Divergent avian #strains drive an off-season #influenza A #peak in municipal #wastewater

 

Abstract

Wastewater sequencing is an increasingly valuable tool in tracking the spread of infectious disease agents across space and time in areas of dense human settlement. Among pathogens that can be readily detected by this approach is influenza A, which follows predictable patterns of prevalence through the winter months in North America. Here, we leverage routine surveillance of a municipal wastewater treatment plant in Northern California to describe an atypical, off-season spike in influenza A concentrations that rivals that of the winter respiratory virus season. Drawing upon metagenomic data generated through hybrid-capture sequencing, we assemble and subsequently characterize fragments of divergent influenza genomes that appear to derive predominantly from the avian H16 clade. These strains exhibit close evolutionary relationships to influenza isolated from migratory shorebirds, hinting at potential host species and mechanisms of geographic spread. Analysis of read abundances suggest that these avian strains dominate the pool of influenza circulating during the summer months, when typical human-infecting strains are essentially absent. Together, our results expand the value of wastewater sequencing to encompass sensitive tracking of outbreaks within animals in interface regions where human settlement abuts wildlands, increasing overall pandemic preparedness.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This project was supported by a gift from the Sergey Brin Family Foundation to A.B.B.

Source: 

Link: https://www.medrxiv.org/content/10.64898/2026.04.02.26350079v1

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Broad #protection against #Influenza A Viruses via an adjuvant-free #mucosal microparticle #vaccine with conserved CD8/CD4 bispecific peptides

 

Abstract

Influenza A viruses (IAVs) cause substantial global morbidity and mortality and are responsible for most known viral pandemics. Their rapid antigenic evolution enables escape from natural and vaccine-induced immunity, requiring annual vaccine reformulation, which offers limited breadth and variable effectiveness. Although a universal influenza vaccine remains a critical objective, most strategies have focused on conserved viral glycoproteins to elicit broadly neutralizing antibodies, with comparatively fewer efforts targeting conserved T cell antigens to achieve cross-subtype protection. Current T cell-based approaches often rely on individual CD8+ epitopes, which are limited by peptide instability, delivery constraints, and dependence on adjuvants. Here, we demonstrate a T cell-focused vaccine strategy that uses evolutionary consensus of IAV M1 and NP from the H1N1 and H3N2 subtypes to predict, map, and screen conserved regions enriched with multiple CD8+ and CD4+ epitopes. We selected the top-performing peptides from immunogenicity screening. We encapsulated them in polylactic-co-glycolic acid microparticles (PLGA-MPs) engineered for selective uptake by APCs and pH-dependent sustained release. Intranasal delivery of this vaccine formulation targeted the primary site of infection and induced robust mucosal immunity without the need for conventional adjuvants. Both human and murine influenza-experienced T cells mounted potent recall responses to the vaccine. In mice, immunization elicited strong CD8+ and CD4+ T cell responses and conferred broad protection against homologous H1N1 and H3N2 as well as heterologous H5N1 IAV subtypes. These findings collectively establish a mucosal, T cell-based vaccine platform that is adjuvant-free and capable of providing broad protection against IAV and other viruses with pandemic potential.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

DBT-ENDFLU, BT/IN/EU-INF/15/RV/19-20

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.03.29.715080v1

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Antiviral activities of multiple #antivirals against highly pathogenic avian #influenza A #H5N1 in vitro and in mice

 

