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#USA, #Wastewater Data for Avian #Influenza A(#H5) (CDC, June 6 '25)

  {Excerpt} Time Period: May 25, 2025 - May 31, 2025 - H5 Detection :  10 sites ( 2.5% ) - No Detection :  389 sites ( 97.5% ) - No samples in last week :  52 sites (...) Source: US Centers for Disease Control and Prevention,  https://www.cdc.gov/nwss/rv/wwd-h5.html ____

#Antigenic and #virological characteristics of #SARS-CoV-2 #variants BA.3.2, #XFG, and #NB181

{Excerpt} The SARS-CoV-2 saltation variant BA.3.2 , harbouring over 50 mutations relative to its ancestral BA.3 lineage , has recently drawn global attention (figure A). Notably, BA.3.2 exhibits 44 mutations distinct from the currently dominant LP.8.1/LP.8.1.1 variant (appendix p 4), raising speculation about its potential to drive an outbreak similar to BA.2.86 /JN.1, particularly following its first detection outside South Africa in the Netherlands on April 2, 2025.1–5 A critical evaluation of its antigenic profile and infectivity is essential to establish its likelihood of prevailing. (...) Source: The Lancet Infectious Diseases,  https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00308-1/fulltext?rss=yes ____

#Serological insights into #MERS-CoV dynamics of #antibody responses during acute and convalescent phases and their clinical relevance for #diagnostics and immunity

Abstract Introduction Middle East respiratory syndrome (MERS) is a zoonotic viral respiratory disease caused by the Middle East respiratory syndrome coronavirus (MERS-CoV), associated with severe clinical outcomes and high mortality. Objectives Our study examined the kinetics of anti-MERS-CoV IgM and IgG antibodies during the acute and convalescent phases of infection, focusing on their correlations with clinical variables such as age and viral load. Methods Serum samples were collected from PCR-confirmed MERS-CoV patients (n = 23) during both phases and compared to healthy controls (n = 23) using validated ELISA-based assays. Results IgM levels peaked in the acute phase and declined significantly in the convalescent phase , while IgG levels were sustained and markedly higher during recovery . Correlation analyses revealed positive relationships between antibody levels and patient age (acute IgM: r = 0.56, p < 0.01; convalescent IgG: r = 0.59, p < 0.01) and viral loads (acute IgM...

Immediate #PB2-E627K amino acid #substitution after single #infection of highly pathogenic avian #influenza #H5N1 clade 2.3.4.4b in mice

Abstract The highly pathogenic avian influenza virus (HPAIV) H5N1 clade 2.3.4.4b has rapidly disseminated globally , with mammalian infections reported in multiple species. Recent evidence of mammal-to-mammal transmission has heightened concerns about the virus’s potential adaptation to mammals . The polymerase basic 2 (PB2) protein E627K mutation appears to be of key importance for mammalian adaptation. We isolated an HPAI H5N1 clade 2.3.4.4b virus from wild birds in Korea with 96% E and 4% K at amino acid position 627 of PB2 . To investigate the genomic characteristics of this clade regarding mammalian adaptation, we studied the replication and transmission of the H5N1 virus in mice. Two experiments with different challenge-to-contact ratios were conducted to assess transmission dynamics and mutation development . In experiment 1, a 4:1 challenge-to-contact ratio resulted in 100% transmission among direct-contact mice , with all mice succumbing to the infection. In experiment 2, a 1:...

Chimeric #hemagglutinin and #M2 #mRNA #vaccine for broad #influenza subtype protection

Abstract Since multiple and unpredicted influenza viruses cause seasonal epidemics and even high-risk pandemics , developing a universal influenza vaccine is essential to provide broad protection against various influenza subtypes. Combined with the mRNA lipid nanoparticle-encapsulated (mRNA-LNP) vaccine platform and chimeric immunogen strategy , we developed a novel cocktail mRNA vaccine encoding chimeric HAs (cH5/1-BV, cH7/3) and intact M2 (termed Fluaxe), which confers broad protection against major circulating IAVs and IBVs , as well as highly pathogenic avian influenza . Two-dose intramuscular immunization of Fluaxe in mice elicited cross-reactive neutralizing antibodies , T cell responses, and long-lived immunity, resulting in robust protection against multiple lethal influenza virus infections and severe acute lung injuries . In particular, intramuscular administration stimulated systemic immunity together with a prominent lung tropism of memory cells . Moreover, Fluaxe immuniza...

