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Intranasal #influenza virus-vectored #vaccine offers protection against clade 2.3.4.4b #H5N1 #infection in small animal #models

Abstract The highly pathogenic avian influenza (HPAI) H5N1 virus has been endemic in aquatic birds since 1997, causing outbreaks in domestic poultry and occasional human infections worldwide. Recently, the cross-species transmission of a new reassortant variant from clade 2.3.4.4b of H5N1 to cattle in the US has heightened concerns regarding the expansion of host range and potential human infection . As eradicating the H5N1 virus from its reservoir is impossible, it is essential to prepare for a potential pandemic caused by an H5N1 derivative. Utilizing a deleted-NS1 live attenuated influenza viral vector vaccine system (DelNS1 LAIV), a system we have previously used in the development of a COVID-19 vaccine, we have rapidly developed an intranasal vaccine for cattle H5N1 and related clade 2.3.4.4b strains, based on publicly available sequences. Our research demonstrates that a single intranasal immunization can provide effective protection against lethal challenges from HPAI cattle or ...

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

On 31 March 2025 a clinical suspicion was reported to the Danish Veterinary and Food Administration. The affected poultry holding consists of 24 hens. On 1 April 2025 highly pathogenic avian influenza subtype H5N1 was confirmed by the national reference laboratory. A 3 km protection zone and a 10 km surveillance zone has been established. The culling was completed on 1 April 2025. Carcasses will be disposed of by rendering. Source: WOAH,  https://wahis.woah.org/#/in-review/6392 ____

#PA and #PAX: two key #proteins from segment 3 of the #influenza viruses

Abstract In recent years, the influenza viruses have posed an increasingly severe threat to public health . It is essential to analyze the virulence and pathogenesis of influenza viruses to prevent and control them, as well as create antiviral drugs . Previous studies have revealed that influenza virus segment 3 codes for not only the PA protein but also a novel protein, PA-X . PA protein is one subunit of the polymerase of influenza viruses and plays a critical role in its life cycle. PA presented endonuclease activity , the transcription and replication of the viral genome , viral virulence , protein degradation , and host immune response by interacting with viral proteins, including PB2, PB1, and host factors, including ANP32A, CHD6, HAX1, hCLE, HDAC6, MCM complex. PA mutations were involved in the viral replication, pathogenicity, and transmission of influenza viruses in poultry, mammals, and humans . PA-X is an open reading frame generated by +1 ribosomal code shift at the N-termi...

Introducing a #framework for within-host #dynamics and #mutations modelling of #H5N1 #influenza infection in #humans

Abstract Avian influenza A(H5N1) poses a public health risk due to its pandemic potential should the virus mutate to become human-to-human transmissible. To date, reported influenza A(H5N1) human cases have typically occurred in the lower respiratory tract with a high case fatality rate. There is prior evidence of some influenza A(H5N1) strains being a small number of amino acid mutations away from achieving droplet transmissibility , possibly allowing them to be spread between humans. We present a mechanistic within-host influenza A(H5N1) infection model, novel for its explicit consideration of the biological differences between the upper and lower respiratory tracts. We then estimate a distribution of viral lifespans and effective replication rates in human H5N1 influenza cases. By combining our within-host model with a viral mutation model, we determine the probability of an infected individual generating a droplet transmissible strain of influenza A(H5N1) through mutation. For thre...

#Population #Immunity to #HA Head, Stalk and #NA of HP Avian #Influenza 2.3.4.4b A(#H5N1) viruses in #USA and Impact of Seasonal Influenza on A(H5N1) Immunity

Abstract The unprecedented 2.3.4.4b A(H5N1) outbreak in dairy cattle, poultry, and spillover to humans in the United States (US) poses a major public health threat . Population immunity is a critical component of influenza pandemic risk assessment. We conducted a comprehensive assessment of the population immunity to 2.3.4.4b A(H5N1) viruses and analyzed 1794 sera from 723 people (0.5-88 yrs) in multiple US geographic regions during 2021-2024. Low pre-existing neutralizing and hemagglutinin (HA) head binding antibodies and substantial cross reactive binding antibodies to N1 neuraminidase (NA) of 2.3.4.4b A(H5N1) were detected in US population. Antibodies to group 1 HA stalk were also prevalent with an age-related pattern. A( H1N1 )pdm09 infection and influenza vaccination did not induce neutralizing antibodies but induced significant rise of NA inhibition (NAI) antibodies to N1 of 2.3.4.4b A(H5N1), and group 1 HA stalk antibodies. Understanding population susceptibility to novel influe...

