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Decoding non-human #mammalian adaptive #signatures of 2.3.4.4b #H5N1 to assess its #human adaptive potential

ABSTRACT The 2.3.4.4b clade highly pathogenic avian influenza H5N1 infected diverse non-human mammalian species , gained mammal-to-mammal transmission potential , and caused sporadic human infections . However, whether non-human mammals enable the human adaptation of 2.3.4.4b H5N1 to establish human infections is unclear. Gain-of-function research restrictions may hinder the assessment of 2.3.4.4b H5N1 human adaptations. Here, we tracked the evolution of 2.3.4.4b H5N1 that infected non-human mammals and evaluated their ability to gain human adaptations. The non-human mammal 2.3.4.4b H5N1 partly acquired classical human-adapting mutations , which are identical to the residues of H1N1pdm09 and seasonal human H3N2 viruses, while showing a few species-specific adaptations that might be potential barriers for successful human infections. The polymerase complex proteins , PA and PB2, acquired human adaptations in non-human mammals, with fox-infected viruses showing more positive selection in...

#COVID19 #pandemic resulted in more metastatic #breast #cancer cases at #diagnosis

Abstract The study aimed to assess the impact of the COVID-19 pandemic on breast cancer diagnosis, tumor characteristics, and staging in an Eastern-European country . This retrospective study included 11,635 breast cancer patients and clients presenting between March 2019 and March 2022. Patients were categorized into pre-pandemic, pandemic, and post-pandemic groups . Data included age, sex, pathology, tumor characteristics (histologic type, grade, ER/PR/HER2 status), and TNM staging . Statistical analysis compared these parameters across the three-time intervals. During the pandemic, breast cancer diagnosis decreased significantly compared to the pre-pandemic period (9.1% vs. 13.17%, p < 0.001) but increased post-pandemic (11%, p = 0.013). Invasive ductal carcinoma of non-special type (IDC-NST) was predominant in all three-time periods. Aggressive tumors (Nottingham grade 3, ER negative) increased during the pandemic and post-pandemic times . Molecular subtypes showed variations ac...

The Abbey in the Oakwood, Caspar David Friedrich (1809 - 1810)

  Public Domain. Source: WikiArt,  https://www.wikiart.org/en/caspar-david-friedrich/the-abbey-in-the-oakwood _____

History of Mass Transportation: The DB VT 11.5 Autotrain

  By Benedikt Dohmen (User:Benedictus), Archiv-Nr. 92/39 - Own work, CC BY-SA 3.0,  https://commons.wikimedia.org/w/index.php?curid=496875 Source: Wikipedia,  https://en.wikipedia.org/wiki/DB_Class_VT_11.5 ____

Companion #animals and #H5N1 highly pathogenic avian #influenza: cause for #concern?

Abstract The first known human infection with a highly pathogenic H5N1 influenza A virus appeared in China in 1997 . Between 2003 and 2017, the WHO documented an additional 862 human cases, mainly from southeast Asia and Egypt , with a mean annual case fatality rate of 56%. By 2006, the susceptibility of cats to severe respiratory and neurologic disease became apparent. Scientists raised concerns regarding the potential for domestic cats to transmit novel pathogenic strains to humans. But after 2006, reports of new H5N1 infections in companion animals dwindled, and human cases fell after 2016. In 2021, H5N1 clade 2.3.4.4b viruses suddenly appeared in Europe and spread rapidly to the Americas , wreaking havoc on wildlife and crippling the poultry and dairy industries . Between 2022 and 2025, dozens of domestic cats died , most often following raw food consumption . Unease regarding the transmission potential of pets resurfaced. Although most human infections in the Americas were mild an...

A multivalent #mRNA #vaccine elicits robust immune responses and confers #protection in a murine #model of #monkeypox virus infection

Abstract Monkeypox virus (MPXV) has re-emerged globally since May 2022, posing a significant public health threat . To address this, we develop two multivalent mRNA vaccine candidates —AAL, encoding three MPXV antigens, and AALI, which combines AAL with an immune-enhancing IFN-α protein. Both vaccines are delivered via mannose-modified lipid nanoparticles to target dendritic cells . Here we show that these vaccines elicit strong antibody responses against vaccinia virus and multiple MPXV clades , induce robust memory B-cell and T-cell responses, and promote dendritic cell maturation . In mouse challenge models , both vaccines provide protection against clade IIb MPXV and vaccinia virus , significantly reducing viral loads and preventing lung damage. Immune profiling reveals enhanced B- and T-cell receptor diversity and distinct CDR3 motifs post-vaccination. These findings demonstrate the potential of using mRNA-based multivalent vaccines as an effective strategy for preventing mpox and...