Genetic diversity of #H9N2 avian #influenza viruses in #poultry across #China and implications for #zoonotic transmission

Abstract Nationwide surveillance of avian influenza viruses (AIVs) in live poultry markets across China has occurred since 2014, providing a resource for AIV prevalence and genetic diversity studies . Here we report that 3,237 of 18,425 samples from poultry were AIV positive (17.57%) between 2019 and 2023, with H9N2 being the dominant subtype . We developed an automated phylogeny-based nomenclature system to classify genetic clades of the dominant H9N2 lineage, the BJ94 lineage. Using this model, we found that ten haemagglutinin (HA) sub-subclades cocirculated in poultry and showed antigenic variation. In addition, 99.46% and 96.17% of H9N2 AIVs in 2021–2023 possessed human-receptor binding-related HA-L226 and human MxA-resistance-related NP-N52 mutations , respectively. H9N2 strains with these two mutations preferred human-type receptors and increased replication in human cells in vitro, regardless of the presence of PB2-V/K/E627. Moreover, H9N2 AIVs containing HA-L226, PB2-V/K627 and...

No evidence of immune #exhaustion after repeated #SARS-CoV-2 #vaccination in vulnerable and healthy populations

Abstract Frequent SARS-CoV-2 vaccination in vulnerable populations has raised concerns that this may contribute to T cell exhaustion , which could negatively affect the quality of immune protection. Herein, we examined the impact of repeated SARS-CoV-2 vaccination on T cell phenotypic and functional exhaustion in frail older adults in long-term care (n = 23), individuals on immunosuppressive drugs (n = 10), and healthy adults (n = 43), in Canada . Spike-specific CD4+ and CD8+ T cell levels did not decline in any cohort following repeated SARS-CoV-2 vaccination, nor did the expression of exhaustion markers on spike-specific or total T cells increase. T cell production of multiple cytokines (i.e. polyfunctionality) in response to the spike protein of SARS-CoV-2 did not decline in any cohort following repeated vaccination. None of the cohorts displayed elevated levels of terminally differentiated T cells following multiple SARS-CoV-2 vaccinations. Thus, repeated SARS-CoV-2 vaccination was...

qRT-PCR #Detection of Inactivated #H5 Avian #Influenza Virus in Raw #Milk Samples by Miniaturized Instruments Designed for On-Site Testing

Abstract Highly pathogenic avian influenza virus (HPAIV) of H5 and H7 subtypes has emerged as one of the most important zoonotic pathogens in the 21st century with significant economic consequences. The recent outbreak of H5N1 avian influenza (AI) in dairy cattle highlighted the importance of early detection in managing and mitigating HPAIV outbreaks. A successful high-speed diagnostic response requires rapid site and specimen access, minimal time for test protocols, and prompt communication of the diagnostic results to government officials. A new diagnostic paradigm that consists of miniaturized extractor and qPCR instruments (EZextractor and EZcycler MiniQ), designed for mobile, on-site testing has been compared with a platform of benchtop instruments (QIAGEN RNeasy and QuantStudio 5) for detecting inactivated H5 avian influenza virus (AIV) spiked in raw milk samples. Two sets of experiments were performed: 1) 15 raw milk samples, obtained from 15 different farms, diluted with phosph...

