#Genetic Characterization of Highly Pathogenic Avian #Influenza #H5N1 Clade 2.3.4.4b, #Antarctica, 2024

Abstract

In 2024, we sequenced highly pathogenic avian influenza virus A(H5N1) clade 2.3.4.4b genomes isolated from 5 brown skuas from James Ross Island, Antarctica. Phylogenetic analysis suggested the virus reached Antarctica through South America. Continued genetic surveillance will be critical to elucidate H5N1 virus transmission dynamics within Antarctica and surrounding areas.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/8/25-0186_article

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#Transmission Dynamics of Highly Pathogenic Avian #Influenza #H5N1 and #H5N6 Viruses in Wild #Birds, South #Korea, 2023–2024

Abstract

We analyzed 15 cases of highly pathogenic avian influenza (HPAI) clade 2.3.4.4b virus infections detected in wild birds in South Korea during September 2023–March 2024. We isolated and sequenced 8 H5N1 and 7 H5N6 viruses. We investigated spatiotemporal transmission dynamics by using a Bayesian discrete trait phylodynamic model that incorporated geographic and host species information. Our source–sink dynamics support introductions of H5N1 viruses from northern Japan to South Korea and subsequent spread through multiple regions in South Korea. The H5N6 viruses were most likely introduced into southwestern South Korea and spread northeastward. Wild waterfowl, especially wild ducks, played a key role in transmission of both H5N1 and H5N6 viruses. Our data showed multiple introductions and extensive spread of HPAI clade 2.3.4.4b viruses and bidirectional transmission between Japan and South Korea. Our results highlight the value of enhanced active surveillance for monitoring HPAI viruses, which can provide insight into preventing future outbreaks.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/8/25-0373_article

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Susceptibility and shedding in Mx1+ and Mx1− female #mice experimentally infected with dairy #cattle #H5N1 #influenza viruses

Summary

Background

Clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) (HPAI H5N1) viruses have spread prolifically in dairy cattle in the US, resulting in dozens of human infections, some without well-established links to animal contacts. Many wild mammals have also been affected, including peridomestic house mice.

Methods

Here, we evaluated susceptibility, tissue tropism, and shedding in female PWK/PhJ and BALB/cJ mice, two laboratory strains derived from house mice that differ in expression of the antiviral restriction factor Mx1. PWK/PhJ mice, which were selected for their natural expression of Mx1, better reflect the antiviral capacity of most wild house mice, whereas BALB/cJ mice lack functional Mx1.

Findings

We found that, regardless of Mx1 expression status, mice are susceptible to infection by dairy cattle HPAI H5N1 viruses, that infection leads to systemic spread to non-respiratory sites, and that infected animals shed virus into the environment via urine. Shed virus remained infectious in urine for at least 24 h at room temperature.

Interpretation

These findings suggest that wild house mice could contribute to HPAI H5N1 environmental contamination and may play a role in transmission to other hosts.

Funding

This work was supported by the National Institute of Allergy and Infectious Diseases Centers of Excellence for Influenza Research and Response (contract 75N93021C00014) and by grants from the Japan Agency for Medical Research and Development (JP25wm0125002, JP253fa627001, and JP24fk0108626, to Y.K.).

Source: EBioMedicine, https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(25)00286-5/fulltext

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Spatiotemporal #reconstruction of the North #American #H5N1 #outbreak reveals successive #lineage #replacements by descendant reassortants

Abstract

The November 2021 introduction of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b into North America triggered a devastating outbreak, affecting more than 180 million domestic birds and spreading to more than 80 wildlife species across Canada and the US. From this outbreak, we have sequenced 2955 complete A(H5N1) viral genomes from samples collected in Canada and, in conjunction with previously published data, performed multifaceted phylodynamic analyses. These analyses reveal extensive diversification of A(H5N1) viruses via reassortment with low-pathogenic avian influenza viruses. We find evidence of repeated ancestral strain replacement by direct descendants, indicative of compounding viral fitness increases. Spatiotemporal modeling identified critical geographic areas facilitating transcontinental spread and demonstrated genotype-specific host dynamics, offering essential data for ongoing control and prevention strategies.

