Pfizer/BioNTechs Omicron JN.1-adapted COVID-19 vaccine has been approved for use by the Medicines and Healthcare products Regulatory Agency (MHRA) for adults and children from infancy.
Four versions of the adapted Comirnaty JN.1 vaccine have been approved by the UK regulator under the International Recognition Procedure after meeting the standards of safety, quality and effectiveness.
Both the Comirnaty JN.1 30mg dose for injection and in a pre-filled syringe have been approved for use in adults, while 10mg for single-dose vial injection has been approved for use in children aged five to 11 years of age and 3mg for three-dose vial injection has been authorised for infants and children from six months to four years of age.
The vaccine is designed to trigger the production of antibodies and blood cells by the immune system to work against COVID-19, an infectious disease caused by the SARS-CoV-2 virus, following the recommendation from the World Health Organizations Technical Advisory Group and the European Medicines Agencys (EMA) Emergency Task Force to update COVID-19 vaccines to target the JN.1 variant the most widely circulating variant worldwide, which continues to grow quickly compared to other variants and is either more transmissible or better at evading the immune system.
The approval was based on positive results and real-world evidence supporting the safety and efficacy of the Comirnaty vaccines, which showed that the JN.1-adapted vaccine generated a substantially improved response against several Omicron JN.1 sublineages, including KP.2, KP.3, as well as other currently circulating sublineages, in comparison to the companies Omicron XBB.1.5-adapted monovalent COVID-19 vaccine.
The approval comes after the EMAs human medicine committee recommended the Omicron JN.1-adapted monovalent COVID-19 vaccine for individuals aged six months and older.
Previously, in February, the MHRA approved a change to the licence of the Comirnaty Omicron XBB.1.5-adapted COVID-19 vaccine following approval from the UK regulator in September 2023 for use in individuals aged six months and older.
Additionally, in October 2023, the companies announced positive results from an ongoing phase 1/2 study of their mRNA-based combination vaccine for influenza and COVID-19, as well as outlined plans to enter late-stage development.
The initiative is being led by Argentinian manufacturer Sinergium Biotech.
July 29, 2024, 3:00 PM ET
4 min read
The World Health Organization announced Monday that it has launched an initiative to help accelerate the development of a human bird flu vaccine using messenger RNA (mRNA) technology.
The project, which will be led by Argentinian pharmaceutical company Sinergium Biotech, will aim to identify vaccine candidates for manufacturers in low- and middle-income countries, the WHO said.
The Centers for Disease Control and Prevention (CDC) has previously said the risk of bird flu, also known as avian influenza, to the general public is low and there is currently no evidence of human-to-human transmission. Federal health officials have also prepared millions of vials of an available non-mRNA bird flu vaccine as a precautionary measure, just in case it becomes necessary.
mRNA technology is the same type that was used in the development of COVID vaccines. Most vaccines use a weakened or inactive virus to stimulate an immune response, but mRNA vaccines teach the body how to make proteins that can trigger an immune response and fight off an infection.
Researchers can often design mRNA vaccines more quickly than they can produce the live or weakened pathogens needed for a traditional vaccine.
The initiative is part of the WHO's mRNA Technology Transfer Program, which has a goal of building capacity in low- and middle-income countries to produce mRNA vaccines.
Sinergium Biotech has already developed candidates for H5N1 vaccines, according to the WHO. The company is looking to perform proof-of-concept studies, in which researchers decide whether to continue studying the product based on its efficacy.
If the proof-of-concept study is successful, Sinergium said it plans to share the "technology, materials and expertise" with other manufacturing partners so they can develop the vaccine themselves.
"This initiative exemplifies why WHO established the mRNA Technology Transfer Programme -- to foster greater research, development and production in low- and middle-income countries, so that when the next pandemic arrives, the world will be better prepared to mount a more effective and more equitable response," WHO Director-General Dr. Tedros Adhanom Ghebreyesus said in a statement.
The WHO says that avian influenza viruses are a "significant public health risk" because they spread widely in animals and have the potential to cause a future pandemic. However, the global health agency indicated that its preparedness efforts are an example of being proactive, rather than reactive, by increasing access to vaccines.
In the United States, there have been 13 human cases of bird flu since April of this year, according to an update last week from the CDC. All the human patients either came into contact with sick dairy cows or infected poultry, according to the CDC.
The U.S. government has also awarded Moderna $176 million to develop and test an mRNA vaccine that could be used for bird flu, Reuters reported in early July.