#Corynebacterium diphtheriae #Outbreak in #Migrant Populations in #Europe

Abstract Background A surge of cases of Corynebacterium diphtheriae infection was observed in reception centers for migrants in Europe beginning in the summer of 2022. Most of the cases were cutaneous , although some respiratory cases as well as one death were reported. A pan-European consortium was created to assess the clinical, epidemiologic, and microbiologic features of this outbreak. Methods We assessed cases of toxigenic C. diphtheriae infection that were reported in 10 European countries from January through November 2022. Data regarding countries of origin and transit routes were obtained from interviews with the patients. Whole-genome sequencing and antimicrobial-susceptibility testing were performed on bacterial isolates that were obtained from the patients. The phylogenetic relationships of the isolates and their antimicrobial-resistance genes were evaluated. Results A total of 363 toxigenic C. diphtheriae isolates were identified among 362 patients during the study period....

The #hemagglutinin proteins of clades 1 and 2.3.4.4b #H5N1 #HPAI viruses exhibit comparable attachment patterns to #avian and #mammalian tissues

Abstract The global spread of the A/goose/Guangdong/1/96-lineage H5N1 highly pathogenic avian influenza (HPAI) viruses is accompanied by an expanded host range and the establishment of sustained viral transmission among dairy cattle . To evaluate if the evolving H5N1 viruses have changed tissue tropism over time, we compared the binding patterns of recombinant hemagglutinin (HA) proteins derived from clade 1 (A/Vietnam/1203/04, H5VN) and circulating clade 2.3.4.4b viruses detected from a wild bird (A/Eurasian Teal/Hong Kong/AFCD-HKU-23-14009-01020/2023, H5HK) and dairy cattle (A/bovine/Ohio/B24OSU-439/2024, H5OH). The HA protein of A(H1N1)pdm09 virus was included for comparison. Using bio-layer interferometry, H1 protein preferentially bound to the 2,6-linked sialoside 6'SLNLN while H5 proteins preferentially bound to the 2,3-linked sialoside 3'SLN. H5OH showed higher binding affinity to 3'SLN than H5HK and H5VN. The attachment pattern of H1 and H5 proteins to the respirato...

#SARS-CoV-2 infection #enhancement by #amphotericin B: implications for disease management

ABSTRACT Severe coronavirus disease 2019 (COVID-19) patients who require hospitalization are at high risk of invasive pulmonary mucormycosis . Amphotericin B (AmB), which is the first-line therapy for invasive pulmonary mucormycosis, has been shown to promote or inhibit replication of a spectrum of viruses. In this study, we first predicted that AmB and nystatin had strong interactions with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins using in silico screening, indicative of drugs with potential therapeutic activity against this virus. Subsequently, we investigated the impact of AmB, nystatin, natamycin, fluconazole, and caspofungin on SARS-CoV-2 infection and replication in vitro. Results showed that AmB and nystatin actually increased SARS-CoV-2 replication in Vero E6, Calu-3, and Huh7 cells . At optimal concentrations, AmB and nystatin increase SARS-CoV-2 replication by up to 100- and 10-fold in Vero E6 and Calu-3 cells, respectively. The other antifungals t...

Quantifying the #zoonotic #risk profile of European #influenza A viruses in #swine from 2010 to 2020 inclusive

ABSTRACT H1 and H3 influenza A viruses (IAVs) circulating in European pigs are markedly distinct from those circulating in other global swine populations . These viruses exhibit significant genetic diversity , further expanded by periodic interspecies transmission of IAVs from humans into pigs , followed by sustained circulation. Several zoonotic IAV infections in humans in Europe have been associated with the 1C lineage of H1 IAVs . Given the predominance of H1 detections in pigs and their zoonotic potential, we quantified antigenic evolution of H1 viruses in European pigs using ferret and pig models and assessed diversity relative to swine IAV vaccine strains. Ferret and swine antisera comparisons revealed no significant differences in antibody responses . Viruses of the 1A.3.3.2 clade exhibited reduced cross-reactivity to human seasonal vaccine strains from 2009. Viruses of the 1B.1.2.2 clade showed no cross-reactivity to the 1978 human seasonal influenza viruses nor to candidate va...