Source: Science Advances, https://www.science.org/doi/10.1126/sciadv.adu4909

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#Wastewater #Parvovirus B19 #Signal Amid Rising #Maternal Cases

Abstract

We report widespread detection of parvovirus B19 in Texas Wastewater using hybrid-capture virome sequencing across 43 sites. Wastewater signal correlated with clinical cases at institutional, county, and state levels and preceded case surges by one month. Full-genome coverage enabled real-time mutation tracking, highlighting wastewater's utility for epidemiologic surveillance.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2025.07.07.25331044v1

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Adjuvanted #influenza #vaccination increases pre-existing #H5N1 cross-reactive #antibodies and overcomes immune imprinting patterns

Abstract

Highly pathogenic H5N1 avian influenza viruses of clade 2.3.4.4b cause sporadic human infections and currently raise concerns about a new influenza pandemic. Heterogeneities in disease severity and outcome have been observed in the past and are currently reported among infected farm workers in the US. These may be attributed to differences in pre-existing H5N1 cross-reactive antibodies. In this study, we characterize H5N1 cross-reactive antibody landscapes in the current population and assess the effect of pH1N1/AS03 and non-adjuvanted seasonal influenza vaccination on H5N1 cross-neutralizing and IgG antibody titers targeting a range of influenza virus-derived antigens. We were able to detect H5N1 cross-neutralizing antibodies using a VSV-based pseudovirus system that correlated well with antibodies inhibiting the spread of authentic H5N1 viruses. Additionally, we found that pH1N1/AS03 vaccination increases H5N1 cross-reactive antibodies significantly, while non-adjuvanted influenza vaccination only had a marginal effect. Furthermore, we could show that immune imprinting causes distinct H5N1 cross-reactive antibody patterns pre-vaccination, that were erased by pH1N1/AS03 vaccination.

Competing Interest Statement

B.M. has received research support from Moderna and consulting fees from Rocketvax AG. A.D. is a member of scientific advisory boards for Bioaster and Sanofi, is a consultant for Boost Biopharma, Botanical solutions and Vaccine Formulation Institute, and has research collaborations with Moderna, GSK and Sanofi. The remaining authors declare that they have no competing interests.

Funding Statement

This project was supported by the Swiss National Science Foundation Ambizione program (grant number: 193475) and a research grant from Moderna Inc. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2025.07.08.25331087v1

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Pathogenicity, #transmissibility, and #receptor #binding of a #human-isolated #influenza A #H10N5 virus

ABSTRACT

Recently, human infections with H10 influenza viruses, including H10N8 and H10N3, have been reported. In January 2024, a case of H10N5 and H3N2 co-infection was reported in Zhejiang Province, China, which is the first human infection with H10N5 avian influenza virus (AIV) globally. Almost simultaneously, we isolated a wild bird-derived H10N5 strain similar to the human H10N5 strain. To assess the public health risk, it is necessary to understand the zoonotic characteristics of these novel H10N5 viruses. Here, we evaluated the biological characteristics of human H10N5, wild bird H10N5, as well as poultry H10N8 in vitro and in vivo. We demonstrate that the novel H10N5 isolates infected and replicated effectively in human lung epithelial cells. They infected BALB/c mice without adaptation, which exhibited robust pathogenicity and caused mouse death. In guinea pig transmission experiments, the H10N5 strain spread through neither direct contact nor airborne exposure, whereas H10N8 transmitted effectively. Additionally, H10N5 exhibited dual receptor-binding characteristics with a stronger preference for avian receptors. The current public health risk of H10N5 is low. However, the occasional spillover infections of H10 AIV into humans and dual receptor-binding characteristics suggest a potential risk of cross-species transmission.