ABSTRACT

In 2024, a bovine H5N1 strain was first isolated from dairy cows in Texas and confirmed to transmit cross-species to humans. Therefore, research on treatments for human infection should be accelerated. In our study, the antiviral effects of baloxavir acid (BXA), oseltamivir carboxylate (OSC), EIDD-1931 (NHC), and ribavirin (RBV) against five H5N1 strains were evaluated in vitro. Cell viability and viral replication were measured to assess the antiviral effects. The results showed that the EC50 of BXA treatment was the lowest. The BXA/NHC and BXA/OSC combination treatments showed more potent inhibitory effects than each monotherapy. The 15 mg/kg baloxavir marboxil (BXM) / 125 mg/kg molnupiravir (MNP) and the 15 mg/kg BXM / 10 mg/kg oseltamivir phosphate (OSP) were tested in BALB/c mice. The mice were inoculated with 10 times the 50% mouse lethal dose (10 MLD50) of bovine H5N1 virus. Treatments began 1-day post-infection (1 dpi) and were administered orally twice daily for 5 or 7 days. Changes in body weight, clinical signs, and survival were monitored; lung and brain tissues were collected for virological, immunological, and histological analyses. Most mice died from severe neurological symptoms. Compared with the 5-day treatment, the 7-day treatment effectively inhibited viral replication and increased survival rates to 50% in BXM, BXM/MNP, and BXM/OSP treatments. Mice treated with BXM/MNP or BXM/OSP combination therapy showed lower viral yields in the lungs than those treated with BXM alone. The results provide a reference for human treatment, and extending the 7-day combination treatment should be considered.

Source: Emerging Microbes and Infections, https://www.tandfonline.com/journals/temi20

Link: https://www.tandfonline.com/doi/full/10.1080/22221751.2026.2645843

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A Live Attenuated #Vaccine Candidate against Emerging Highly Pathogenic #Cattle-Origin 2.3.4.4b #H5N1 [#Influenza] 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 cultured cells and inability to control IFNβ promoter activation. In C57BL/6J mice, LPhTXdNS1 has reduced viral replication and pathogenicity compared to WT A/Texas/37/2024 H5N1. Notably, LPhTXdNS1 vaccinated mice exhibited high immunogenicity that reach its peak at weeks 3 and 4 post-immunization, leading to robust protection against subsequent lethal challenge with WT A/Texas/37/2024 H5N1. Altogether, we demonstrate that a single dose vaccination with LPhTXdNS1 is safe and able to induce protective immune responses against H5N1. Both safety profile and protection immunity suggest that LPhTXdNS1 holds promise as a potential solution to address the urgent need for an effective vaccine in the event of a pandemic for the treatment of infected animals and humans.

Competing Interest Statement

The A.G.-S. laboratory has received research support from GSK, Pfizer, Senhwa Biosciences, Kenall Manufacturing, Blade Therapeutics, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Pharmamar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-fold LLC, Model Medicines, Atea Pharma, Applied Biological Laboratories and Merck. A.G.-S. has consulting agreements for the following companies involving cash and/or stock: Castlevax, Amovir, Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Pagoda, Accurius, Esperovax, Applied Biological Laboratories, Pharmamar, CureLab Oncology, CureLab Veterinary, Synairgen, Paratus, Pfizer and Prosetta. A.G.-S. has been an invited speaker in meeting events organized by Seqirus, Janssen, Abbott, Astrazeneca and NovavaxA.G.-S. is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York. All other authors declare no commercial or financial conflict of interest.

Source: 

Link: https://www.biorxiv.org/content/10.1101/2025.03.28.646033v2

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Deciphering #HPAI #Influenza A Virus #H5N1: Molecular Basis of #Pathogenicity, Zoonotic Potential, and Advances in #Vaccination Strategies

 

Abstract

The ongoing panzootic of the highly pathogenic avian influenza (HPAI) H5N1 virus, dominated by clade 2.3.4.4b, constitutes a significant global threat to wildlife, animal health, and public health. Once characterized by sporadic outbreaks, H5N1 has evolved into a sustained, year-round infection with an expanded host range that now includes numerous mammalian species. Its high pathogenicity is primarily driven by the acquisition of a polybasic haemagglutinin cleavage site, enabling systemic viral spread, alongside emerging endothelial and neurotropic properties that contribute to severe disease and high mortality in mammals. Although zoonotic transmission remains limited, H5N1 continues to accumulate mutations associated with mammalian adaptation, particularly within the haemagglutinin and polymerase complex. Notably, recent outbreaks in U.S. dairy cattle highlight the emergence of novel mammalian reservoirs with increased human exposure risk. Concurrently, vaccination strategies are advancing beyond traditional adjuvanted inactivated vaccines toward next-generation platforms, including mRNA and virus-like particle vaccines, designed for rapid deployment and broader immune protection. However, ongoing viral evolution, constrained vaccine availability, and gaps in coordinated surveillance underscore the urgent need for an integrated One Health approach to reduce panzootic risk.

