180 days; and scenario 3: scaled up to 50% coverage over 1 year) and compared their impact on HCW deaths with a scenario of no antiviral. For the DR Congo-like archetype only, we simulated four disruption scenarios: no antiviral PEP, ideal delivery (100% coverage and no dosing delay), delayed dosing with coverage preserved, and delayed dosing with delayed coverage. As a secondary outcome, we assessed number of PEP doses required per HCW death averted under different allocation scenarios.

Findings

At baseline (no antiviral PEP), cumulative HCW deaths reached a median of 553 (IQR 208–983) in the west Africa-like archetype by week 60, compared with 61 (19–125) in the DR Congo-like archetype by week 80. Assuming 80% efficacy and 80% coverage with antiviral PEP in the same timeframe in a central analysis, cumulative HCW deaths fell to 200 (68–349; equivalent reduction of 64% [63–66] relative to baseline) in the west Africa-like archetype and 22 (10–44; equivalent reduction of 64% [60–68]) in the DR Congo-like archetype. Under different scenarios of deployment readiness at 80% antiviral efficacy, the median reduction in HCW deaths compared with no PEP was 80% (95% CrI 79–81) in the west Africa-like archetype and 80% (76–84) in the DR Congo-like archetype for scenario 1; 60% (57–62) and 52% (41–58), respectively, for scenario 2; and 19% (16–22) and 22% (7–29), respectively, for scenario 3. In the DR Congo-like operational disruption analyses, an ideal scenario (PEP delivered at 100% coverage without a delay after exposure) averted 83% (79–87) of HCW deaths compared with no antiviral; maintaining 100% coverage but introducing delayed dosing (1–5 days post-exposure) reduced this finding to 50% (40–55) compared with no antiviral. Delayed coverage and dosing resulted in only 35% (25–47) of the ideal scenario impact. At 80% antiviral efficacy with same-day dosing, targeted allocation of recognised high-risk exposures (such as personal protective equipment breaches or direct body-fluid contact) required 44 doses (95% Crl 43–44) per HCW death averted versus 109 doses (85–161) with broad allocation.

Interpretation

HCW-targeted antiviral PEP could substantially reduce HCW deaths during orthoebolavirus outbreaks if efficacious antivirals can be delivered rapidly and high operational coverage is maintained. Comparisons of antiviral use cases and alternative response investments are needed to determine how resources can best support outbreak response.

Funding

Gilead Sciences, UK National Institute for Health and Care Research, Oxford Martin School, Miller Institute, EU Global Health EDCTP3, and Coalition for Epidemic Preparedness Innovations.

Translations

For the French and Swahili translations of the abstract see Supplementary Materials section.

Source: 

Link: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(26)00437-8/fulltext?rss=yes

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