IMPORTANCE

In 2024, the H10N5 AIV was first reported to infect humans. Concurrently, we isolated a strain of H10N5 from wild birds that was highly similar to the human H10N5 strain. However, the zoonotic potential and the associated public health risks of the H10N5 virus remain unclear. In this study, we systematically evaluated the replication characteristics of human H10N5, wild bird H10N5, and poultry H10N8 in human lung epithelial cells, the virulence in mice, the transmission capabilities in guinea pigs, and the receptor-binding properties. Our results demonstrate that these novel H10N5 viruses have not yet acquired the ability to transmit in guinea pigs, but they possess the potential to infect mammals. These findings provide timely insights and warnings for the development of public health prevention strategies.

Source: mBio, https://journals.asm.org/doi/10.1128/mbio.00731-25

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#Phylogenetic analysis of #H5N1 #influenza viruses isolated from dairy #cattle in #Texas in December 2024

LETTER

Highly pathogenic avian influenza (HPAI) viruses of genotype B3.13 were first reported in dairy cattle in March 2024 and, by 4 March 2025, had infected at least 989 cattle herds in 17 states in the US (https://www.aphis.usda.gov/livestock-poultry-disease/avian/avian-influenza/hpai-detections/hpai-confirmed-cases-livestock; accessed on March 24, 2025). Importantly, spillover infections of poultry and mammalian species, including cats and humans, have occurred (https://www.cdc.gov/bird-flu/situation-summary/index.html; accessed on 4 March 2025). Texas reported several infected herds in the spring (1) and early summer of 2024 but saw fewer outbreaks during the second half of 2024, with reported outbreaks in July and December (2). Since September 2024, almost all reported outbreaks of genotype B3.13 viruses in dairy cattle have occurred in California. Here, we characterized self-submitted samples from a farm in Texas that experienced an outbreak in December 2024. This farm had purchased dairy cattle from several states in the US. We, therefore, asked whether the December 2024 outbreak in Texas was caused by B3.13 viruses that circulated undetected in dairy cattle or other species in Texas or resulted from the introduction of B3.13 viruses from California (having the highest number of affected farms at that time) or other states.

(...)

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.00580-25?af=R

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Differential #severity of #SARS-CoV-2 #variant infections in #children and #adults with #COVID19

Highlights

• This study evaluated differences in SARS-CoV-2 variant severity from 2020-2023

• SARS-CoV-2 whole-genome sequencing from 6,916 respiratory swabs was performed

• Four conserved kmer sequences associated with severity were identified

• Infections from the Delta variant had highest likelihood of severe infection

• Omicron BA.4/5 variant was more severe than BA.1 in children, vice-versa in adults

Abstract

We performed virus whole-genome sequencing of 6,916 upper respiratory swabs from adults and children from March 2020 through May 2023 and collected clinical metadata to assess differences in SARS-CoV-2 variant severity and symptomatology. Multivariable logistic regression showed a severity peak with Delta, which had the highest likelihood of severe infection. In children, another peak was observed with BA.4/BA.5, which was associated with more severe infection than both prior (BA.1) and later (BQ.1, BF.7, and XBB) Omicron variants. In contrast, BA.4/BA.5 in adults was associated with less severe infection than BA.1. Genome-wide association studies revealed that nonstructural protein 5 (nsp5, also called 3C-chymotrypsin-like protease), the Paxlovid target, and the spike N-terminal domain were strongly associated with severity. Kmers (contiguous nucleotide sequences of a fixed length k) from these regions matched the prototype Wuhan sequence exactly, corroborating decreases in severity over time. One kmer in the spike gene region was conserved in Delta genomes, with the kmer retained in higher proportions in patients with more severe infection. Our results show, with the exception of Delta, decreased severity associated with SARS-CoV-2 variant infection over time and underscore the potential utility of kmer monitoring to assess variant severity.