Source: 

Link: https://www.mdpi.com/1999-4915/18/4/410

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Mapping #global emergence of #pathogens with #epidemic and #pandemic #potential to inform and accelerate pandemic #prevention, #preparedness, readiness and response

 

Abstract

Introduction 

Increasing occurrence of epidemics and pandemics and concurrent emergence of different pathogens calls for multi-sectoral, multi-pathogen preparedness actions. Data on various factors that drive emergence of diverse pathogens can inform evidence-based preparedness by identifying geographies at-risk. When leveraging evidence within a One Health approach, multiple pathogens can be addressed simultaneously, thereby strengthening countries pandemic preparedness efforts. 

Methods 

For seventeen priority pathogens (avian influenza viruses, zoonotic coronaviruses including COVID-19, hemorrhagic fever viruses including Ebola, Henipaviruses, and arboviruses including yellow fever and Zika), we identified global evidence on animal reservoirs, vectors, environmental suitability, and reported human cases. We discriminated geospatially recorded pathogen detections from a background sample and constructed maps using these datasets to generate an evidence-based assessment of emergence risk globally. 

Results 

Seventeen pathogen-specific assessments were combined into a global composite map. Sub-Saharan Africa and South Asia have evidence supporting emergence risk for the greatest number of pathogens (included areas at-risk of all pathogens) and scored highest when strength-of-evidence weightings were factored. The Americas had the lowest tally of considered pathogens. Environmental suitability analyses received the highest weights, reservoir ranges the lowest. 

Discussion 

Preparedness and readiness must consider the range of global biological threats. Our methodology is capable of incorporating changing evidence on emergence potential for multiple pathogens to identify geographies at higher risk with different pathogen combinations. Our maps can contribute to existing decision-support structures, guiding shared interventions and strategic allocation of resources for spillover prevention and pandemic preparedness, thereby enhancing local response capacities applying a multidisciplinary approach.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This work was concluded in 2024 and supported by the United States Agency for International Development (USAID) before January 22, 2025, the Germany Agency for International Cooperation (GIZ) and the Government of France.

Source: 

Link: https://www.medrxiv.org/content/10.64898/2026.03.20.26347940v1

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Prophylactic and therapeutic efficacy of #monoclonal #antibodies against #H5N1 #influenza virus

 

Highlights

• mAbs could enhance our armamentarium against H5N1 in support of pandemic preparedness

• Several mAbs have shown prophylactic and therapeutic efficacy against H5N1 in animal models

• Anti-IAV mAbs that have advanced in clinical trials could be evaluated against H5N1

• Resistance emergence during mAb treatment was infrequent in pre- and clinical studies

Abstract

Highly pathogenic avian influenza H5N1 continues to pose a serious zoonotic and pandemic threat due to its increasing cross-species transmission and high virulence in humans. Despite the availability of vaccines and antivirals for seasonal influenza, effective prophylactic and treatment options for H5N1 remain limited. Herein we explore the potential action of monoclonal antibodies (mAbs) against H5N1, focusing on those with demonstrated efficacy in animal models. Most of these mAbs target conserved hemagglutinin epitopes and function as broad neutralizing fusion/entry inhibitors; notably, CR9114 targets both groups 1 and 2 influenza A strains as well as B lineages. Other mAbs prevent viral release by targeting neuraminidase, and those directed against the M2 ectodomain and nucleoprotein function through Fc receptor-mediated pathways. These mAbs have shown robust protection against lethal H5N1 challenge in mice, ferrets, and/or non-human primates. Compounds such as CR6261, MEDI8852, and TCN-032 have been evaluated in clinical trials for seasonal influenza, yielding encouraging safety and pharmacokinetics results and notably, no reported emergence of resistance. Despite these positive results their clinical development was prematurely discontinued. Integrating these highly effective mAbs into our H5N1 pandemic preparedness arsenal is a logical next step to provide a robust prophylactic and therapeutic option at the early stages of an outbreak. Future efforts must address regulatory and logistical barriers, invest in stockpiling and emergency use protocols, and support adaptive clinical trial frameworks to ensure rapid deployment when needed.