Monday, the World Health Organization (WHO) unveiled an important new initiative aimed at accelerating the development and accessibility of messenger RNA (mRNA) vaccines for human avian influenza (H5N1) in low- and middle-income countries.
The initiative will be led by Sinergium Biotech, a company based in Argentina, which has committed to sharing its expertise in manufacturing mRNA vaccines for avian influenza with the WHO's Technology Transfer Hub. This collaboration is expected to facilitate the rapid and affordable production of the vaccine for developing nations, according to the WHO.
The mRNA Technology Transfer Hub program involves manufacturers in 15 countries, although not all are fully operational. Participants in the program include Biovac in South Africa and Institut Pasteur in Senegal. Notably, the South African facility was established after major pharmaceutical companies such as Moderna and Pfizer declined to share the technical knowledge required to replicate their COVID vaccines due to intellectual property concerns.
Sinergium has already developed candidate H5N1 vaccines and aims to demonstrate their effectiveness through preclinical models. Once the preclinical data is completed, the technology, materials, and expertise will be shared with other production partners. This approach is expected to expedite the development of H5N1 vaccine candidates and strengthen efforts for pandemic preparedness, as stated by the WHO.
Dr. Tedros Adhanom Ghebreyesus, WHO Director-General, emphasized that the initiative reflects the goals of the mRNA Technology Transfer Programme to promote increased research, development, and production in low- and middle-income countries. This, in turn, aims to ensure a more effective and equitable response to future pandemics.
This collaboration is significant as it marks the first instance of a vaccine developer voluntarily sharing its findings with a network of partner manufacturers established by the WHO. The WHO clarified that although Sinergium's mRNA flu vaccine has not yet undergone human testing, it will need to undergo clinical trials before it can be utilized.
by RTTNews Staff Writer
For comments and feedback: editorial@rttnews.com
BYLINE: Lauren Quinn
URBANA, Ill. -- A bad case of the flu during pregnancy can increase the risk for fetal neurodevelopmental disorders such as schizophrenia and autism spectrum disorder. But its not the virus itself doing the damage; its the mothers immune response.
NewUniversity of Illinois Urbana-Champaignresearchusing live mouse-adapted influenza virus improves upon previous mouse experiments to explain the process on a cellular and molecular level. It also indicates fetal brain changes are more likely once the severity of the mothers infection meets a specific threshold.
Our data provide really compelling evidence for an infection severity threshold, which mimics what we see in humans. There are only a subset of maternal infections that are going to be severe enough to cause concerns like this. That said, pregnant people should definitely get the flu vaccine to reduce their risk, said senior study authorAdrienne Antonson, assistant professor in theDepartment of Animal Sciences, part of theCollege of Agricultural, Consumer and Environmental Sciencesat Illinois.
The study is one of only a handful to investigate maternal infection in mice using live influenza virus at doses that replicate seasonal flu outbreaks in humans. That means our results are more relevant to human pathological infection, said lead study authorAshley Otero, a doctoral student in theNeuroscience Programat Illinois.
Antonsons team infected pregnant mice with live influenza A virus, rather than a viral mimic an inert molecule that mimics viral behavior used by most research groups in recent decades. The viral mimic elicits the innate immune response, broadly categorized as non-specific inflammation, that occurs within 24 to 48 hours of infection.
These studies have provided important clues about which inflammatory proteins are made by the mother and how they interact with the fetal brain. But Otero says viral mimics may prompt slightly different immune responses than the live virus in both mother and fetus, and they fail to capture what happens during the mothers adaptive immune response, which occurs later and helps an animal remember past infections.
To address these issues, the team subjected the mice to one of two doses of the virus representing a moderate or severe infection at the moment in gestation closest to the end of the first trimester in humans. Then, at two and seven days post-infection, they tracked how the infection progressed in the lungs and intestines of the mother, as well as how products from the mothers immune response interacted with the fetal brain. They also measured the physical properties of fetal brains, including the thickness of the cortex, which has been linked to neurodevelopmental disorders in humans.
Several important viral mimic studies in mice have implicated an immune protein called interleukin-17 primarily manufactured by T helper (Th)-17 cells in the mothers intestinal tract in changes to the fetal brain and neurodevelopmental disorder-like behaviors after birth. But the live virus didnt activate that protein.
