Receptors in mammary glands make livestock and humans inviting hosts for avian flu

Iowa State University

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Microscope-captured images of a mammary gland of a pig show the presence of influenza receptors. In the image on the left, receptors for avian influenza A are colored orange. In the image on the right, receptors for the type of influenza A that typically infects mammals are purple.

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Credit: Tyler Harm/Iowa State University.

AMES, Iowa – An ongoing outbreak of highly pathogenic avian influenza has affected more than 184 million domestic poultry since 2022 and, since making the leap to dairy cattle in spring 2024, more than 1,000 milking cow herds.

A new study led by Iowa State University researchers shows that the mammary glands of several other production animals – including pigs, sheep, goats, beef cattle and alpacas – are biologically suitable to harbor avian influenza, due to high levels of sialic acids.

“The main thing we wanted to understand in this study is whether there is potential for transmission among these other domestic mammals and humans, and it looks like there is,” said Rahul Nelli, the study’s lead author and a research assistant professor of veterinary diagnostic and production animal medicine.

Sialic acid, a sugar molecule found on the surface of many types of animal cells, provides an influenza virus the microscopic docking station it needs to infect a host cell, an entry point for attaching and invading. A study by many of the same researchers last year found that dairy cattle udders have high levels of sialic acid, which helped explain why the H5N1 avian influenza outbreak was able to spread rapidly among dairy herds.

In the study published Nov. 27 in the Journal of Dairy Science, a research team that includes scientists from the ISU College of Veterinary Medicine and the U.S. Department of Agriculture’s National Animal Disease Center in Ames also found the same receptors in the mammary glands of the humans.

Only a few sporadic cases of H5N1 infection have been reported in the animals examined in the new study, but those species aren’t being tested on a widespread basis, said Dr. Todd Bell, professor of veterinary pathology and a study co-author.

“If we don’t look, we don’t know,” Bell said.

In dairy herds, H5N1 infections are causing sick cows to produce milk contaminated with the virus, prompting nationwide surveillance testing of raw cow milk samples by the USDA. Pasteurization kills influenza viruses, so store-bought milk is safe. But concerns about raw milk should extend to other mammalian livestock, Nelli said.

“Some people do consume the raw milk of these other animals,” he said.

The presence of the virus in milk from infected cows has likely played a role in the H5N1 spreading and makes transmission to humans a bigger risk, Nelli said.

“If a virus in livestock is being spread by respiratory infections, few humans will be in close enough contact to catch it. But milk is an entirely different situation because it’s transported into communities,” he said. 

All of the mammary gland tissues examined in the new study had sialic acid receptors preferred by both avian influenza and the seasonal influenza that circulates more readily among humans. The possibility of both types of viruses comingling and transmitting between different species heightens concerns about more dangerous adaptations emerging, Bell said. H5N1 has in the past had a fatality rate in humans of around 50%, though the 71 confirmed human infections during the current outbreak have led to just two deaths.

“We need to try to stay ahead of this so it doesn’t have a chance to continue to replicate and potentially evolve into something even more troublesome,” he said.

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Journal

Journal of Dairy Science

DOI

10.3168/jds.2025-26950 

Method of Research

Observational study

Subject of Research

Animals

Article Title

Exploring influenza A virus receptor distribution in the lactating mammary gland of domesticated livestock and in human breast tissue

 

Avian Flu, from ‘FluWarning’ early alerts for virus spillovers

A system developed by Researchers at the Politecnico di Milano and the University of Milan detects changes that may indicate cross-species transmission and anticipate possible epidemics

Politecnico di Milano

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Reassortant virus

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Credit: Politecnico di Milano

How can we monitor the cross-species transmission of avian flu? The answer is FluWarning, a digital system that reports abnormal changes in flu viruses, developed by a research team from the Politecnico di Milano and the University of Milan. The system analyses the genetic code of flu viruses, looking for subtle but significant changes that could indicate cross-species transmission (for example, from birds to cattle or to humans), a process known as spillover.

