Structural and functional characterization of the #antigenicity of #influenza A virus #hemagglutinin subtype #H15

Abstract

Avian H15 influenza viruses are closely related to H7 viruses, but feature a unique 9-amino acid insertion in their hemagglutinin head domain, creating an additional site for antigenic variation. Here, we characterized a panel of mouse monoclonal antibodies (mAbs) raised against the A/wedge-tailed shearwater/Western Australia/2576/1979 ancestral strain, and a human mAb isolated from an H7N9 vaccinee. We found differences in binding and neutralization profiles against the ancestral strain and drifted strains of H15 isolated after 2008. MAbs that have hemagglutination inhibition activity against the ancestral strain do not show binding to drifted strains, hinting at antigenic differences in the receptor binding site. We show that the mAbs protect in vivo and elucidate mAb-antigen interactions using negative stain and cryo-electron microscopy. The characterization of H15 antigenicity and mechanisms of antibody-mediated neutralization expands our knowledge of this rare avian influenza virus and informs our understanding of immune pressures on viral surface glycoproteins.

Source:  BioRxIV, https://www.biorxiv.org/content/10.1101/2025.07.01.662631v1?rss=1

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

Two poultry farms affected in North West and Mpumalanga Regions.

Source: WOAH, https://wahis.woah.org/#/in-review/6585?reportId=175014&fromPage=event-dashboard-url

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#Influenza A Virus #infection is associated with TDP-43 #pathology and neuronal #damage in the #brain

Abstract

Viral pandemics such as COVID-19 have demonstrated long-term neurological consequences, including memory impairment and depression, emphasizing the importance of understanding virus-brain interactions [1]. Similar concerns have been raised for Influenza A virus (IAV), which has been implicated in neurodegenerative disorders [2, 3]. In this study, we investigated the neuropathological effects of highly pathogenic avian influenza (HPAI) H5N1 and H5N8 strains in a mouse model. Although viral RNA was detected in the brain post-infection, no viral proteins were found, suggesting limited or transient brain replication. Despite this, infected brains showed significant neuronal damage, including axonal loss and nuclear condensation, as evidenced by immunofluorescence and Nissl staining. We also observed pathological changes in TDP-43, including conformational alterations and increased phosphorylation, which required antigen retrieval for detection, features reminiscent of those found in frontotemporal dementia and amyotrophic lateral sclerosis [4, 5]. Transcriptomic analysis further revealed strain-specific host responses, including activation of interferon-related genes and downregulation of microtubule-associated pathways. These findings suggest that IAV infection can trigger hallmarks of neurodegeneration in the absence of persistent viral protein expression, possibly through host-driven mechanisms. Our results underscore the need for further investigation into virus-induced molecular pathways contributing to neurodegenerative disease.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.06.30.662477v1

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A 15-year study of #neuraminidase #mutations and the increasing of S247N mutation in #Spain

Highlights

• In a landscape of a very narrow arsenal of influenza antivirals, resistance mutations are a significant threat.

• Resistance mutations were present in 0.5-5% in A and B influenza viruses during the last 15 years.

• However, S247N resistance mutation in the NA gene sharply increased during 2023-2024 season.

• While this mutation does not confer strong resistance by itself, their fixation could increase the risk of resistance in the future if other resistance mutations appears or get fixed together with it.

Abstract

The therapeutic arsenal against influenza is extremely limited and resistance often arises due to the emergence of mutations, especially in the neuraminidase (NA) gene. This study aimed to evaluate the evolution of NA mutations over 15 years in Spain. To do so, we used the GISAID database from which we downloaded a total of 11,125 influenza A(H1N1)pdm09, A(H3N2), B/Victoria and B/Yamagata NA virus sequences, and analyzed the resistance mutations using FluSurver software. Our results showed that the occurrence of NA resistance mutations remained constant in the four viruses during the 15 seasons evaluated, being around 0.5-5%. Most of the resistance was found in the A(H1N1)pdm09 subtype (around 70%), especially from the 2023-2024 season onwards, when a significant increase in the occurrence of S247N mutation was observed. The occurrence of this type of mutation before 2022 was rare, but in the 2023-2024 season a total of 44 influenza viruses harboring S247N mutations were detected, while in the other years, only two cases were observed. Some studies have described a significant increase in this mutation over the past two seasons and although it appears to confer only slightly reduced inhibition to oseltamivir, its increase is noteworthy and should be a reason for increased their vigilance.