At first, when I saw that interleukin-17 was not elevated in our moms from influenza infection, I was convinced we wouldnt see any changes in the developing fetal brain, Otero said. But interestingly, we did see very similar responses in the developing neocortex, including dramatic reductions in the upper neuronal layers in fetuses from moms who had the higher-dose infection.
Otero further explains that postmortem human studies have documented smaller cortical structures in people with schizophrenia and autism spectrum disorder. So, our results were really in line with what we see in human brains.
Antonson added, We dont think it's ever going to be just one inflammatory molecule that's causing all these different things. But this is the first time this pathway has been thoroughly investigated and compared against models that, thus far, have demonstrated that interleukin-17 is really involved. Thats why its important to move beyond viral mimic models to the true live virus.
Having ruled out interleukin-17, at least at the time points they studied, the team tracked immune cells in the fetal brain. Microglia, which infiltrate the brain and interact with developing neurons, had signatures of increased inflammatory activity in fetuses from high-dose flu-infected mothers. Fetal border-associated macrophages (BAMs), which border the brains surfaces and provide constant immune surveillance, were also more active and abundant. Both cell types normally aid in healthy brain development, but Otero and Antonson think that when theyre spurred into an overactive state, they could attack instead of support healthy developing neurons.
Viral mimic studies have also implicated overactive microglia in causing fetal brain deformities, but BAM activity is vastly understudied. Otero plans to follow up with more research to understand the role of BAMs in prenatal influenza infection.
Antonson emphasizes that maternal infection is only one of many risk factors for neurodevelopmental disorders.
These disorders are caused by a multitude of elements, including environmental factors, genetics, pharmacological exposures, and more. We're focusing on just this in-utero period, but the early postnatal period is important, and adolescence is important. Its just one slice of a very complicated pie.
The study, Influenza A virus during pregnancy disrupts maternal intestinal immunity and fetal cortical development in a dose- and time-dependent manner, is published inMolecular Psychiatry[DOI:10.1038/s41380-024-02648-9]. The research was supported by the Roy J. Carver Charitable Trust (grant #23-5683), USDA NIFA Research Capacity Fund (Hatch project #ILLU-538-940), the Department of Animal Sciences, and the College of ACES.
Antonson is also affiliated with theBeckman Institute, theMicrobial Systems Initiative, and theCarl R. WoeseInstitute for Genomic Biologyat Illinois.
Bird flu snapshot: This is the latest installment in a series of regular updates on the H5N1 flu outbreak in dairy cows that STAT is publishing on Monday mornings. To read future updates, you can also subscribe to STATs Morning Rounds newsletter.
A network of nascent vaccine manufacturers in low- and middle-income countries will soon start preliminary work to develop messenger RNA vaccines targeting the H5N1 bird flu virus, an effort that could speed production during a pandemic, should this virus trigger one.
The World Health Organization announced Monday that Argentinas Sinergium Biotech will begin doing pre-clinical testing of candidate vaccine viruses for H5N1 using mRNA technology. The company, which is doing the work at the behest of the Argentinian government, is part of a network of emerging manufacturers that have been working with the WHO and the Medicines Patent Pool to expand mRNA production capacity around the globe.
The announcement comes following a week in which the human count of H5N1 cases associated with the ongoing outbreak in cows in the United States hit 13 and the cumulative number of herds that have tested positive for the virus climbed to 172 in 13 states. That number is widely believed to be an underestimate of the true scale of the outbreak in dairy cattle.
All of the human cases appear to stem from infected livestock, not person-to-person spread. Ten of the human cases have been detected in Colorado, which currently tops the list of states with infected herds. The other three were diagnosed previously in Michigan (two) and Texas (one).
Four of the human cases are in farmworkers who contracted the virus while working in dairies. The remaining nine are in workers who were culling large poultry operations in Colorado. Genetic analysis of the viruses in the infected poultry operations showed that it belongs to the same strain that is spreading in cows. High temperatures in the poultry barns reportedly rendered personal protective equipment ineffective. All human cases in this outbreak have involved mild illness.
The Centers for Disease Control and Prevention said although the number of human cases have climbed, its assessment of the risk the current situation poses has not changed. The CDC suggests that at present the risk to the general public is low.
There are no signs of unexpected increases in flu activity otherwise in Colorado, or in other states affected by H5 bird flu outbreaks in cows and poultry, it said in a statement released late last week. To date, we have not seen genetic changes in the virus that would make it more likely to transmit between humans, but we are closely monitoring it.
The world is watching the outbreak in the U.S. and there have been reports of discussions among countries and vaccine manufacturers about production of pandemic flu vaccine, should it be needed.