Source: Journal of Clinical Virology, https://www.sciencedirect.com/science/article/abs/pii/S1386653225000757?dgcid=rss_sd_all

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Enhancing the #response to avian #influenza in the #US and globally

Summary

The recent emergence of highly pathogenic H5N1 avian influenza virus infections in dairy cows and humans in the U.S. has raised alarms regarding the potential for a pandemic. Over 995 dairy cow herds and at least 70 humans have been affected, including cases of severe disease and the first reported H5N1-related death in the U.S. Sporadic human infections with no known contact with infected animals highlight the possibility of viral adaptation for efficient human-to-human transmission. Concurrently, the virus continues to circulate in wild birds, backyard flocks, and hunted migratory species, further amplifying the risk to humans and domestic animals. This article provides an overview of the current outbreak status, emphasizes the importance of robust surveillance systems to detect emerging strains with pandemic potential, and highlights risks to the U.S. dairy and poultry industries. Recommendations for risk mitigation include enhanced biosecurity measures, improved surveillance, decentralized testing, and targeted public health messaging. The Global Virus Network calls for urgent, proactive measures to prevent widespread outbreaks, leveraging lessons learned from prior pandemics. These measures include targeted vaccination, improved communication strategies to combat vaccine hesitancy, and the incorporation of social sciences to address barriers to public health interventions.

Source: Lancet Regional Health Americas, https://www.thelancet.com/journals/lanam/article/PIIS2667-193X(25)00110-3/fulltext

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Efficacy, immunogenicity, and safety of a next-generation #mRNA-1283 #COVID19 #vaccine compared with mRNA-1273 vaccine (NextCOVE)...

Summary

Background

mRNA-1283 is an investigational, next-generation COVID-19 vaccine that encodes only the immunodominant regions of the SARS-CoV-2 spike protein—the receptor-binding domain (RBD) and the N-terminal domain rather than the full-length spike used in currently authorised mRNA vaccines. We evaluated the relative vaccine efficacy (rVE), immunogenicity, and safety of mRNA-1283 compared to the first-generation vaccine (mRNA-1273).

Methods

This randomised, observer-masked, active-controlled, phase 3 trial (NextCOVE) was conducted in individuals (aged ≥12 years) with no evidence of SARS-CoV-2 infection within 90 days of screening in the USA, the UK, and Canada. Participants were randomly assigned in a 1:1 ratio to receive one 10 μg dose of the bivalent formulation of mRNA-1283 (original plus omicron BA.4/BA.5) or 50 μg of the bivalent mRNA-1273, encoding the same variants. Randomisation was stratified by age (12–17 years, 18–64 years, and ≥65 years). Primary objectives comparing mRNA-1283 with mRNA-1273 were non-inferior rVE to prevent a first event of COVID-19 from 14 days after study injection to the end of follow-up (assessed in the per-protocol set for efficacy, with non-inferiority declared when the lower bound of the α-adjusted two-sided CI for rVE was greater than –10%), non-inferior immunogenicity at day 29 (assessed in the per-protocol immunogenicity subset, with non-inferiority declared when the lower bounds of the CIs for the geometric mean concentration ratios [GMRs] of neutralising antibodies against SARS-CoV-2 D614G and omicron BA.4/BA.5 were >0·667 and the lower bounds of the 95% CI seroresponse rate differences for the two variants were greater than –10%), and safety (assessed in the safety set, which included all participants who received a vaccination). The trial is registered at ClinicalTrials.gov (NCT05815498) and is complete.