Source: Virus Research, https://www.sciencedirect.com/science/article/pii/S0168170225000760?via%3Dihub

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A single-dose #intranasal #immunization with a novel #bat #influenza A virus-vectored #MERS #vaccine provides effective protection against lethal MERS-CoV challenge

ABSTRACT

The threat to global health security posed by Middle East respiratory syndrome coronavirus (MERS-CoV) and emerging MERS-like coronaviruses highlights the need to develop safe and efficient vaccines. Viral vector vaccines have been shown to be effective and are widely used to prevent various viral diseases because they mimic natural infection and induce a more comprehensive immune response. Herein, we developed a novel bat influenza A virus-based vaccine vector by replacing the open reading frame of either bat influenza hemagglutinin or neuraminidase with that of the hemagglutinin-esterase-fusion gene from influenza D virus, which can infect multiple species, including humans and camels. We then generated a temperature-sensitive, cold-adapted, and attenuated MERS vaccine candidate expressing the clade A MERS-CoV spike S1, referred to as Len_S1, using the developed bat influenza vector and demonstrated its safety and immunogenicity. A single-dose intranasal immunization with Len_S1 protected human dipeptidyl-peptidase-4 (hDPP4) transgenic mice from a lethal MERS-CoV challenge. Notably, a two-dose immunization with Len_S1 completely blocked viral replication and lung damage in challenged mice. Further studies revealed that intranasal immunization with Len_S1 in mice elicited mucosal, humoral, and cellular immune responses. Moreover, sera collected from Len_S1-immunized mice were able to cross-neutralize multiple clades of MERS-CoVs. Collectively, these results indicate that Len_S1 is a safe and effective MERS vaccine that induces a comprehensive immune response and provides cross-protection against diverse clades of MERS-CoVs.

Source: mBio, https://journals.asm.org/doi/10.1128/mbio.01107-25

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#Genetic #resilience or #resistance in #poultry against avian #influenza virus: mirage or reality?

ABSTRACT

The unprecedented global spread of the highly pathogenic avian influenza (HPAI) virus in wild birds, poultry, and mammalian species has challenged our control efforts. Alternative approaches to limit avian influenza viruses (AIV) include the development of resilient or resistant chickens. Genetically resilient birds may become infected but can overcome disease, whereas resistant birds prevent virus attachment or entry and do not become infected. The most intensively studied host gene is myxovirus-resistance (Mx), which is expressed via the interferon pathway. Both sensitive and resistant chicken Mx genotypes have been described, but this only provides limited resilience. Acidic nuclear phosphoprotein 32 family member A (ANP32A) has been demonstrated as a host cofactor for AIV replication via interaction with the polymerase. Small nucleotide changes within this gene have demonstrated some promise for the establishment of disease resilience. Certain MHC-defined genetic chicken lines have demonstrated increased resilience with higher innate immune responses, but HPAI-infected birds still have high morbidity and mortality. Alternatively, gene-edited or -transgenic chickens have had some success in increasing resilience. This strategy allows flexibility to include foreign genes, modification of existing genes, or combined approaches to block critical steps in the viral life cycle. Some candidate genes include solute carrier 35A1 (SLC35A1), retinoic acid-inducible gene I (RIG-I), and toll-like receptors 3 and 7 (TLR3/7), but animal testing needs to be conducted. Furthermore, existing hurdles for technology transfer to commercial application from either naturally occurring resistance genes or foreign genes remain high and will require acceptance by both the poultry industry and consumers.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.00820-25?af=R

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#Cambodia records 11th #human case of #H5N1 #birdflu in 2025

 

PHNOM PENH, July 1 (Xinhua) -- A 36-year-old woman from northwest Cambodia's Siem Reap province has been confirmed for H5N1 human avian influenza, raising the number of the cases to 11 so far this year, the Ministry of Health said in a statement on Tuesday.

"A laboratory result from the Pasteur Institute in Cambodia showed on June 30 that the woman was positive for H5N1 virus," the statement said. "The patient has the symptoms of fever, cough, and dyspnea, and she is currently being rescued by a team of doctors."

The victim lives in Doun Keo village of Puok district.

There were sick and dead chickens at the patient's home. She had been in contact with those dead chickens and took them to bury.

Health authorities are looking into the source of the infection and are examining any suspected cases or people who have been in contact with the victim in order to prevent an outbreak in the community.

Tamiflu (oseltamivir), an antiviral drug to prevent the bird flu from spreading, was also given out to people who had direct contact with the patient, the statement said.

So far this year, the kingdom recorded a total of 11 human cases of H5N1 bird flu, with five deaths, according to the Ministry of Health.