The goal of the mRNA vaccine manufacturing network and this work led by Argentina is an effort to try to prevent low- and middle-income countries from finding themselves without access to vaccines when the next pandemic occurs, WHO officials said.
Affluent countries bought their way to the front of vaccine delivery queues during the 2009 H1N1 influenza pandemic and again in 2020-2021, when vaccines for Covid-19, the first to use mRNA technology, became available.
We saw during Covid that those regions that dont have vaccine manufacturing, they are the last in line to receive it, Martin Friede, team lead for the WHOs vaccines research unit, told reporters on Friday.
Sinergium will share its findings with others manufacturers in the 15-member network, Friede said. So the other partners dont need to make the significant intellectual and financial investments in developing their own H5N1 candidates. Countries in the network include Vietnam, Bangladesh, Nigeria, Ukraine, and Egypt.
After the 2009 pandemic, the WHO, with funding from the U.S. and other governments, worked with developing countries to create capacity to produce flu vaccines in markets with no domestic capacity. But most of those facilities were eventually shuttered, Friede said, because those markets dont use significant amounts of seasonal flu vaccine.
The hope this time is that mRNA is a more nimble technology which can be used to produce vaccines and therapeutics that developing countries actually need regularly, which will keep facilities running so theyre ready to turn to pandemic vaccines then they are needed, he said.
As one example, South Asian members of the network may produce vaccines to protect against enterovirus 71, which causes hand, foot, and mouth disease, a common ailment in that part of the world, he said. The facility in South Africa is pursuing production of tuberculosis vaccines.
Weve done this before. This time were doing it right, Friede said.
If a pandemic caused by H5N1 or another virus were to begin in the near term, this work would not prevent another global shortage of vaccine, he stressed.
But if it was to start next year, already the work thats been done this year would mean that all of the partners would be in a better position. He noted that some members of the network have not yet begun to build mRNA manufacturing infrastructure.
But we have about half that have got some [good manufacturing processes] manufacturing capacity and have begun installing necessary equipment so that if a pandemic was to happen, they would be better able to roll out, Friede said.
Chickens stand in their cages at a farm in 2009, near Stuart, Iowa. Millions of chickens have been culled in Iowa, Colorado and other states since 2022 in response to the current H5N1 bird flu outbreak. Charlie Neibergall/AP hide caption
For nearly four months, the spread of bird flu in the nations dairy cattle has stoked fears that, if left unchecked, the virus could eventually unleash a pandemic.
The recent cluster of human cases connected to poultry farms in Colorado only underscores that the threat remains real.
Genetic sequencing of the virus collected from the sickened poultry workers closely resembles whats circulating in dairy herds, suggesting that cattle somehow introduced the virus into the poultry flock.
At one massive poultry facility, workers culled the birds under particularly dangerous circumstances.
As health officials describe it, they struggled to properly wear protective equipment over their mouth, nose and eyes as they handled thousands of sick birds in a sweltering barn, with industrial fans blowing feathers and other potentially virus-laden material into the air.
Given these conditions, its far from surprising that people would catch the virus themselves, says Jennifer Nuzzo, an epidemiologist at Brown University.
Its gambling with peoples lives, she says. Theres no other way to describe it.
State and federal health officials are still investigating the scope of the outbreak, although so far all of those whove tested positive have only had mild, flu-like symptoms.
Nuzzo says the spillover at the poultry farms drives home the risks of having a viral reservoir in dairy herds that offers the virus ample opportunities to jump between species and potentially adapt to mammals.
Every time you give an avian virus a chance to infect a human, its like buying a ticket for a lottery you don't want to win, says Troy Sutton, a virologist at Penn State University who studies transmission of bird flu.
Based on the newest research, heres what scientists are learning and concerned about as they study the virus.
Luckily, theres no indication that we have drawn the dreaded winning ticket. At least not yet.
The virus working its way through dairy cattle is still fundamentally well-suited to infect birds, not people; however, there are clearly some mutations helping it maintain a foothold in mammals, says Thomas Peacock, a virologist at the Pirbright Institute in the U.K. who studies avian influenza.
I wouldn't be surprised if it's quite a lot more infectious at the same doses, than a purely avian virus that would have been seen last year in poultry, says Peacock, adding that this may give it a leg up when it comes to infecting humans, too.