#Influenza at the #human - #animal #interface - #Summary and #risk #assessment, from 21 January to 19 March 2025 {WHO}

Influenza at the human-animal interface Summary and risk assessment, from 21 January to 19 March 2025 {1}  New human cases {2}:  From 21 January to 19 March 2025, based on reporting date , the detection of influenza A( H5N1 ) in five humans, influenza A( H9N2 ) virus in four humans, influenza A( H1N1 ) variant ((H1N1)v) virus in one human, and influenza A( H1N2 )v virus in one human were reported officially.  • Circulation of influenza viruses with zoonotic potential in animals:  -- High pathogenicity avian influenza (HPAI) events in poultry and non-poultry 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 from these events. Based on information available at the time of the risk assessmen...

A #Human #H5N1 #Influenza Virus Expressing Bioluminescence for Evaluating Viral #Infection and Identifying #Therapeutic Interventions

Abstract A multistate outbreak of highly pathogenic avian influenza virus (HPAIV) H5N1 in dairy cows was first reported on March 25, 2024, in the United States (US), marking the first discovery of HPAIV H5N1 in cattle. Soon after, a dairy worker on an affected dairy farm became the first human case linked directly to this outbreak. Studies with influenza A virus (IAV) require secondary methods to detect the virus in infected cells or animal models of infection. We modified the non-structural (NS) genome segment of the human A/Texas/37/2024 (HPhTX) H5N1 virus to create a recombinant virus expressing nanoluciferase (HPhTX NSs-Nluc), enabling the tracking of virus in cultured cells and mice via in vitro, ex vivo, and in vivo imaging systems (IVIS). In vitro, HPhTX NSs-Nluc showed growth and plaque characteristics similar to its wild-type (WT) counterpart. In vivo, HPhTX NSs-Nluc allowed tracking viral infection in the entire animals and in the organs of infected animals using in vivo and ...

A Live Attenuated #Vaccine Candidate against Emerging Highly Pathogenic #Cattle-Origin 2.3.4.4b #H5N1 Viruses

Abstract Influenza viruses present a significant public health risk , causing substantial illness and death in humans each year. Seasonal flu vaccines must be updated regularly, and their effectiveness often decreases due to mismatches with circulating strains. Furthermore, inactivated vaccines do not provide protection against shifted influenza viruses that have the potential to cause a pandemic. The highly pathogenic avian influenza H5N1 clade 2.3.4.4b is prevalent among wild birds worldwide and is causing a multi-state outbreak affecting poultry and dairy cows in the United States (US) since March 2024. In this study, we have generated a NS1 deficient mutant of a low pathogenic version of the cattle-origin human influenza A/Texas/37/2024 H5N1 , namely LPhTXdNS1, and validated its safety, immunogenicity, and protection efficacy in a prime vaccination regimen against wild-type (WT) A/Texas/37/2024 H5N1 . The attenuation of LPhTXdNS1 in vitro was confirmed by its reduced replication in...

Couple with Parrot, Pieter de Hooch (1668)

  Public Domain. Source: WikiArt,  https://www.wikiart.org/en/pieter-de-hooch/couple-with-parrot-1668 ____

#Coronavirus Disease Research #References (by AMEDEO, March 30 '25)

  Ann Intern Med GRANWEHR BP CBT and rehabilitation improved long COVID symptoms. Ann Intern Med. 2025;178:JC28. PubMed           Abstract available BMJ WISE J Covid-19: Inquiry hears of doctors' lack of confidence in PPE as ministers defend VIP lane. BMJ. 2025;388:r584. PubMed          Clin Infect Dis ALLAN-BLITZ LT, Klausner JD Shifting the Focus in Acute SARS-CoV-2 Management to Include Prevention of Long-COVID. Clin Infect Dis. 2025 Mar 26:ciaf158. doi: 10.1093. PubMed          Emerg Infect Dis SANDER B, Mishra S, Swayze S, Sahakyan Y, et al Population-Based Matched Cohort Study of COVID-19 Healthcare Costs, Ontario, Canada. Emerg Infect Dis. 2025;31:710-719. PubMed           Abstract available Intensive Care Med BIHLMAIER K, Willam C, Herbst L, Hackstein H, et al Rapid clinical effects of convalescent plasma therapy in severe COV...

#Influenza and Other Respiratory Viruses Research #References (by AMEDEO, March 30 '25)

  Ann Intern Med GRANWEHR BP CBT and rehabilitation improved long COVID symptoms. Ann Intern Med. 2025;178:JC28. PubMed           Abstract available IOANNOU GN, Berry K, Rajeevan N, Li Y, et al Effectiveness of the 2023-to-2024 XBB.1.5 COVID-19 Vaccines Over Long-Term Follow-up : A Target Trial Emulation. Ann Intern Med. 2025 Feb 4. doi: 10.7326/ANNALS-24-01015. PubMed           Abstract available Antiviral Res KUO YS, Chiang PC, Kuo CY, Huang CG, et al Inhibition of influenza A virus proliferation in mice via universal RNA interference. Antiviral Res. 2025 Mar 25:106149. doi: 10.1016/j.antiviral.2025.106149. PubMed           Abstract available Arch Virol YE QY, Jiang ZT, Jiang Y, Cai JW, et al Effectiveness of inactivated COVID-19 vaccine against symptom severity in hospitalized COVID-19 patients infected with the Omicron variant. Arch Virol. 2025;170:88. PubMed ...