Source: 

Link: https://www.sciencedirect.com/science/article/pii/S0924857926000737?via%3Dihub

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Behavioural determinants of #testing behaviour during a hypothetical avian #influenza #outbreak: an interview study

 

Abstract

Background: 

Avian Influenza (AI) is a potential pandemic threat, specifically when human-to-human transmission occurs. For outbreak management testing is essential. Current knowledge on testing behaviour is mostly derived from other infectious diseases such as COVID-19. It is necessary to identify determinants of testing behaviour for AI in an early phase. Therefore, this interview study aims to identify a wide range of behavioural determinants of testing during a hypothetical human-to-human transmissible AI outbreak. 

Methods: 

Semi-structured in-depth interviews, based on the Theoretical Domains Framework, were carried out between May 2024 and February 2025. Participants were included through purposive and convenience sampling. During the interviews an animation was shown illustrating a hypothetical AI outbreak. Verbatim transcripts were thematically analysed. 

Results: 

We included seventeen participants (median age 44, range 20-81; 71% women) with diverse backgrounds in terms of age, gender, educational level and country of birth. We found that having the freedom to decide to test would make testing more acceptable, whereas a decreased sense of autonomy would discourage testing. Most themes included individual rather than population-level benefits as drivers of testing behaviour. These included protecting loved ones, one's own health and gaining psychological reassurance. External conditions like being unable to go to work or an event would generally encourage testing behaviour. Lower trust in governmental authorities could hamper testing behaviour. Previous experiences from the COVID-19 pandemic shaped the participants' answers about AI testing behaviour. 

Conclusion: 

Key considerations include balancing people's need for autonomy with the external measures imposed by employers or the government, rebuilding trust in institutions and acknowledging how prior experiences with testing may shape testing behaviour in future AI outbreaks. Further research is needed to determine how these findings can be translated into effective communication and how trust in authorities can be build.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study was supported by ZonMw (projectnumber 10710032310014) an organisation that stimulates innovations to improve healthcare in the Netherlands. The funder had no involvement in study design, data collection, analysis, interpretation of the findings or in manuscript preparation.

Source: 

Link: https://www.medrxiv.org/content/10.64898/2026.03.17.26348610v1

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Optimizing an avian #influenza #vaccine using a novel Bacterial Enzymatic Combinatorial Chemistry (BECC) TLR4 #adjuvant

 

Abstract

The development of broadly protective and dose-sparing influenza vaccines remains a critical challenge, particularly for zoonotic H5N1 strains with pandemic potential. This study evaluates BECC470s, a synthetic TLR4 adjuvant, for its ability to enhance the immunogenicity and protective efficacy of recombinant H5 hemagglutinin (rHA) vaccination in murine models. BECC470s-adjuvanted rHA elicited robust IgG1/IgG2a antibody responses and complete survival following homologous 2004 H5N1 challenge in a prime–boost model. Although BECC470s broadened antibody binding to both variable HA head and conserved stalk domains by ELISA, functional neutralizing antibody responses were restricted to the matched 2004 H5N1 isolate, with no detectable neutralization of H5N1 viruses isolated in 2022 or 2024. These data indicate that BECC470s enhances the magnitude and apparent breadth of binding antibody responses while maintaining strain-specific neutralizing activity, supporting its potential as an adjuvant for next-generation influenza vaccines while underscoring the need for further optimization to achieve true cross-neutralizing protection.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.03.03.709477v1

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Fatal #human #H3N8 #influenza virus has a moderate #pandemic #risk

 

Abstract

In China, low pathogenic avian influenza (LPAI) H3N8 virus is widespread among chickens and has recently caused three zoonotic infections, with the last one in 2023 being fatal. Here we evaluated the relative pandemic risk of this 2023 zoonotic H3N8 influenza virus, utilizing our previously published decision tree. Serological analysis indicated that a large proportion of the human population does not have any cross-neutralizing antibodies against this H3N8 strain. LPAI H3N8 displayed a dual affinity for α2–3 and α2–6 sialic acids and replicated efficiently in human bronchial epithelial cells. Furthermore, we observed H3N8 transmission via direct contact but not aerosols to ferrets with pre-existing H3N2 immunity. Although pre-existing H3N2 immunity resulted in a shortened disease course in ferrets, it did not reduce disease severity or replication in the respiratory tract. This study suggests that this zoonotic H3N8 strain has moderate pandemic potential and emphasizes the continued need for avian influenza surveillance.