Scientists are still trying to get a better sense of what exactly these changes in the dairy cattle version of H5N1 are doing, but he says there are certainly some mutations that are already enhancing its ability to replicate in mammalian cells.
Of most concern would be the virus evolving to get better at using the type of receptors found in the upper respiratory tract of humans. Such a change could let bird flu spread easily via the airborne route between people similar to the seasonal influenza viruses that typically infect humans.
Peacock and other scientists are closely watching for changes in hemagglutinin proteins on the surface of the virus which would be ground zero for this development.
There are still many outstanding questions about how exactly humans are catching the virus.
One possibility, raised by federal health officials, is that a splash of milk, say, in the eyes or elsewhere could explain some of the infections in dairy workers, particularly those whose only symptoms were conjunctivitis. Theres also speculation that aerosolized milk could be another source of infection.
While the virus still doesnt do well in the upper respiratory tract of humans, Peacock says, evidently there's a degree of replication because nasal swabs are testing positive for low amounts of viral genetic material, at least in some of the human infections.
Research on avian influenza predating the dairy cattle outbreak has shown that, with only a few mutations artificially inserted, airborne transmission can take place between ferrets, which are used as a model of human infection.
Since the dairy cattle outbreak began, scientists have begun to analyze how this version of the virus spreads, in hopes of understanding the threat it poses to humans.
The latest research, which comes from a team at the University of Wisconsin-Madison, shows the virus can be transmitted by respiratory droplets in ferrets, but inefficiently.
Amie Eisfeld, an author of the study, says their lab has not seen this kind of transmission event with any other version of highly pathogenic avian influenza that theyve isolated from the natural world and tested in ferrets.
There are features present in this virus that are concerning, says Eisfeld, a researcher at the University of Wisconsin-Madison. Its important to be monitoring what is happening here, and to limit infections in cows and exposure in humans.
In the experiment, only one of the four exposed ferrets caught bird flu from respiratory droplets. That animal didn't have any virus in the nasal swabs, but there were antibodies in the blood showing it had been exposed.
Sutton notes that just because a ferret in the lab caught the virus in this way doesn't necessarily mean humans will.
In another troubling finding from the study, the team discovered that the virus can bind to the type of receptors found in the upper respiratory tract of humans, suggesting it does possess features that may facilitate infection and transmission in mammals, the authors write.
To figure this out, Eisfeld says they artificially generated these receptors and attached them to a piece of plastic and then added the virus to see if it would stick.
Because this wasnt done in actual people, she says the results need to be interpreted with caution: I wouldnt want to sound the alarm bells and [suggest] this is transmissible between humans.
Peacock, who was not involved in the work, says the results do suggest this virus is more infectious in mammals than previous avian viruses. And while it doesnt appear to be spreading between humans yet, he worries that could change. Its an influenza virus, if there's pressure for it to do something, it will learn to do it.
While this kind of finding is unnerving, Troy Sutton says it needs to be put in context -- lab experiments are essentially creating a pro-infection environment that may not reflect what happens outside of the lab.
This isn't exactly what a human nose is like out in the real world, he says. Theres snot and bacteria and there's all these other things that get in the way.
Its well-established that infected cattle are shedding high levels of virus in the milk for days or even weeks, before eventually recovering.
This has supported the hypothesis that the virus is primarily spreading from cow-to-cow during the milking process and through other shared equipment in the dairy barns rather than via the respiratory route.
However, some research hints that respiratory transmission cant be ruled out.
In one recent study, a small number of non-lactating cows were purposefully infected with aerosols containing bird flu, which was collected from cow milk. Only one of the four animals consistently had viral genetic material in nasal swabs, whereas the rest only had positive results some days. Autopsies showed evidence of viral replication in their lungs, although none of the cattle had serious symptoms.
In contrast, the lactating cattle that were deliberately infected on their teats quickly showed signs of disease and increasing viral loads.
Taken together, those findings bolster the hypothesis that contact with infected milk is a key source of infection, but they also suggest the respiratory route may still have a role to play, says Dr. Amy Baker, the lead author of the pre-print study and a research veterinary medical officer at the National Animal Disease Center in Ames, Iowa.
This doesn't really tell us whether or not this is a main way that it's transmitting in these dairy farms, but it points to the fact that we need to at least keep an open mind that respiratory infection and transmission could occur, she says.
To be clear: Theres no evidence yet that humans whove caught the virus have spread it to others, which is why the CDC still deems the risk to the general public low. Whats more, a recent study of Michigan dairy workers at two farms with outbreaks analyzed blood samples and found no antibodies suggesting past infections that went undetected.
