ETIDIOH - NEW

Abstract The continuous evolution and widespread dissemination of highly pathogenic avian influenza (HPAI) H5N1 viruses , particularly clade 2.3.4.4b, pose critical challenges to global pandemic preparedness . In this study, we assessed a low-dose inactivated split virus vaccine derived from clade 2.3.4.4b H5N1, formulated with an Alum/CpG adjuvant , using a preclinical mouse model . This vaccine induced potent humoral and cellular immune responses , generating high titers of cross-reactive antibodies targeting both hemagglutinin (HA) and neuraminidase (NA) glycoproteins across homologous and heterologous H5 clades. The Alum/CpG adjuvant enabled significant antigen dose-sparing while promoting a balanced Th1/Th2 immune profile . Functional analyses demonstrated strong virus neutralization , neuraminidase inhibition, and potent antibody-dependent cellular cytotoxicity activity . Additionally, the vaccine elicited robust antigen-specific CD4+ and CD8+ T cell responses and effectively con...

  ABSTRACT The mammary gland is an essential organ for milk production, providing essential immune and nutritional support to offspring and supplying dairy products for human consumption. In both humans and animals , the lactating mammary gland is susceptible to bacterial and viral infections , which can lead to mastitis and, in some cases, vertical transmission to offspring , with potential adverse effects on infant health. However, until recently, the role of respiratory viruses in mammary gland infection has been relatively understudied, particularly their ability to infect mammary epithelial cells and transmit through lactation. The recent emergence of highly pathogenic avian influenza H5N1 clade 2.3.4.4b in dairy cattle has demonstrated the virus’s capacity to replicate in the mammary gland, cause mastitis, and produce high viral loads in milk . This raises significant concerns about the potential for zoonotic transmission to humans and other animals in contact with infected d...

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...

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...

  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...

ABSTRACT Seasonal influenza causes 290,000–650,000 deaths annually, with vaccination efficacy ranging from 10 to 60%. The emergence of drug-resistant and highly pathogenic avian influenza viruses underscores the urgent need for novel protective strategies . Epidemiological observations have long suggested that certain vaccines, such as Bacillus Calmette-Guérin (BCG), can provide protection against diverse pathogens (S. Biering-Sørensen, P. Aaby, N. Lund, et al., Clin Infect Dis 65:1183–1190, 2017, https://doi.org/10.1093/cid/cix525 ; M.-L. Garly, C. L. Martins, C. Balé, et al., Vaccine 21:2782–2790, 2003, https://doi.org/10.1016/s0264-410x(03)00181-6 ; C. A. G. Timmermann, S. Biering‐Sørensen, P. Aaby, et al., Trop Med Int Health 20:1733–1744, 2015, https://doi.org/10.1111/tmi.12614 ). While the cellular and molecular mechanisms underlying such protection remain incompletely understood, emerging research offers critical insights into innate immune system modulation (B. Cirovic, L. C. J...

Abstract Transmission of highly pathogenic avian influenza from H5 clade 2.3.4.4b has expanded in recent years to infect large populations of birds and mammals , heightening the risk of a human pandemic . Influenza viruses adapted to transmission in birds and some other animals tend to have a less stable hemagglutinin (HA) than seasonal influenza viruses , enabling membrane fusion at comparatively high pH levels. Here, we combine five mutations within H5 HA that dramatically increase its melting temperature and promote stable closure of the HA trimer . Structural analysis by cryo-electron microscopy revealed that the stabilizing mutations create several new hydrophobic interactions , while maintaining local HA structure. We found that vaccinating mice with stabilized H5 HA immunogens resulted in higher hemagglutination inhibition and neutralization titers than non-stabilized comparators. Epitope mapping of vaccine-elicited polyclonal antibody responses using negative stain electron mic...

Abstract Highly Pathogenic Avian Influenza (HPAI) viruses, particularly H5N1 and H7N9, have long been considered potential pandemic threats , despite the absence of sustained human-to-human transmission. However, recent outbreaks in previously unaffected regions , such as Antarctica, suggest we may be shifting from theoretical risk to a more imminent threat . These viruses are no longer limited to avian populations. Their increasing appearance in mammals , including dairy cattle and domestic animals , raises the likelihood of viral reassortment and mutations that could trigger a human pandemic. If such a scenario unfolds, the world may face a crisis marked by high transmissibility and lethality, without effective vaccines readily available. Unlike the COVID-19 pandemic, when vaccines were rapidly developed despite inequities in access, the current influenza vaccine production model , largely reliant on slow, egg-based technologies, is insufficient for a fast-moving outbreak. While newe...