Findings

Between March 28 and Aug 23, 2023, we screened 13 054 individuals for eligibility and randomly allocated 11 454 participants (5728 to mRNA-1283 and 5726 to mRNA-1273). 1177 confirmed COVID-19 events occurred up to Jan 31, 2024 (560 [9·9%] of 5679 in mRNA1283.222 and 617 [10·8%] of 5687 in mRNA-1273.222). The median age of participants at enrolment was 56 years (IQR 38–66). Of the 11 417 participants who received a vaccine, 6200 (54·3%) were female and 5217 (45·7%) were male; 9381 (82·2%) were White; and 1510 (13·2%) were Hispanic or Latino. Of the total cohort, 992 (8·7%) participants were aged 12–17 years, 7151 (62·6%) were aged 18–64 years, and 3274 (28·7%) were 65 years and older; in addition, 6857 participants (60·1%) were 50 years and older. The rVE point estimate was 9·3% (99·4% CI –6·6 to 22·8; p=0·0005). The GMR was 1·3 (95% CI 1·2 to 1·5) for BA.4/BA.5 and 1·2 (1·1 to 1·4) for D614G. The day-29 seroresponse rate difference was 14·4% (95% CI 9·3 to 19·4) for BA.4/BA.5 and 10·7% (6·0 to 15·4) for D614G. Local and systemic adverse reactions were similar between mRNA-1283 and mRNA-1273; mRNA-1283 was associated with fewer injection-site pain reactions than mRNA-1273 (3905 [68·5%] of 5701 vs 4419 [77·5%] of 5705, respectively). The frequency of unsolicited adverse events, serious adverse events, and medically attended adverse events were similar between groups during the first 28 days after injection. One event of sudden death occurred in a participant with underlying cardiovascular disease in the mRNA-1273 group; it was reported as related to vaccination due to its temporal association.

Interpretation

mRNA-1283 was well-tolerated. The rVE and immunogenicity non-inferiority criteria were met, with higher antibody responses for mRNA-1283 versus mRNA-1273. The potential clinical benefit of mRNA-1283 versus mRNA-1273 needs to be confirmed in post-marketing evaluation.

Funding

Moderna.

Source: The Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00236-1/fulltext?rss=yes

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Predictive #models of #influenza A virus #lethal disease yield insights from #ferret respiratory tract and #brain tissues

Abstract

Collection of systemic tissues from influenza A virus (IAV)-infected ferrets at a fixed timepoint post-inoculation represents a frequent component of risk assessment activities to assess the capacity of IAV to replicate systemically. However, few studies have evaluated how the frequency and magnitude of IAV replication at discrete tissues contribute to within-host phenotypic outcomes, limiting our ability to fully contextualize results from scheduled necropsy into risk assessment settings. Employing aggregated data from ferrets inoculated with > 100 unique IAV (both human- and avian-origin viruses, spanning H1, H2, H3, H5, H7, and H9 subtypes), we examined relationships between infectious virus detection in four discrete tissue types (nasal turbinate, lung, brain, and olfactory bulb [BnOB]) to clinical outcomes of IAV-inoculated ferrets, and the utility of including these discrete tissue data as features in machine learning (ML) models. We found that addition of viral tissue titer data maintained high performance metrics of a predictive lethality classification ML model with or without inclusion of serially-collected virological and clinical data. Interestingly, infectious virus in BnOB was detected at higher frequency and magnitude among IAV associated with high pathogenicity phenotypes in ferrets, more so than tissues from the respiratory tract; in agreement, BnOB was the highest relative ranked individual tissue specimen in predictive classification models. This study highlights the potential role of BnOB viral titers in assessing IAV pathogenicity in ferrets, and highlights the role ML approaches can contribute towards understanding the predictive benefit of in vivo-generated data in the context of pandemic risk assessment.

Source: Scientific Reports, https://www.nature.com/articles/s41598-025-09154-0

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Vertical #Transmission of #Bovine #H5N1 during #Pregnancy and #Lactation in #Mice

Abstract

Panzootic spillover of H5N1 virus clade 2.3.4.4b has resulted in expanded host range among placental mammals, with lactation transmission via milk documented. Whether infection during pregnancy leads to in utero or lactational vertical transmission remains unknown. Pregnant outbred mice were infected with A/bovine/Ohio/B24OSU-472/2024 during the second or third trimester equivalent. Second trimester infection caused in utero infection, with infectious virus detected in the uterus, placenta, and fetus. Birth following third trimester infection resulted in offspring with decreased size and neurodevelopmental delays, with infectious virus detected in the neonatal milk ring and lungs as well as mammary tissues. Ongoing H5N1 infections present increased risk for human exposure and an H5N1 vertical transmission model in placental mammals is essential for understanding viral spread and evaluating treatments during pregnancy.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.07.07.663583v1

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The #spread of highly pathogenic avian #influenza virus is a #social #network problem

Abstract

Despite identification of Highly Pathogenic Avian Influenza viruses nearly 75 years ago, the transmission pathways among wild animals remain incompletely described. We propose the use of social networks, to complement phylodynamic modeling, for better surveillance, prediction, and prioritization of HPAI.