Modeling the #impact of early #vaccination in an #influenza #pandemic in the #USA

Abstract We modeled the impact of initiating one-dose influenza vaccination at 3 months vs 6 months after declaration of a pandemic over a 1-year timeframe in the US population. Three vaccine effectiveness (VE) and two pandemic severity levels were considered, using an epidemic curve based on typical seasonal influenza epidemics. Vaccination from 3 months with a high, moderate, or low effectiveness vaccine would prevent ~95%, 84%, or 38% deaths post-vaccination, respectively, compared with 21%, 18%, and 8%, respectively following vaccination at 6 months, irrespective of pandemic severity. While the pandemic curve would not be flattened from vaccination from 6 months , a moderate/high effectiveness vaccine could flatten the curve if administered from 3 months. Overall, speed of initiating a vaccination campaign is more important than VE in reducing the health impacts of an influenza pandemic. Preparedness strategies may be able to minimize future pandemic impacts by prioritizing rapid v...

#Molecular #epidemiology of #Kyasanur Forest Disease employing ONT-NGS a field forward #sequencing

Highlights •  The present analysis addresses the paucity of genetic information available for the recently emerged KFDV strains. •  As the virus is classified as a highly dangerous pathogen, it is essential to expand the existing genetic information. •  Continuous surveillance of the virus is essential for the development of a vaccine. •  The present study presents new findings on the KFD virus strains that were introduced into circulation in the period 2018-2020. •  The nanopore sequencing technology is presented as a proof of concept for the provision of early warnings in the field. Abstract The future of infectious agent detection and molecular characterization lies in field-forward, on-site strategies . The lack of genomic information for recently circulating Kyasanur Forest Disease virus strains is critical. Kyasanur Forest Virus Disease virus PCR-positive samples from 2018 to 2020 were selected for sequencing. Detailed molecular phylogenetic analyses were ...

Heterogeneity across #mammalian- and #avian-origin A(#H1N1) #influenza viruses influences viral infectivity following incubation with host #bacteria from the human respiratory tract

Abstract Influenza A viruses (IAV) are primarily transmitted between mammals by the respiratory route , and encounter bacteria in the respiratory tract before infecting susceptible epithelial cells. Previous studies have shown that mammalian-origin IAV can bind to the surface of different bacterial species and purified bacterial lipopolysaccharides (LPS), but despite the broad host range of IAV, few studies have included avian-origin IAV in these assessments. Since IAV that circulate in humans and birds are well-adapted to replication in the human respiratory and avian gastrointestinal tracts , respectively, we investigated the ability of multiple human and avian A(H1N1) IAV to associate with bacteria and their surface components isolated from both host niches. Binding interactions were assessed with microbial glycan microarrays, revealing that seasonal and avian IAV strains exhibited binding diversity to multiple bacterial glycans at the level of the virus and the bacterium, independe...

#Cholera - #Angola {WHO D.O.N. March 28 '25}

{Summary} Situation at a glance Since January 2025, Angola has been experiencing a substantial cholera outbreak . As of 23 March 2025, a total of 8543 cases and 329 deaths (Case Fatality Rate (CFR) 3.9% ) have been reported, with one-third of the deaths occurring in the community. The outbreak has rapidly spread to 16 out of Angola’s 21 provinces , affecting individuals of all age groups , with the highest burden among those under 20 years old . The Ministry of Health, with support from WHO and partners, is managing the cholera outbreak response through case detection, deployment of rapid response teams, community engagement and a vaccination campaign. Given the rapidly evolving outbreak, ongoing rainy season, and cross-border movement with neighbouring countries, WHO assesses the risk of further transmission in Angola and surrounding areas as very high. (...) Source: World Health Organization,  https://www.who.int/emergencies/disease-outbreak-news/item/2025-DON562 ____

Avian #Influenza Virus #Surveillance Across #NZ and Its Subantarctic #Islands Detects #H1N9 in Migratory #Shorebirds, but Not 2.3.4.4b HPAI #H5N1

Abstract Highly pathogenic avian influenza (HPAI) virus subtype H5N1 has never been detected in New Zealand . The potential impact of this virus on New Zealand's wild birds would be catastrophic. To expand our knowledge of avian influenza viruses across New Zealand, we sampled wild aquatic birds from New Zealand, its outer islands and its subantarctic territories. Metatranscriptomic analysis of 700 individuals spanning 33 species revealed no detection of H5N1 during the annual 2023-2024 migration. A single detection of H1N9 in red knots (Calidris canutus) was noted. This study provides a baseline for expanding avian influenza virus monitoring in New Zealand. Source: US National Library of Medicine,  https://pubmed.ncbi.nlm.nih.gov/40148670/ ____