  Key points   -- At the present time , based on available information, FAO-WHO-WOAH assess the global public health risk of influenza A(H5) viruses to be low , while the risk of infection for occupationally or frequently exposed (e.g., with backyard poultry) persons is low to moderate depending on the risk mitigation and hygiene measures in place and the local avian influenza epidemiological situation.  -- Transmission between animals continues to occur and, to date, a growing yet still limited number of human infections are being reported. Although additional human infections associated with exposure to infected animals or contaminated environments are expected to occur, the overall public health impact of such infections at a global level , at the present time, is considered minor . The assessment could change if and when additional epidemiological or virological information becomes available.  -- This risk assessment from FAO, WHO and WOAH updates the assessment ...

Abstract With the recent rise in cases of highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b infection in humans and animals , there is an associated increase in the risk of human-to-human transmission . In this study, we characterize a recombinant A(H5N1) A/American Wigeon/South Carolina/22/000345-001/2021 (A/AW/SC/2021) clade 2.3.4.4b vaccine . Purified recombinant A/AW/SC/2021 HA trimers formulated with Matrix-M® adjuvant, saponin-cholesterol-phospholipid combination arranged in cage-like particles, are found to non-covalently anchor to the vertices of the Matrix-M and form A(H5N1) HA–Matrix-M nanoparticles (H5-MNPs). In naïve female mice , two intranasal (IN) or intramuscular (IM) doses of A/AW/SC/2021 H5-MNP vaccine induces robust antibody- and cell-mediated immune responses , including neutralizing antibodies against A(H5N1). In non-human primates (NHPs) primed with seasonal influenza vaccine , a single IM or IN dose of the A/AW/SC/2021 H5-MNP vaccine induces geometr...

ABSTRACT Effective vaccines are an important public health tool which may be needed to combat the emerging, highly pathogenic H5N1 avian influenza viruses currently circulating in cattle and poultry in the United States . While nucleic acid-based vaccines such as mRNA -lipid nanoparticles (LNPs) have several potential advantages during a viral epidemic compared to traditional seasonal influenza vaccines , their utility and efficacy against H5N1 viruses remain incompletely defined. Here, we developed novel DNA- and mRNA-LNP-based vaccines encoding both hemagglutinin (HA) and neuraminidase (NA) proteins from the human-isolated highly pathogenic avian influenza H5N1 strain, A/Texas/37/2024, in a single open reading frame. This dual-antigen expression approach elicited strong protective immune responses targeting both the HA and NA proteins and provided complete protection against lethal viral challenges in a murine model . The pre-clinical data described in this work suggest that these mu...

Abstract An increase in the number of human cases of influenza A/H5N1 infection in the US has raised concerns about the pandemic potential of the virus . Preexisting population immunity is a key determinant for risk assessment and pandemic potential for any virus. Antibody responses against the bovine A/H5N1 hemagglutinin (HA) and neuraminidase (NA) proteins were measured among a population of influenza-vaccinated or influenza-infected individuals . Modest titers of bovine A/H5N1 HA-binding antibodies and low to undetectable neutralizing antibody responses were detected in a cohort of 73 individuals . Conversely, bovine A/H5N1 NA binding and neuraminidase-inhibiting antibody responses were comparable to those against a human A/ H1N1 NA at baseline. Seasonal influenza vaccination failed to significantly increase antibody titers against both HA and NA glycoproteins of bovine A/H5N1. Recent infection with human A/H1N1 but not A/H3N2 viruses induced significant increases in bovine A/H5N1 n...

{Excerpt} 1. Background   A risk assessment exercise using the Tool for Influenza Pandemic Risk Assessment ( TIPRA ) was conducted for Clade 2.3.4.4b A(H5N1) genotype B3.13 virus in Aug – Oct 2024 .   From late 2023, unexplained illnesses were reported in dairy cattle across multiple states in the United States .  Following those events , detection of avian influenza A(H5N1) in dairy cattle from Texas was confirmed on 25 March 2024.  As of 9 December 2024 , the virus has been detected in 720 dairy cattle herds across 15 states, according to the United States Department of Agriculture (USDA), with a total of 47 human infections from poultry and dairy cattle sources, excluding 11 human cases from Washington state , that might belong to genotype D1.1, also reported.  Wild and domestic animals (e.g., cats, raccoons) near infected herds have been affected as well.  The outbreak remains uncontrolled .  Due to the unprecedented spread of the virus among ...