#Coronavirus Disease Research #References (by AMEDEO, August 9 '25)

  Ann Intern Med CONLY J Expression of Concern: Medical Masks Versus N95 Respirators for Preventing COVID-19 Among Health Care Workers. Ann Intern Med. 2025 Aug 5. doi: 10.7326/ANNALS-25-03203. PubMed          BADUASHVILI A, Radonovich L, Leslie L, Pease S, et al Engineering Infection Controls to Reduce Indoor Transmission of Respiratory Infections : A Scoping Review. Ann Intern Med. 2025 Aug 5. doi: 10.7326/ANNALS-25-00577. PubMed           Abstract available Antiviral Res YAO G, Shi X, Jiang H, Duan A, et al Design, synthesis, and biological evaluation of novel 6-aminoalkyl- and 7-heteroaryl substituted 7-deazapurine nucleoside analogs against SARS-CoV-2 Replication. Antiviral Res. 2025 Aug 1:106246. doi: 10.1016/j.antiviral.2025.106246. PubMed           Abstract available Clin Infect Dis BHIMRAJ A, Falck-Ytter Y, Baden LR, Bedimo R, et al 2025 Clinical Practice Guid...

#Influenza and Other Respiratory Viruses Research #References (by AMEDEO, August 9 '25)

  Antimicrob Agents Chemother HARFOOT R, Lawley B, Hernandez LC, Kuang J, et al Synthetic host defense peptide inhibits SARS-CoV-2 replication in vitro. Antimicrob Agents Chemother. 2025;69:e0170024. PubMed           Abstract available TATE M, Illingworth CJR, MacGregor G, Cunningham L, et al Clinical effectiveness, safety, and viral mutagenicity of oral favipiravir for COVID-19: results from a community-based, open-label, randomized Phase III trial. Antimicrob Agents Chemother. 2025;69:e0005425. PubMed           Abstract available ZHOU Y, Meng X, Li J, Zeng G, et al Safety, tolerability, and pharmacokinetics of anti-SARS-CoV-2 monoclonal antibody SA55 injection in healthy participants. Antimicrob Agents Chemother. 2025;69:e0056825. PubMed           Abstract available GOMI S, Price E, Burgoyne H, Faozia S, et al Omadacycline exhibits anti-inflammatory properties a...

#Sialic Acid #Receptors in #Human Mammary Tissue: Implications for #Infection with Novel #Influenza Strains

  Abstract Importance :  Highly pathogenic avian influenza (HPAI) A H5N1 has been recognized for nearly three decades as a threat to avian species and as a virus with pandemic potential if spillover into human populations occurs. Recently the virus has evolved capacity to infect many mammalian species , including dairy cattle , increasing the risk for human exposure and the pandemic threat. Sialic acids (SA) serve as binding sites for influenza viruses. The distribution of SA determines infectivity of specific influenza viruses across species and tissue tropism . Hemagglutinin (HA) of human and swine adapted influenza viruses bind primarily to SA with α2,6-galactose linkages and avian influenza viruses preferentially bind to SA with α2,3-galactose linkages . Recently, the bovine udder was found to contain SA with α2,3 linkages which allow the H5N1 virus to bind to bovine udder epithelium and to infect milk. The distribution of SA receptors in the human mammary gland is unknown...

Subtype-specific neutralizing #antibodies promote #antigenic #shift during #influenza virus co-infection

  Abstract Reassortment between different influenza strains occurs when they co-infect the same host cell . The emergence of a reassortant virus depends on both its intrinsic fitness and extrinsic factors , including pre-existing humoral immunity . The generation of pandemic strains , such as H2N2 and H3N2 , and zoonotic influenza A viruses, like H5N6, H5N8, and H7N9 , in birds is suggested to be the result of extensive selection by pre-existing antibodies . To further explore the role of humoral immunity in reassortment , we generated two divergent fluorescent protein-expressing viruses and used strain-specific and cross-reactive monoclonal antibodies (mAbs) to assess the impact of cross-immunity on reassortment. Our results indicate that all mAbs altered the genotypic diversity and significantly reduced the release of progeny virions in co-infected cells both in vitro and in vivo. Moreover, antibody transfer studies in mice revealed protection from challenge with divergent pathog...