A replicating recombinant vesicular stomatitis virus #model for dairy #cattle #H5N1 #influenza virus #glycoprotein #evolution

ABSTRACT A panzootic of highly pathogenic avian influenza (HPAI) H5N1 viruses from clade 2.3.4.4b has triggered a multistate outbreak in US dairy cattle and an unknown number of human infections . HPAI viruses are handled in specialized biocontainment facilities. Ethical considerations limit certain evolution experiments aimed at assessing viral resistance to potential therapeutics. We have developed a replicating recombinant vesicular stomatitis virus (rVSV) where we replaced its glycoprotein with the hemagglutinin (HA) and neuraminidase (NA) genes of a 2.3.4.4b H5N1 virus (rVSV-H5N1dc2024), which enables these experiments to be performed under standard biosafety considerations. This virus grows to high titers and encodes a fluorescent reporter to track infection. We demonstrate the utility of rVSV-H5N1dc2024 in neutralization experiments, the evaluation of antibody escape, and the characterization of resistance mutations to NA inhibitors. rVSV-H5N1dc2024 or similar viruses may accele...

#Phage-induced #protection against lethal #bacterial #reinfection

Significance In 2021, antimicrobial-resistant bacteria were responsible for 1.14 million deaths and associated with 4.71 million deaths globally. Patients who experience sepsis often face a higher risk of reinfections and hospital readmissions . To combat this crisis, bacteriophages —viruses that infect and kill bacteria—are regaining interest as a potential solution. Here, we show that mice infected with extraintestinal pathogenic Escherichia coli and treated with phage HP3 not only recover from the initial infection but also gain protection against a secondary challenge with the same bacterial strain. The protective effect is dependent on the bacteriolytic action of the phage. These findings shift phages from being solely therapeutic antimicrobials to dual-action immunotherapeutics capable of both clearing and preventing bacterial infections. Abstract Bacteriophages, or phages, are viruses that target and infect bacteria. Due to a worldwide rise in antimicrobial resistance (AMR), pha...

#Neuroinvasive #Oropouche virus in a patient with #HIV from extra-Amazonian #Brazil

{Excerpt} A novel reassortant Oropouche virus (OROV) lineage (with medium [M], large [L], and small [S] RNA segments : M1L2S2) has driven Brazil's largest and most geographically widespread OROV epidemic , expanding beyond the endemic Amazon basin to establish local transmission across multiple Brazilian states and other previously unaffected Latin American countries . The rapid spread of this lineage underscores its evolutionary potential and reinforces its significance as a public health threat .1 Similar to chikungunya and Zika viruses, expanding arboviruses can exhibit unexpected clinical and epidemiological shifts , including vertical transmissions , neuroinvasive effects, and potentially fatal outcomes.2–4 Although OROV typically causes self-limited febrile illness, accumulating clinical and experimental evidence suggests neurotropic potential .5 This Correspondence describes the first confirmed case of neuroinvasive OROV infection caused by the emergent M1L2S2 lineage in ext...

Persistence of #SARS-CoV-2 #Alpha #Variant in White-Tailed #Deer, #Ohio, USA

Abstract Free-ranging white-tailed deer (WTD) are highly susceptible to the SARS-CoV-2 virus . Through an opportunistic sampling of WTD in northeast Ohio, USA , during January–March 2023 , we identified 6 SARS-CoV-2 lineages from 36 sequences using the pangolin lineages tool, including the B.1.1.7 lineage (Alpha variant) and BQ.1.1, BQ.1.1.63, BQ.1.1.67, BQ.1.23, and XBB.1.5.35 lineages ( Omicron variant ). The Alpha variant, introduced by a single human-to-deer transmission event , was detected in 5 WTD in January 2023, more than 1 year after the most recent detection of the Alpha variant in humans in Ohio (August 2021). A genetically similar B.1.1.7 lineage virus from WTD in a nearby county in Pennsylvania was positioned with our Ohio deer transmission cluster, suggesting deer-to-deer transmission . The persistence of the Alpha variant in WTD in Ohio warrants continued surveillance to monitor if WTD can become a reservoir for displaced SARS-CoV-2 variants. Source: US Centers for Dise...