Source: PLoS Pathogens, https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1013233

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#Wastewater #Data for Avian #Influenza A(#H5) (#US CDC, July 7 '25)

 

{Excerpt}

Time Period: June 22, 2025 - June 28, 2025

-- H5 Detection: 3 sites (0.8%)

-- No Detection: 370 sites (99.2%)

-- No samples in last week: 52 sites

(...)

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/nwss/rv/wwd-h5.html

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#Finland - #Influenza A #H5N5 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

By © Giles Laurent, gileslaurent.com, License CC BY-SA, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=142133890

 A wild Golden Eagle in Lapin aluehallintovirasto Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6597

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#Norway - #Influenza A #H5 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 

By Andreas Trepte - Own work, CC BY-SA 2.5, https://commons.wikimedia.org/w/index.php?curid=10944563

A Great black-backed Gull in Nordland Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6594

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Detection of a Novel #Gull-like Clade of Newcastle Disease Virus and #H3N8 Avian #Influenza Virus in the #Arctic Region of #Russia (Taimyr Peninsula)

Abstract

Wild waterbirds are circulating important RNA viruses, such as avian coronaviruses, avian astroviruses, avian influenza viruses, and avian paramyxoviruses. Waterbird migration routes cover vast territories both within and between continents. The breeding grounds of many species are in the Arctic, but research into this region is rare. This study reports the first Newcastle disease virus (NDV) detection in Arctic Russia. As a result of a five-year study (from 2019 to 2023) of avian paramyxoviruses and avian influenza viruses in wild waterbirds of the Taimyr Peninsula, whole-genome sequences of NDV and H3N8 were obtained. The resulting influenza virus isolate was phylogenetically related to viruses that circulated between 2021 and 2023 in Eurasia, Siberia, and Asia. All NDV sequences were obtained from the Herring gull, and other gull sequences formed a separate gull-like clade in the sub-genotype I.1.2.1, Class II. This may indirectly indicate that different NDV variants adapt to more host species than is commonly believed. Further surveillance of other gull species may help to test the hypothesis of putative gull-specific NDV lineage and better understand their role in the evolution and global spread of NDV.

Source: Viruses, https://www.mdpi.com/1999-4915/17/7/955

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Highly pathogenic avian #influenza #H5N1 in the #USA: recent incursions and #spillover to #cattle

Abstract

Since Spring 2024, new genotypes of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b have been identified in the United States (US). These HPAI H5N1 genotypes have caused unprecedented multi-state outbreaks in poultry and dairy farms, and human infections. Here, we discuss the current situation of this outbreak and emphasizes the need for pre-pandemic preparedness to control HPAI H5N1 in both poultry and dairy farms in the US.

Source: npj Viruses, https://www.nature.com/articles/s44298-025-00138-5

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#H5N1 virus invades the mammary #glands of dairy #cattle through “mouth-to-teat” #transmission

Abstract

H5N1 influenza outbreaks have been reported on more than 1,070 dairy farms across 17 states in the US. Damage to the mammary gland and high levels of virus in milk were common features of the infected cattle, but it is unclear how the virus initially invades the mammary glands, and no control strategy is currently available. Here, we found that cattle oral tissues support H5N1 virus binding and replication, and virus replicating in the mouth of cattle transmitted to the mammary glands of dairy cattle during sucking. We also found that an H5 inactivated vaccine or a hemagglutinin-based DNA vaccine induced sterilizing immunity in cows against challenges with different H5N1 viruses. Our study provides insights into H5N1 virus transmission and control in cattle.

Source: National Science Review, https://academic.oup.com/nsr/advance-article/doi/10.1093/nsr/nwaf262/8180392?searchresult=1

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