Author summary

Low pathogenic avian influenza (LPAI) viruses circulate widely amongst birds and are a major public health concern for their ability to cross over to other species, including humans. Here we characterize the pandemic potential of an H3N8 LPAI virus that caused a lethal human infection. While this strain was only able to transmit by direct contact, we found that it did exhibit some human adaptations, and pre-existing immunity did not reduce replication or pathogenesis, suggesting that it is a moderate pandemic risk and needs to be monitored given the potential public health threat.

Source: 

Link: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1013586

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Potent efficacy of an NA-targeting #antibody against a broad spectrum of #H5N1 #influenza viruses

 

Abstract

For nearly 30 years, Goose/Guangdong-derived highly pathogenic avian influenza H5N1 viruses have posed significant risks to economic stability, food security, and public health. Virus evolution has resulted in various clades, including the panzootic subclade 2.3.4.4b, recognized for its pandemic potential. Here we present the potent in vitro activity of FNI9, a pan-influenza NA-inhibiting monoclonal antibody, against a range of pseudoparticles with NA spanning decades of H5N1 virus evolution. FNI9 also shows strong prophylactic protection in female mice against lethal challenges with H5N1 from clade 1 and 2.3.4.4b. Cryo-EM and molecular dynamics analysis reveal that FNI9 binds to 7 highly conserved H5N1 NA residues (R118, E119, D151, E228, E278, R293, and R368). In silico evolutionary escape profiling and machine learning predict low escapability, high fitness costs, and minimal spread likelihood for viral mutations that evade FNI9 binding. These findings support FNI9 broad protection and underscore the NA role in future influenza vaccine design.

Source: 

Link: https://www.nature.com/articles/s41467-026-70036-8

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#Development and Characterization of Candidate #Vaccine #Viruses against High Pathogenicity Avian #Influenza #H5 Viruses for Rapid #Pandemic Response

 

Abstract

High pathogenicity avian influenza A(H5) viruses pose a pandemic threat. These viruses have rapidly evolved in birds and frequently crossed species barriers, resulting in over 1,000 confirmed human infections, with a case fatality proportion of approximately 50%. In response, the U.S. CDC has developed dozens of A(H5) candidate vaccine viruses (CVVs) over the past two decades, primarily targeting clades known to infect humans. This report summarizes the development and characterization of the CVVs, with a particular focus on their antigenic relationships with clades 2.3.2.1e and 2.3.4.4b A(H5N1) viruses, which have been responsible for the majority of recent human infections.

Source: 

Link: https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiag132/8502029

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The #bovine mammary #gland as a crucible for zoonotic #influenza virus emergence: Receptor-mediated #adaptation of HPAI #H5N1 clade 2.3.4.4b

 

Abstract

The recent emergence of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b in U.S. dairy cattle marks a pivotal shift in the ecology of influenza A viruses (IAVs), signaling an unexpected expansion into a major livestock species. This review explores the molecular mechanisms underpinning this cross-species transmission, focusing on the unique sialic acid receptor landscape of the bovine mammary gland as a critical determinant. We synthesize emerging evidence that this tissue, which co-expresses both avian-type (α2,3-linked) and human-type (α2,6-linked) sialic acid receptors, functions as a novel biological crucible for viral adaptation. Within this environment, H5N1 virus faces selective pressure for hemagglutinin (HA) mutations—such as Q226L and N193D—that can alter receptor binding specificity toward human-like glycans, potentially bridging the species barrier. Recent studies confirm that bovine H5N1 virus isolates exhibit dual receptor-binding avidity and that single HA mutations are sufficient to shift binding preference to human receptors. The unprecedented mammalian spread of clade 2.3.4.4b, coupled with its capacity for reassortment and the recent case of a dairy farm worker infection, underscores an urgent zoonotic and pandemic threat. This review contextualizes the outbreak within the fundamental principles of influenza virus receptor biology and viral evolution, highlighting critical knowledge gaps that must be addressed through integrated surveillance and multidisciplinary research. Understanding the interplay between host receptor distribution and viral plasticity in this new niche is paramount for mitigating the risk of a future influenza virus pandemic emerging from the bovine reservoir.