#Risk #evaluation of newly emerging #flu viruses based on genomic #sequences and AI

Abstract The recent resurgence of highly pathogenic avian influenza H5N1 viruses in North America and Europe has heightened global concerns regarding potential influenza pandemics. Despite significant progress in the surveillance and prevention of emerging influenza viruses, effective tools for rapid and accurate risk assessment remain limited. Here, we present FluRisk , an innovative computational framework that integrates viral genomic data with artificial intelligence (AI) to enable rapid and comprehensive risk evaluation of emerging influenza strains. FluRisk incorporates a curated database of over 1,000 experimentally validated molecular markers linked to key viral phenotypes , including mammalian adaptation, mammalian virulence, mammalian transmission, human receptor-binding preference , and antiviral drug resistance . Leveraging these markers, we developed three state-of-the-art machine learning models to predict human adaptation, mammalian virulence, and human receptor-binding ...

#Influenza at the #human - #animal #interface - #Summary and #risk #assessment, from 23 April to 27 May 2025 (#WHO, June 3 '25)

  New human cases {2}:  -- From 23 April to 27 May 2025, based on reporting date, the detection of influenza A( H5N1 ) in three humans, the detection of influenza A( H9N2 ) virus in eight humans and the detection of influenza A( H10N3 ) in one human were reported officially.  -- Circulation of influenza viruses with zoonotic potential in animals:  - High pathogenicity avian influenza (HPAI) outbreaks in poultry and non-poultry animals continue to be reported to the World Organisation for Animal Health (WOAH).{3}  - The Food and Agriculture Organization of the United Nations (FAO) also provides a global update on avian influenza viruses with pandemic potential.{4}  -- Risk assessment {5}:  - Sustained human to human transmission has not been reported in these events. Based on information available at the time of the risk assessment , the overall public health risk from currently known influenza viruses circulating at the human-animal interface has not c...

Single-Cell #Analysis of Host Responses in #Bovine #Milk Somatic Cells (bMSCs) Following #HPAIV Bovine #H5N1 #Influenza Exposure

Abstract The 2024 outbreak of highly pathogenic avian influenza virus (HPAIV) H5N1 in U.S. dairy cattle presented an unprecedented scenario where the virus infected bovine mammary glands and was detected in milk , raising serious concerns for public health and the dairy industry. Unlike previously described subclinical influenza A virus (IAV) infections in cattle, H5N1 infection induced severe clinical symptoms , including respiratory distress, mastitis, and abnormal milk production . To understand the host immune responses and changes, particularly in the mammary gland, we performed single-cell RNA sequencing analysis on bovine milk somatic cells (bMSCs) in vitro exposed to an H5N1 isolate from an infected dairy farm. We identified ten distinct cell clusters and observed a shift toward type-2 immune responses , characterized by T cells expressing IL13 and GATA3 , and three different subtypes of epithelial cells based on the expression of genes associated with milk production. Our stud...

Recurrent #MERS-CoV #Transmission in #Saudi Arabia– Renewed Lessons in #Healthcare #Preparedness and Surveillance

{Excerpt} The World Health Organization (WHO) had recently announced on May 12 , 2025, the reporting of nine new laboratory-confirmed cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Saudi Arabia [1]. This announcement is a sobering reminder that while the global community remains focused on emergent threats like avian influenza or post-pandemic resilience, endemic zoonotic diseases like MERS-CoV may continue to circulate, evolve, and exploit gaps in infection prevention. (...) Source: Journal of Epidemiology and Global Health,  https://link.springer.com/article/10.1007/s44197-025-00426-6 ____