The study, which was recently published in the prestigious journal Science Advances, was developed under the NRRP-funded PRIN 2022 – SENSIBLE project (Small-data Early warNing System for viral pathogens In puBLic hEalth). The FluWarning research team includes three members from DEIB – Department of Electronics, Information and Bioengineering at the Politecnico di Milano, SENSIBLE’s Principal Investigator Anna Bernasconi, Professor Stefano Ceri and Researcher Tommaso Alfonsi, along with Matteo Chiara, Professor in the Department of Biosciences at the University of Milan.

The study relied on data from GISAID, a platform for sharing virus sequences and the related metadata produced by laboratories all around the world. FluWarning was developed using data from the H1N1 swine flu pandemic in 2009, a well-documented example of a virus being transmitted from animals to humans. It was then applied to H5N1 bird flu, a highly pathogenic strain among birds, which in the past year has also begun to spread among US cattle.

The system uses a statistical method to recognise anomalies. Depending on the settings, it can be used to recognise individual anomalous sequences or groups of anomalous sequences. FluWarning learns the normal sequences of influenza viruses and issues an alert whenever the code of the sequences changes significantly. For each alert, virologists analyse the corresponding sequences and confirm or reject the presence of spillover.

‘With its simple installation and analysis that can be done for specific locations and over specific time periods, the FluWarning software can potentially be used by many laboratories or regional genomic surveillance institutions, enabling important discoveries on both small and large scales,’ Anna Bernasconi notes. ‘In fact, the system is perfectly operational. It can give feedback on these changes day by day.’

In 2024–2025, two H5N1 genotypes were linked to independent outbreaks in the US, where numerous heads of dairy cattle were found to be infected with bird flu. ‘FluWarning identified clusters of viral activity in several US states, particularly in California, where a state of emergency was declared on 18 December 2024 due to the risk of bird flu contamination in cattle. Surprisingly, some FluWarning alerts appeared before official reports were published. The system also detected specific mutations in the haemagglutinin (HA) gene, a key protein that affects the way the virus infects the host cells,’ Matteo Chiara says. The tool monitored the evolution of the virus and identified characteristic markers of the California strains.

‘FluWarning is an important step towards more effective detection of viral changes that could pose a risk to animals or humans. By making this technology widely available, we hope to strengthen global surveillance on a health issue of global significance’ Stefano Ceri concludes.

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Journal

Science Advances

DOI

10.1126/sciadv.adz7312 

Method of Research

Data/statistical analysis

Subject of Research

Not applicable

Article Title

Lightweight multiscale early warning system for influenza A spillovers

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ZOONOSIS

France raises bird flu alert to highest level after new outbreaks

France raised its bird flu alert to the highest level on Wednesday after a rise in new cases in poultry and backyard flocks, triggering stricter biosecurity rules including the confinement of birds.


Issued on: 22/10/2025 - RFI

France has raised its bird flu alert to the highest level following new outbreaks in poultry and wild birds. AP - Bob Edme

A government decree in the Journal officiel confirmed the risk level will move from “moderate” to “high”, the top tier in the national alert system.

The move means poultry must now be sheltered and protected from contact with wild birds – an early precaution compared with previous years.

Authorities said the decision was prompted by “the dynamic spread of highly pathogenic avian influenza (HPAI) in migratory flyways crossing France”, with new cases detected among migratory wild birds on French territory.

Officials warned these birds could pass the virus to domestic flocks.

In just 10 days, five outbreaks of HPAI have been confirmed across the country – two on commercial poultry farms and three in smaller backyard holdings. The new decree aims to “reinforce surveillance and prevention measures” to limit further spread.

Hundreds of geese slaughtered as bird flu grips France's Dordogne

Early warning

France classifies bird flu risk in three categories – negligible, moderate and high. The level had remained “negligible” since May before being raised to “moderate” last week.

This year’s shift to the highest alert comes earlier than usual. In previous seasons, it was typically activated in November or December.

Under the “high risk” designation, birds must be sheltered indoors or protected by nets. On larger farms with more than 50 birds, feeding and watering systems must also be covered to prevent contamination from wild species.

Smaller flocks must be either confined or kept under netting.

Since October 2023, France has slightly eased certain confinement rules to ease the strain on free-range producers.

Poultry farmers raising chickens and guinea fowl can, from eight weeks of age, and turkeys from 10 weeks, let their birds outside – but only in restricted areas and without needing prior approval from local authorities.