Source: 

Link: https://link.springer.com/article/10.1007/s00705-026-06529-0

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#Baloxavir outperforms #oseltamivir, #favipiravir, and #amantadine in treating lethal #influenza #H5N1 HA clade 2.3.4.4b #infection in #mice

 

Abstract

Intercontinental spread of highly pathogenic avian influenza A(H5N1) viruses poses significant pandemic risks and necessitates strong protective countermeasures. We evaluated the therapeutic efficacy of the neuraminidase inhibitor oseltamivir, the polymerase inhibitors baloxavir and favipiravir, and an ion-channel blocker amantadine, against severe influenza A(H5N1) virus infection in female BALB/c mice. Baloxavir (≥10 mg/kg, 1 dose) fully protected mice from death, significantly reduced virus respiratory replication, and prevented neuroinvasion. Oseltamivir (≥100 mg/kg/day for 5 days) provided limited survival benefits, reduced lung titers but failed to prevent viral neuroinvasion. Favipiravir (≥100 mg/kg/day for 5 days) provided partial protection, although did not reduce viral titers in lungs and brain. Amantadine provided no benefits. Although all drugs inhibited A(H5N1) viruses in vitro, in vivo correlations did not extend beyond baloxavir. Our results indicate that baloxavir is the most reliable treatment to address both respiratory replication and systemic spread of contemporary A(H5N1) viruses in mice and should be considered in pandemic planning.

Source: 

Link: https://www.nature.com/articles/s41467-026-69721-5

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Zoonotic #Influenza #Preparedness: Dutch Medical #Labs Efficiently Detect Animal Influenza A Viruses - External #Quality #Assessment, 2023

 

Highlights

• Concern over H5N1 bird flu testing and detection in the Netherlands is increasing.

• 50 human laboratories in the Netherlands, Aruba, Bonaire, and Curacao were assessed.

• The laboratories detected animal influenza viruses with high performance.

• Few laboratories identified the animal subtype of detected influenza A viruses.

• National reference laboratory capacity to identify the animal subtype is critical.

Abstract

Background

Since 2022, highly pathogenic H5N1 influenza A virus clade 2.3.4.4b has caused global outbreaks among wild birds and poultry, with increasing mammalian and sporadic human infections. This elevates concerns about zoonotic transmission and pandemic risk, highlighting the need for accurate detection and identification of animal influenza A viruses by human clinical diagnostic laboratories (hCDL).

Methods

To evaluate routine diagnostic performance, an External Quality Assessment (EQA) panel containing inactivated influenza A viruses of avian (three subtype H5, one H7), swine (two H1, one H3), and human (one H1pdm09, one H3) origin was distributed to 50 hCDL in the Netherlands, Aruba, Bonaire, and Curaçao. Laboratories conducted their routine molecular influenza virus detection and, if available, subtyping workflows.

Results

A total of 118 detection workflows were reported. Of these, 109 (91%) successfully detected influenza A virus in all positive specimens. At least one workflow in 49/50 (98%) laboratories reliably detected all animal influenza viruses as type A influenza virus. Most false negatives occurred with swine H1N1v. Only 24 workflows from 20 laboratories attempted subtyping for one or multiple panel specimens (total 109 subtype-specific results reported): for human viruses, 37/39 results were correct; for avian viruses, 13/14 were correct (including 12/12 for H5); for swine viruses, only 2/56 were correct (both swine H3N2 using broad-reactive H3 assays).

Conclusions

hCDL in the Netherlands demonstrate high performance for detecting animal influenza A viruses. However, subtyping capacity is limited, necessitating referral of specimens of suspected zoonotic influenza cases to the National Influenza Centre for further characterization.