#Cytokine Regulation of #Human #Antibody Responses to #Influenza #Vaccines

  Abstract Vaccine responses vary widely in human studies. Here we pooled data measuring 66 cytokines from 4 different inactivated influenza vaccine (IIV) cohorts over 5 seasons (N=581) and identified a significant correlation between baseline/day 0 serum IL-18 and IFN-β concentrations and the antibody response on day 28. We investigated this further in human tonsil and spleen organoids , and found that several cytokines, including multiple Type I IFNs (IFN-β and others), IL-21, IL-12, IL-10, but not IL-18 or its downstream Type II IFN (IFN-β), could adjuvant the IIV vaccine to enhance the antibody response . The live attenuated influenza vaccine (LAIV) induced a stronger antibody response than the inactivated one in organoids. Adding a single cytokine, IFN-β, recapitulated most of the live vaccine-specific cytokine activation program and increased the antibody response of the inactivated vaccine to that of the live vaccine. Thus, the human vaccinees and the organoid data showed th...

History of Mass Transportation: The FS Ale 501 Electric Multiple Unit

  De user:axpde - Opera propia, GFDL,  https://commons.wikimedia.org/w/index.php?curid=11625891 Source: Wikipedia,  https://it.wikipedia.org/wiki/Minuetto_(treno) ____

A versatile #H5N1-VSV #platform for safe #influenza virus #research applications

  ABSTRACT The H5N1 strain of influenza A virus (IAV) continues to cause severe infections in a range of avian and mammalian species , including sporadic but concerning cases in humans. There is growing concern that circulating H5N1 strains could lead to widespread human outbreaks . Research with highly pathogenic H5N1 viruses is restricted to Biosafety Level 3 (BSL-3) laboratories. Vesicular stomatitis virus (VSV)-based vaccine vectors expressing heterologous viral proteins from Ebola, SARS-CoV-2, Lassa virus, etc., have previously been shown to be safe and effective in animal models and human clinical trials . Here, we report the development of a recombinant VSV expressing the hemagglutinin (HA) and neuraminidase (NA) genes of H5N1 IAV (H5N1-VSV), which serves as a versatile platform to study various aspects of H5N1 IAV biology. H5N1-VSV replicated robustly to titers comparable to those of the full H5N1 virus in multiple cell lines. In mice , H5N1-VSV vaccination was safe, elicit...

#Inflammatory, transcriptomic, and #cell fate responses underlying the #mammalian #transmission of avian #influenza viruses

  ABSTRACT Airborne transmissibility of avian influenza viruses (AIVs) in humans is considered an essential component of their pandemic risk . Although several viral factors regulating airborne transmission (AT) have been delineated, it is not known what, if any, responses at the respiratory epithelia are determinants of AIV AT. Using responses in the ferret nasal epithelium to a panel of H1N1 AIVs, we describe host responses that segregate with AT phenotypes . AIV infection upregulated interferon alpha and gamma responses and IL-6 JAK-STAT signaling and downregulated oxidative phosphorylation . Single-cell transcriptomics revealed that cellular genotoxic stress and NF-kB, interferon, and cell fate pathways differentiated host responses to AIVs with different transmissibilities. These responses culminated in greater AIV antigen-containing exudate and debris in the respiratory spaces of the nasal epithelium of ferrets inoculated with AT AIVs. More abundant CMPK2, SP100, and CXCL10 t...

#USA, #Wastewater Data for Avian #Influenza #H5 (#CDC, August 8 '25)

  {Summary} Time Period: July 27, 2025 - August 02, 2025 -- H5 Detection :  4 sites ( 0.9% ) -- No Detection :  430 sites (99.1%) -- No samples in last week :  24 sites (...) Source: US Centers for Disease Control and Prevention,  https://www.cdc.gov/nwss/rv/wwd-h5.html ____

#India - High pathogenicity avian #influenza #H5N1 viruses (#poultry) (Inf. with) - Immediate notification

  Two Poultry Farms in the Odisha State. Source: WOAH,  https://wahis.woah.org/#/in-review/6694 ____

Post-exposure #prophylaxis regimen of #rabies monoclonal #antibody and #vaccine in category 3 potential exposure patients ...