Laying hens kept outdoors may also continue to roam within a reduced enclosure, provided farmers obtain the green light from their regional prefecture.

Europe in midst of worst ever bird flu outbreak, authorities warn

A Europe-wide concern

According to the European health surveillance platform ESA, 37 outbreaks of avian influenza were reported in poultry holdings across the EU between 1 August and 12 October, with additional cases since then – including several in France.

While the jump to “high risk” status will add new constraints for French farmers, officials hope early action will prevent a repeat of the devastating waves of bird flu seen in recent years.

With tighter monitoring and earlier containment, authorities aim to keep both flocks and consumers safe as migratory birds begin their autumn journeys.

(with newswires)

Taiwan detects first cases of swine fever

Taipei (AFP) – Taiwan has culled dozens of pigs after detecting its first cases of African swine fever, with the agriculture ministry saying Thursday no other infections have been detected elsewhere on the island.


Issued on: 23/10/2025 - FRANCE24

A vendor cuts meat at a pork stall at a local traditional market in Keelung. Taiwan has culled dozens of pigs after detecting its first cases of African swine fever © I-Hwa Cheng / AFP

The virus -- which does not affect humans -- is highly contagious and fatal for pigs, and an outbreak is potentially devastating for the pork industry, experts say.

"No abnormalities have been observed (elsewhere) so far," Deputy Agriculture Minister Tu Wen-jane told a news conference in the central city of Taichung where the infections were detected.

Samples of dead pigs at a farm in Wuqi district tested positive for swine fever this month and 195 pigs were culled, the ministry said Wednesday.

Taichung authorities were tracing the whereabouts of 28 pigs from the farm that were sold in markets, Lin Nien-nung, from the ministry's Animal and Plant Health Inspection Agency, said Thursday.

The ministry said a three-kilometre (nearly two-mile) "control zone" was set up to prevent the infection from spreading, while the transport and slaughter of pigs across the island is banned for five days.

Taiwan has around five million pigs and the pork industry generates about NT$70 billion (US$2.3 billion) a year, official data show.

President Lai Ching-te has urged the public to "not panic" and called on local governments, livestock associations and pig farmers to be "highly vigilant".

"If any abnormal deaths or suspected animal infections are found among pigs, please immediately report them to the local animal quarantine authorities," Lai said in a Facebook post.

© 2025 AFP

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A ‘universal’ therapy against the seasonal flu? Antibody cocktail targets virus weak spot

Unusual immune strategy protects against all tested flu strains and prevents viral escape

Jackson Laboratory

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An unusual therapy developed at The Jackson Laboratory (JAX) could change the way the world fights influenza, one of the deadliest infectious diseases.

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Credit: The Jackson Laboratory

An unusual therapy developed at The Jackson Laboratory (JAX) could change the way the world fights influenza, one of the deadliest infectious diseases. In a new study in Science Advances, researchers report that a cocktail of antibodies protected mice—including those with weakened immune systems—from nearly every strain of influenza tested, including avian and swine variants that pose pandemic threats.

Unlike current FDA-approved flu treatments, which target viral enzymes and can quickly become useless as the virus mutates, this therapy did not allow viral escape, even after a month of repeated exposure in animals. That difference could prove crucial in future outbreaks, when survival often depends on how quickly and effectively doctors can deploy treatments and vaccine development will take about six months.

“This is the first time we’ve seen such broad and lasting protection against flu in a living system,” said Silke Paust, an immunologist at JAX and senior author of the study. “Even when we gave the therapy days after infection most of the treated mice survived.”

The insights challenge a long-held belief that for antibodies to be useful as a therapy against viruses they must be “neutralizing” antibodies that bind directly to viruses and block them from infecting cells. Instead, the team engineered “non-neutralizing” antibodies, which don’t prevent infection but tag infected lung cells and recruit the body’s immune system to clear the infection. This new approach could reshape how scientists design treatments for other viruses.

“The majority of antibodies our bodies make are non-neutralizing, but medicine has largely ignored them,” Paust explained. “We show they can be lifesaving. Even with lethal strains like H5 and H7 avian flu, this therapy saved lives long after infection had taken hold.”