Source: 

Link: https://www.sciencedirect.com/science/article/abs/pii/S1386653226000168?dgcid=rss_sd_all

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Decoding #antibody response to #MERS-CoV in wild dromedary #camels

 

Significance

Middle East respiratory syndrome coronavirus (MERS-CoV) remains the most lethal human coronavirus, with continued zoonotic transmission from wild naturally infected dromedary camels, posing a persistent risk of spillover to humans. Despite this ongoing threat, no specific antiviral treatment has been approved. In this study, we characterize the antibody response to MERS-CoV in naturally infected dromedaries, the primary animal reservoir, and identify a panel of nanobodies (Nbs) exhibiting potent neutralizing activity. These Nbs recognize a previously unreported binding and neutralizing site on the virus spike receptor-binding domain (RBD). Their distinctive genetic, structural, and functional properties make them promising candidates for the development of effective and therapeutic interventions against MERS-CoV, as strongly advocated by global health authorities.

Abstract

Wild dromedary camels in the Arabian Peninsula and Africa have harbored antibodies against Middle East Respiratory Syndrome Coronavirus (MERS-CoV) for decades, predating zoonotic spillover to humans. However, the potency, specificity, and structural characteristics of these antibodies remain poorly understood. Here, we characterize the antibody responses of naturally infected wild dromedary camels in Tunisia, a MERS-CoV-endemic region. Plasma antibodies from nine camels exhibited variable neutralizing activity, generally increasing with age, and were largely autologous, with minimal cross-reactivity to SARS-CoV-1 or SARS-CoV-2. From a VHH antibody library derived from the peripheral blood mononuclear cells (PBMCs) of a single camel (D17), we identified 34 unique sequences with previously unreported germline origins and unusually long complementarity-determining region 3 (CDR3) sequences. Eight representative VHHs, expressed as human Fc fusions, displayed high-affinity binding to the MERS-CoV receptor-binding domain (RBD) and broad neutralization to RBD mutants (IC50: 1.05 to 9.55 ng/mL). Crystal structural analysis revealed distinct neutralization mechanisms: VHH-227 fully blocked DPP4 binding, achieving complete neutralization, while VHH-T71, with partial neutralization (~80%), targeted the RBD core subdomain. This study provides comprehensive characterization of wild dromedary antibody responses, identifying novel nanobodies (Nbs) with broad and potent neutralization to naturally occurring RBD mutants. These findings offer insights into camel immunity and highlight promising candidates for MERS-CoV prophylactic and therapeutic development.

Source: 

Link: https://www.pnas.org/doi/10.1073/pnas.2513716123

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Avian #Influenza #H5N1 #Infection During #Pregnancy: Preparing for the Next Flu #Pandemic and Improving Perinatal Outcomes

 

Abstract

Influenza (flu) is a common respiratory virus with seasonal global spread. Zoonotic viruses can occasionally cross species, leading to pandemic-level spread, and for flu viruses, this is considered an “antigenic shift”. The flu can be particularly severe during pregnancy due to immune system adaptations that occur during pregnancy, with prior global pandemics causing excess hospitalizations, deaths, and other complications in the mothers and the neonates. We aim to review the current literature with respect to novel avian H5N1 and the potential impact of infection with flu during pregnancy. A systematic literature search was conducted. Here we provide a rapid summary of epidemiology and understanding of viral spread, published risks of H5N1 in pregnancy, the unique physiologic, cellular, and molecular adaptations making H5N1 infection unique in pregnancy, implementation of an effective vaccine program in event of a pandemic specific to pregnant individuals, optimizing peripartum care for infected individuals, and direction for future research to direct vaccine strategy and mitigate risks in a future flu pandemic.