  Summary Background Rabies is almost invariably fatal . A rabies monoclonal antibody (RmAb) was approved in India in 2016 for passive prophylaxis. This post-marketing study aimed to evaluate the long-term safety, immunogenicity, and efficacy of a post-exposure prophylaxis (PEP) regimen containing RmAb. Methods This phase 4, open-label, randomised, active-controlled study was conducted at 15 tertiary care hospitals in India . Patients aged 2 years or older with WHO category 3 rabies exposure by a suspected rabid animal were eligible if the exposure occurred less than 72 h before enrolment, or less than 24 h before enrolment for exposures to the face, neck, hand, or fingers. Participants were randomly assigned (3:1) to receive either RmAb (Rabishield; Serum Institute of India, Pune, India) plus a purified Vero cell rabies vaccine (PVRV; Rabivax-S) or equine rabies immunoglobulin (ERIG; Equirab) plus PVRV as PEP. In each treatment group, patients were further randomly assigned (1:1) ...

#MERS-related #coronavirus circulating in #pangolins exhibits strong fusogenicity in #human #cells and high sensitivity to fusion inhibitors

Highlights •  MjHKU4r-CoV-1 with high fusogenicity induces inflammatory responses in human cells •  6-HB structure determination unveils MjHKU4r-S-mediated membrane fusion mechanism •  MjHKU4r-CoV-1 HR2 peptides exhibit potent activity by targeting viral HR1 domain •  Stapled peptide MjHKU4r-HR2P10 shows potent and broad-spectrum anti-CoV activity Summary Unlike preceding MERS-related coronaviruses, the recently identified MjHKU4r-CoV-1 strain can directly infect human cells . Nonetheless, its potential pathogenic attributes and underlying molecular mechanisms remain unclear. We find that MjHKU4r-CoV-1 induces significant inflammation , including interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α), and exhibits pronounced fusogenicity mediated by its spike (S) protein, leading to extensive syncytium formation . This suggests the possibility that MjHKU4r-CoV-1 possesses strong pathogenic potential in humans . Further, we successfully reveal the molecular mechan...

Highly conserved #Betacoronavirus #sequences are broadly recognized by #human T cells

Highlights •  Conserved T cell epitope regions elicit strong CD4+ and CD8+ T cell responses in SARS2-exposed •  CTERs enhance cross-reactivity across multiple Betacoronaviruses •  Targeting non-spike proteins expands immune breadth and HLA coverage •  Removing low population coverage regions preserves cross-reactivity Summary The COVID-19 pandemic highlighted the critical need for vaccine strategies capable of addressing emerging viral threats . Betacoronaviruses, including severe acute respiratory syndrome coronavirus ( SARS-CoV ), Middle East respiratory syndrome ( MERS ), and SARS-CoV-2 , present significant pandemic risks due to their zoonotic potential and genetic diversity . T cell-mediated immunity has demonstrated durable responses and strong cross-reactivity, offering a promising avenue for achieving broad immunity within a viral family. In this study, we combined comprehensive epitope mapping with sequence conservation analyses to identify conserved T cell ...

#Italy, #WNV and #Usutu Virus Weekly #Surveillance #Bulletin No. 4, July 7 '25: 84 new confirmed cases (ISS)

{Summary} -- Since the last update (July 31), eighty-four new confirmed cases of human infection with West Nile Virus have been reported.  -- Since the start of epidemic season, there were 173 confirmed WNV cases, of which:  - 72 were West Nile Neuroinvasive Disease (WNND): (2 in Piedmont, 2 Lombardy, 4 Veneto, 1 Friuli-Venezia Giulia, 2 Emilia-Romagna, 37 Latium, 21 Campania, 1 Basilicata, 1 Sardegna),  - 14 were asymptomatic cases in blood donors ,  - 85 were West Nile Fever cases,  - 1 was an asymptomatic case  -- Among the confirmed cases, there were eleven fatalities : 1 in Piedmont, 4 Latium, 6 .  - The case-fatality rate among WNND cases is at 15% (during 2018 season it was 20%, whereas in 2024 it was 14%).  -- No new confirmed cases of Usutu Virus human infection have been reported during current surveillance week. (...) Source: High Institute of Health,  https://www.epicentro.iss.it/westnile/bollettino/Bollettino_WND_2025_04.pdf ____...