Source: Xinhua, https://english.news.cn/asiapacific/20250701/82062615bf9a44b1933b4dc3535823fb/c.html

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#Cambodia reported four additional #human cases of #infection with #influenza A #H5N1 virus during week 26/2025 (HK CPH, July 1 '25)

 

{Excerpt}

[Date of report - Country - Province / Region - District - City - Sex - Age - Condition at time of reporting  - Subtype of virus] 

1) 24/06/2025 - Cambodia - Siem Reap province  - F - 41 - Critical  - H5N1 

2) 29/06/2025 - Cambodia - Siem Reap province  - F - 46 - Stable - H5N1 

3) 29/06/2025 - Cambodia - Siem Reap province  - M - 16 - Stable - H5N1 

4) 30/06/2025 - Cambodia - Takeo province - M - 19 months  - Deceased - H5N1 

(...)

Source: Centre for Health Protection, Hong Kong PRC SAR, https://www.chp.gov.hk/files/pdf/2025_avian_influenza_report_vol21_wk26.pdf

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#Monkeypox virus spreads from #cell-to-cell and leads to #neuronal #death in human neural #organoids

Abstract

In 2022-23, the world witnessed the largest recorded outbreak of monkeypox virus (MPXV). Neurological manifestations were reported alongside the detection of MPXV DNA and MPXV-specific antibodies in the cerebrospinal fluid of patients. Here, we analyze the susceptibility of neural tissue to MPXV using human neural organoids (hNOs) exposed to a clade IIb isolate. We report susceptibility of several cell types to the virus, including neural progenitor cells and neurons. The virus efficiently replicates in hNOs, as indicated by the exponential increase of infectious viral titers and establishment of viral factories. Our findings reveal focal enrichment of viral antigen alongside accumulation of cell-associated infectious virus, suggesting viral cell-to-cell spread. Using an mNeonGreen-expressing recombinant MPXV, we confirm cell-associated virus transmission. We furthermore show the formation of beads in infected neurites, a phenomenon associated with neurodegenerative disorders. Bead appearance precedes neurite-initiated cell death, as confirmed through live-cell imaging. Accordingly, hNO-transcriptome analysis reveals alterations in cellular homeostasis and upregulation of neurodegeneration-associated transcripts, despite scarcity of inflammatory and antiviral responses. Notably, tecovirimat treatment of MPXV-infected hNOs significantly reduces infectious virus loads. Our findings suggest that viral disruption of neuritic transport drives neuronal degeneration, potentially contributing to MPXV neuropathology and revealing targets for therapeutic intervention.

Source: Nature Communications, https://www.nature.com/articles/s41467-025-61134-0

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The Lookout – "All's Well", Winslow Homer (1896)

 

Public Domain.

Source: WikiArt, https://www.wikiart.org/en/winslow-homer/the-lookout-alls-well-1896

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#H5N1 Avian #Influenza: A Narrative #Review of Scientific Advances and #Global #Policy Challenges

Abstract

The H5N1 avian influenza virus continues to evolve into genetically diverse and highly pathogenic clades with increased potential for cross-species transmission. Recent scientific advances have included the development of next-generation vaccine platforms, promising antiviral compounds, and more sensitive diagnostic tools, alongside strengthened surveillance systems in both animals and humans. However, persistent structural challenges hinder global readiness. Vaccine production is heavily concentrated in high-income countries, limiting equitable access during potential pandemics. Economic and logistical barriers complicate the implementation of control strategies such as vaccination, culling, and compensation schemes. Gaps in international coordination, public communication, and standardization of protocols further exacerbate vulnerabilities. Although sustained human-to-human transmission has not been documented, the severity of confirmed infections and the rapid global spread among wildlife and domestic animals underscore the urgent need for robust preparedness. International organizations have called for comprehensive pandemic response plans, enhanced multisectoral collaboration, and investment in targeted research. Priorities include expanding surveillance to asymptomatic animal hosts, evaluating viral shedding and transmission routes, and developing strain-specific and universal vaccines. Strengthening global cooperation and public health infrastructure will be critical to mitigate the growing threat of H5N1 and reduce the risk of a future influenza pandemic.

Source: Viruses, https://www.mdpi.com/1999-4915/17/7/927

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{A family cluster of cases:} #Mother, #son contract #H5N1 #birdflu in #Cambodia

 

PHNOM PENH, June 29 (Xinhua) -- A 46-year-old Cambodian mother and her 16-year-old son have been confirmed positive for H5N1 human avian influenza, bringing the total number of cases to 10 so far this year, the Ministry of Health said in a statement on Sunday.