The team focused on a small, highly conserved region of the influenza A virus’s Matrix Protein 2, called M2e. This part of the virus is essential for its life cycle and remains nearly unchanged across infected cells in all flu strains, including human, avian, and swine variants.

The therapy did not lead to viral resistance even after repeated exposure, and sequencing confirmed no mutations in the virus’s M2 region after 24 days of treatment. While the team tested the efficacy of the three antibodies individually, the success came from combining them, as this approach reduces the virus’ chances of escaping three different antibodies.

“The virus didn’t mutate away even when using individual antibodies,” Paust said. “But in a flu season with millions of people taking this therapy, I would be much more confident that we can prevent escape from the therapy if we use the cocktail.”

Paust and her team found that the antibodies were effective at low doses, both before and after influenza infection. The cocktail significantly reduced disease severity and viral load in lungs, and improved survival rates in both healthy and immunocompromised mice.

When testing H7N9, a type of bird flu that can be deadly to both animals and people, the team found that just one dose of the treatment reduced the amount of virus in the lungs, even when it was given four days after infection. The reduced viral loads correlated with better survival rates. All mice survived when treated with the antibody cocktail on the first three days after infection, while 70% and 60% survived on days four and five, respectively.

“We can use very low doses, which is also promising because potential therapies could be cheaper and less likely to produce adverse side effects in people,” Paust said.

While the results are preliminary, they are promising for a future where patients could have access to stockpiled therapeutics to be deployed rapidly to fight seasonal outbreaks or pandemics. Currently, flu vaccines are updated seasonally because the virus continuously mutates, making immunity to prior strains irrelevant.

“We need something that is off the shelf when we don’t necessarily have the time to make a new vaccine if we do have an outbreak or pandemic where lethality is high, so this type of therapy could be readily available for anyone in any situation,” Paust said.

The team is working on designing antibodies for clinical trials. The idea is to make a “humanized” antibody with the same specificity to target the M2 protein, but without triggering an immune response against the therapy itself or diminishing its efficacy in humans. The team envisions a future where the cocktail could work as a standalone prophylactic for elderly, immunocompromised, and other high-risk groups, in addition to serving as a therapy for those severely ill with flu.

Other authors are Teha Kim of The Jackson Laboratory; Lynn Bimler and Amber Y. Song of Baylor College of Medicine; Sydney L. Ronzulli, Scott K. Johnson, Cheryl A. Jones, and S. Mark Tompkins of the Center for Influenza Disease & Emergence Research and the Center for Vaccines and Immunology, University of Georgia.

This research was supported by The Albert and Margaret Alkek Foundation, the National Institutes of Health (grant R01AI130065), and the National Institute of General Medical Sciences of the National Institutes of Health (grant AI053831).

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Journal

Science Advances

DOI

10.1126/sciadv.adx3505s 

Method of Research

Experimental study

Subject of Research

Animals

Article Title

Non-Neutralizing Antibodies to Influenza A Matrix Protein 2 Ectodomain Are Broadly Effective and Resistant to Viral Escape Mutations

Article Publication Date

10-Sep-2025

 

Promising bird flu vaccine advances; organoids reveal how H5N1 scars airways

Texas Biomed researchers are advancing bird flu vaccine candidates and identifying potential treatment targets with mini 3D models of human airways.

Texas Biomedical Research Institute

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A human airway organoid under a light microscope in the labs at Texas Biomed. The organoids have grown cilia, which are fine, hair-like structures that line the interior of the airway. Here, their movements appear like short flashes of light. A molecule is being moved along by the cilia, much like it would in the human body.

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Credit: Texas Biomed

Bird flu vaccine candidate highly effective in early studies

Researchers at Texas Biomedical Research Institute have developed a new, proof-of-concept vaccine to protect people from the bird flu strain currently circulating in the United States. The team, led by Professor Luis Martinez-Sobrido, Ph.D. and Staff Scientist Ahmed M. Elsayed, Ph.D., recently published initial results in npj Vaccines.

The live attenuated vaccine contains a weakened, or attenuated, version of the avian influenza virus that has sickened poultry and dairy cows throughout the U.S. since March 2024. The vaccine candidate showed high efficacy in cells and animal models. A single dose was enough to protect mice from highly pathogenic H5N1, which would otherwise be lethal.