Source: 

Link: https://www.mdpi.com/1999-4915/18/2/212

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A stabilized #MERS-CoV #spike ferritin #nanoparticle #vaccine elicits robust and protective neutralizing #antibody responses

 

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) was identified as a human pathogen in 2012 and causes ongoing sporadic infections and outbreak clusters. Despite case fatality rates (CFRs) of over 30% and considerable pandemic potential, a safe and efficacious vaccine has not been developed. Here we report the design, characterization, and preclinical evaluation of MERS-CoV antigens. Our lead candidate comprises a stabilized spike displayed on a self-assembling ferritin nanoparticle that can be produced from a high-expressing, stable cell pool. This vaccine elicits robust MERS-CoV pseudovirus and authentic virus neutralizing antibody titers in BALB/c mice. Immunization of male non-human primates (NHPs) with one dose of Alhydrogel-adjuvanted vaccine elicited a > 103 geometric mean titer of pseudovirus neutralizing antibodies that was boosted with a second dose. Sera from these NHPs exhibited cross-reactivity against spike-pseudotyped lentiviruses from MERS-CoV clades A, B, and C as well as a distant pangolin merbecovirus. In human DPP4 transgenic mice, immunization provided dose-dependent protection against MERS-CoV lethal challenge, and in an established alpaca challenge model using female alpacas, immunization fully protected against MERS-CoV infection. This MERS-CoV nanoparticle vaccine is a promising candidate for clinical advancement to protect at-risk individuals and for future use in a potential outbreak setting.

Source: 

Link: https://www.nature.com/articles/s41467-026-68458-5

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Advancing #H5N1 #influenza #risk #assessment in #ferrets through comparative evaluation of airborne virus shedding patterns

 

Abstract

Recent A(H5N1) zoonotic cases linked to poultry and cattle in North America highlight the urgent need to assess the pandemic potential of emerging strains. Using male ferrets, we evaluate two B3.13 and two D1.1 genotype A(H5N1) viruses isolated from humans and observe fatal disease and varying capacities for direct contact transmission. To enhance pandemic risk assessment, we conduct aerosol sampling using cyclone BC251 and water condensation capture-based SPOT samplers and perform comparative analyses to include additional A(H5N1), A(H9N2), A(H7N9), and A(H1N1)pdm09 strains with known transmissibility profiles. Although none of the A(H5N1) strains transmit via the air, B3.13 viruses are detected at significantly higher levels compared to D1.1 strains. Here we show strong correlations between viral loads in nasal washes, airborne virus shedding, and transmissibility in ferrets, highlighting the value of these metrics for identifying zoonotic influenza viruses that may be adapting toward increased transmission potential.

Source: 

Link: https://www.nature.com/articles/s41467-026-68931-1

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An intranasal adenoviral-vectored #vaccine protects against highly pathogenic avian #influenza #H5N1 in naive and antigen-experienced #animals

 

Highlights

• IN-delivered ChAd-Texas vaccine elicits mucosal antibody and T cell responses

• IN-delivered ChAd-Texas vaccine protects against H5N1 in mice and hamsters

• IN delivery of ChAd-Texas vaccine confers greater protection than IM delivery

• ChAd-Texas induces H5N1 immunity in the setting of prior influenza immunity

Summary

The emergence of highly pathogenic avian H5N1 influenza viruses in dairy cows and humans has increased the potential for another pandemic. To address this risk, we developed chimpanzee adenoviral (ChAd)-vectored H5 hemagglutinin-targeted vaccines and tested their immunogenicity and efficacy in rodents. Immunization with ChAd-Texas (clade 2.3.4.4b) vaccine in mice elicits neutralizing antibody responses and confers protection against viral infection and mortality upon challenge with a human H5N1 isolate (A/Michigan/90/2024, clade 2.3.4.4b). Intranasal delivery of the ChAd-Texas vaccine elicits mucosal antibody and T cell responses and confers greater protection than intramuscular immunization. In Syrian hamsters, a single intranasal dose of ChAd-Texas vaccine prevents weight loss and reduces airway infection after H5N1 A/Michigan/90/2024 or A/Texas/37/2024 challenge. Importantly, prior seasonal influenza vaccination does not impair antibody responses or protection after intranasal delivery of the ChAd-Texas vaccine. These results support the development of mucosally administered ChAd-Texas HA vaccines as an effective platform for HPAI H5N1 preparedness.

Source: 

Link: https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(25)00655-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS266637912500655X%3Fshowall%3Dtrue

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