Both victims live in Lbeuk village of Puok district in northwest Siem Reap province.

"According to queries, there were sick and dead poultry at the patients' home and their neighbors' homes as well as in the village, and the patients had been in contact with sick and dead chickens and cooked them for food," it added.

Health authorities are looking into the source of the infection and are examining any suspected cases or people who have been in contact with the victims in order to prevent an outbreak in the community.

Tamiflu (oseltamivir), an antiviral drug to prevent the bird flu from spreading, was also given out to people who had direct contact with the patients, the statement said.

So far this year, the kingdom recorded 10 human cases of H5N1 bird flu, with five deaths, according to the Ministry of Health. 

Source: Xinhua, https://english.news.cn/asiapacific/20250629/d1fbe0711829482d866c9cbda2bb0a03/c.html

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Detection of clade 2.3.4.4b #H5N1 high pathogenicity avian #influenza virus in a #sheep in #UK, 2025

Abstract

Clade 2.3.4.4b H5N1 high pathogenicity avian influenza virus (HPAIV) continues to pose a significant global threat, affecting wild and domestic avian populations, and mammalian species. In early 2024, H5N1 HPAIV was detected in dairy cattle in the United States of America, where it has continued to circulate, with sporadic detections also reported in other ruminant species. The detection of high viral loads in milk from infected cattle, has resulted in several human infections, underscoring the zoonotic potential of these viruses. In response, several countries have intensified surveillance in non-avian species to evaluate the potential for undetected viral circulation in captive mammals. In Great Britain, bulk milk tank testing of cattle and targeted surveillance of captive mammalian species on an infected premises is undertaken in accordance with the outcome of a rapid risk assessment undertaken to determine the epidemiological links between the poultry and captive mammals. A result of this testing was the first recorded detection of clade 2.3.4.4b H5N1 HPAIV in a sheep in March 2025, identified on an infected poultry premises in Great Britain. An initial seropositive result in a single ewe triggered further investigation, confirming serological positivity across repeated sampling and the presence of viral RNA in milk samples. This detection was confined to a single animal and was likely attributable to proximity to infected poultry and a presumed heavily contaminated environment. The implications of this ruminant detection are discussed in the context of interspecies transmission and surveillance strategies.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.06.27.661969v1

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Phylogenetic and #Mutation #Analysis of #Hemagglutinin Gene from Highly Pathogenic Avian #Influenza Virus #H5 Clade 2.3.4.4b in South #America

Abstract

The Highly Pathogenic Avian Influenza Virus (HPAIV) H5 clade 2.3.4.4b has caused severe outbreaks in domestic and wild birds worldwide since its emergence in 2014, and especially since 2020, with outbreaks in Europe and North America. The introduction of the virus into South America was reported for the first time in Colombia in October 2022, followed by outbreaks in other South American countries affecting poultry, wild birds, mammals, and humans. In this study, a phylogenetic and mutation analysis of the hemagglutinin (HA) gene of HPAIV H5N1 2.3.4.4b viruses isolated in South America was performed to analyze its evolution and its transmission and zoonotic potential. The analysis shows an increase in the viral effective population size between April and June 2022, which was followed by multiple outbreaks of HPAIV H5N1 clade 2.3.4.4b in South America. Moreover, the virus variants evolved from a recent common ancestor estimated to have existed in June 2017. The mean rate of evolution of the HA gene was 6.95 × 10−3 substitutions per site per year, and the sequence analysis of HA identified a mutation (D171N) located at antibody binding sites and viral oligomerization interfaces, with implications for immune response evasion and new host species infection. Additionally, viral strains from South America share the substitutions L104M, T156A, P181S, and V210A, compared to the vaccine strain A/chicken/Ghana/AVL763/2021. Understanding the dynamics of viral evolution and transmission is essential for effective prevention strategies to mitigate future outbreaks.

Source: Viruses, https://www.mdpi.com/1999-4915/17/7/924

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History of Mass Transportation: The FS Aln 442 Diesel Multiple-Unit

Di Giorgio Stagni - http://www.stagniweb.it/foto6.asp?File=tee448&righe=1&inizio=45&InizioI=1&RigheI=100&Col=5, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=96379237

Source: Wikipedia, https://it.wikipedia.org/wiki/Automotrici_FS_ALn_442-448

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#Coronavirus Disease Research #References (by AMEDEO, June 28 '25)

 

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#Influenza and Other Respiratory Viruses Research #References (by AMEDEO, June 28 '25)

 

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   PubMed         Abstract available
   
   