The team is now working to develop versions of the vaccine that would address other bird flu strains circulating in hot spots around the world. Highly pathogenic avian influenza is naturally carried by migratory birds and waterfowl, but is deadly in domesticated chickens and turkeys.

“The ultimate aim is to develop a vaccine that could protect against multiple strains of bird flu, or even offer universal protection,” Dr. Elsayed said.

H5N1 has spread to a wide range of mammal species, from sea lions to cats and now dairy cattle. The current outbreak has sickened more than 70 people in the U.S. and killed at least one person to date, primarily through contact with infected livestock. Many experts are concerned the virus could evolve to spread between people, causing a more severe pandemic. The U.S. has emergency stockpiles of bird flu vaccines available, which are based on inactivated, or killed, versions of older bird flu viruses.

“Those vaccines have shown to work against the current strain of H5N1,” Dr. Martinez-Sobrido said. “However, live attenuated vaccines can offer longer-lasting and more robust protection.”

This research was funded through a pilot grant provided to Dr. Elsayed by the Texas Biomedical Forum, a philanthropic women’s organization dedicated to supporting Texas Biomed.

Organoids show how bird flu affects airway cells, reveal potential treatment target

The current strain of H5N1 bird flu circulating in the U.S. remodels the cells lining the human airway, causing scar tissue to form, researchers at Texas Biomed report in Emerging Microbes & Infections. Dr. Martinez-Sobrido and his team, led by Staff Scientist Hussin Rothan, Ph.D., identified a potential treatment target to reduce harmful inflammation associated with influenza infection.

The researchers used human airway organoids for this project. Organoids are miniature 3D models of specific tissues and have been developed in labs around the world for decades. These human airway organoids contain four critical cell types found in the trachea and they mimic the physical structure of the airway lining, or epithelium.

“They create mucus and you can see the cilia moving under the microscope,” said Dr. Rothan. “We can get much more detailed insight into tissue responses from these organoids than we can from single cell lines.”

When exposed to a version of the bird flu first detected in Texas dairy cattle last spring, the organoids showed significant inflammatory responses, including increased production of cytokine proteins, and the development of fibrotic, or scar, tissue. The inflammatory response was far more severe for H5N1 compared to infection with a seasonal swine flu strain, H1N1.

The team found that briefly inhibiting a key driver of inflammation, known as the ROCK pathway, helped reduce the scarring. Specifically, they found that inhibiting the enzyme ROCK1 was more effective than inhibiting another enzyme, ROCK2.

“This was surprising because people usually focus on ROCK2,” Dr. Rothan said. “We now need to drill down and find out more about these interactions so we can find the most effective way to limit inflammation, not only for bird flu, but other respiratory viruses that affect the airway and lungs like SARS-CoV-2.”

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About Texas Biomed

Texas Biomed is a nonprofit research institute dedicated to protecting the global community from infectious diseases. Through basic research, preclinical testing and innovative partnerships, we accelerate diagnostics, therapies and vaccines for the world’s deadliest pathogens. Our San Antonio campus hosts high containment laboratories and the Southwest National Primate Research Center. Our scientists collaborate with industry and researchers globally, and have helped deliver the first COVID-19 vaccine, the first Ebola treatment and first Hepatitis C therapy.

Papers:

Mostafa, A., Ye, C., Barre, R.S. et al. A live attenuated NS1-deficient vaccine candidate for cattle-origin influenza A (H5N1) clade 2.3.4.4.b viruses. npj Vaccines 10, 151 (2025). https://doi.org/10.1038/s41541-025-01207-9

Rothan, Hussin, Ahmed Mostafa, Mahmoud Bayoumi, Chengjin Ye, Ramya S. Barre, Anna Allué-Guardia, Aitor Nogales, Jordi B. Torrelles, and Luis Martinez-Sobrido. 2025. “Emerging Highly Pathogenic H5N1 Influenza Triggers Fibrotic Remodeling in Human Airway Organoids.” Emerging Microbes & Infections 14 (1). doi:10.1080/22221751.2025.2532684.

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Journal

npj Vaccines

DOI

10.1038/s41541-025-01207-9 

Article Title

A live attenuated NS1-deficient vaccine candidate for cattle-origin influenza A (H5N1) clade 2.3.4.4.b viruses