   
   Antiviral Res

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   Biochemistry

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    MMWR Morb Mortal Wkly Rep

11. DIAZ MH, Hersh AL, Olson J, Shah SS, et al
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    PubMed         Abstract available
    
    

    
    PLoS Biol

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Highly Pathogenic Avian #Influenza Virus A #H5N1 subclade 2.3.4.4 b isolated from a European grey #seal (Halichoerus grypus) is highly virulent in #ferrets

 

Abstract

Highly pathogenic avian influenza A viruses subtype H5N1 (HPAIV H5N1), subclade 2.3.4.4b infect multiple avian and mammalian species, posing a potential pandemic risk. Here we describe the outcomes of infection of ferrets with a HPAIV H5N1 virus, isolated from a European grey seal in 2023, compared with an older HPAIV H5N1 (A/Indonesia/05/2005). Overall, infection of ferrets with A/grey seal/Netherlands/302603/2023 caused more rapid mortality than infection of ferrets with A/Indonesia/05/2005. Animals developed severe pneumonia and irreversible hypothermia, associated with high levels of virus replication and histopathological changes in the respiratory tract and peripheral organs. As animal models for severe avian influenza virus infections in humans play a key role in the development of intervention strategies against these infections, these findings highlight the importance of using updated ferret models based on circulating virus strains.

Source: Journal of Infectious Diseases, https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiaf348/8176868

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Seventh #Update on #Developments in #Iran (#War) (#IAEA, June 27 '25)

 

Radiation levels in the Gulf region remain normal following the 12-day conflict that severely damaged several nuclear facilities in Iran, Director General Rafael Mariano Grossi of the International Atomic Energy Agency (IAEA) said today.

Citing regional data reported regularly to the IAEA through the International Radiation Monitoring System (IRMIS), Director General Grossi noted that this 48-nation network would have detected an important radioactive release from any damaged nuclear power reactor.

“From a nuclear safety perspective, Iran’s Bushehr Nuclear Power Plant and the Tehran Research Reactor represented our main concern as any strike affecting those facilities – including their off-site power lines – could have caused a radiological accident with potential consequences in Iran as well as beyond its borders in the case of the Bushehr plant. It did not happen, and the worst nuclear safety scenario was thereby avoided,” Director General Grossi said.

Stressing again that nuclear facilities should never be attacked, he reiterated the IAEA’s current assessment – based on information received from Iran’s Nuclear Regulatory Authority – that this month’s Israeli and U.S. strikes on Iranian nuclear sites would have caused localized radioactive releases inside the impacted facilities and localized toxic effects, but there has been no report of increased off-site radiation levels.

The Director General also emphasised the need for IAEA inspectors to continue their verification activities in Iran, as required under its Comprehensive Safeguards Agreement (CSA) with the Agency.

Source: International Atomic Energy Agency, https://www.iaea.org/newscenter/pressreleases/update-on-developments-in-iran-7

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Production and Immune Response Against #Pandemic #Influenza Candidate #Vaccines as Preparedness Against the Circulating #H5N1 Influenza Viruses

Abstract

Background/Objectives:

H5N1 influenza viruses are spreading worldwide and threaten global public health. Preparedness is necessary to mitigate the worst-case scenario should an H5N1 influenza pandemic occur and justify the development of vaccines against circulating H5N1 viruses of concern. 

Methods: 

The production and characterization of egg-based split and inactivated H5Nx of three distinct monovalent antigens from clades 2.3.4.4b, 2.3.2.1c, and 2.3.4 were performed at an industrial scale. These antigens were formulated and their immune responses, when combined or not with IB160 squalene-based oil-in-water emulsion adjuvant in a rat model, were evaluated in a one- or two-dose immunization schedule. IgG antibodies, hemagglutination inhibitions, and microneutralization titers were measured for vaccine-induced immunity and cross-reactivity. 

Results: 

Three monovalent vaccines from clades 2.3.4.4b, 2.3.2.1c, and 2.3.4 were produced at an industrial scale and characterized. The immune responses against the monovalent vaccines showed a clade-specific antibody response and the need to combine with IB160 adjuvant for a required immune response. 

Conclusions: 

Considering the candidate vaccine viruses (CVVs) with the testing potency reagents available and that the antibody response obtained against the CVVs produced was clade-specific, IDCDC RG-71A is the indicated CVV for the predominant currently circulating H5N1 influenza virus of clade 2.3.4.4b and must be combined with adjuvant to induce a higher and efficacious immune response in a two-dose immunization protocol.

Source: Vaccines (Basel), https://www.mdpi.com/2076-393X/13/6/620

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