The human infections that have cropped up all seem to have occurred in heavily virus contaminated, high virus dose environments, which is reassuring because it means that steps can be taken to minimize the spread, says Sutton.
If you started to see people getting infected, with low-virus doses, that would be alarming, he says.
Federal health officials maintain its still possible to quash the outbreak in dairy cattle.
Nuzzo is skeptical. Shes yet to see a clearly articulated, viable strategy for ending the spread. New cases are still popping up in dairy herds every week.
As a scientist tracking the situation from outside the U.S., Peacock struggles to make sense of how the government hasnt curtailed the spread of a virus that has true pandemic potential, even after months of mobilizing a response.
My feeling is that if there were even just moderate efforts to stop this, it would have been stopped already, he says.
Concerned about a recent jump in human infections with influenza viruses of avian origin in the region, the United Nations Food and Agriculture Organization(FAO) is calling for urgent action in the Asia-Pacific area in order to create a holistic approach to disease management.
Stressing the need for a united response, it wants to see surveillance systems implemented, capacity building in diagnostics, and full and timely data sharing between sectors. In particular, the agency is looking for full genome sequencing in order to monitor the spread of the virus, and its evolution.
Governments, international organizations, and the private sector must collaborate and share information transparently and in a timely manner to devise effective containment strategies, FAO said.
Specifically for the regional poultry sector, the agency described strengthening of biosecurity measures as imperative, along with effective vaccination strategy.
It also called for awareness to be created among health providers and the general public in its 13member nations in the Asia-Pacific regarding the human health risks from sick and dead poultry.
In recent years, few infections in people were reported in this region, according to the FAO.
However, over the past few months, 13 cases have been recorded in Cambodia, and others in China and Vietnam. This is a cause for concern for the FAO, along with the emergence of a new strain of avian influenza(A) virus.
Since late 2023, we have observed a rise in human cases and the virus spreading to new animal species, said Kachen Wongsathapornchai, who is Regional Manager of FAO Emergency Centre for Transboundary Animal Diseases (ECTAD). The emergence of novelA/H5N1 strains, which are more easily transmissible, increases the pandemic threat.
For the FAO, the threat is exacerbated by the ever wider geographical spread of the H5N1 highly pathogenic avian influenza (HPAI) virus serotype, and its ability to infect new species of wild and domestic animals. Furthermore, there are particular additional risks in some regions, including generally low levels of biosecurity in the Greater Mekong sub-region, Indonesia, and the Philippines. While some other nations may be insufficiently prepared for the return of avian influenza, others including Bangladesh, India, and Nepal are already battling to control outbreaks, says the FAO.
Kachen called for the region to take immediate coordinated preventative measures.
Supporting this call for action is the latest news from the World Health Organization.
Its latest report on the avian influenza(A) situation in the Western Pacific Region includes a further human case in China reported in the period July19-25. A 70-year-old woman in Anhui province who became unwell in mid-June tested positive for the H5N6 virus variant. She died in early July.
This patient was the 93rdconfirmed infection with this particular virus type in the region since 2014, and the 57thto die.
Latest report from the dedicated Australian government websiteconfirms a total of 16 HPAI outbreaks in poultry linked to viruses of the H7 family. The first cases were confirmed in mid-May, and no new cases have been confirmed over the past week.
Of these outbreaks, eight occurred at premises in the state of Victoria, six in New South Wales, and two in the Australian Capital Territory(ACT). All premises have been depopulated.
According to earlier notifications to the World Organisation for Animal Health(WOAH), four of the flocks were described as backyard or hobby flocks, and tested positive for the H7N8virus variant as have those at four commercial farms. At another seven farms, presence of the H7N3virus was confirmed, while the H7N9serotype was found at just one farm.
Total number of poultry impacted by the ongoing disease waves in Australia has just passed 1.8million.
In the Philippines, there has also been no change in the HPAI situation, according to the latest update from the Department of Agriculture(DA) Bureau of Animal Industry. As of July19, there are just three ongoing outbreaks in the country. All involve the H5N1 virus serotype, and are affecting three poultry farms in the province of Pampanga in the Central Luzon region.
View our continuing coverage of the global avian influenza situation in poultry, and on disease developments in the U.S.
With the number of U.S. dairy herds infected with H5N1 bird flu rising almost daily, fears are growing that the dangerous virus cannot be driven out of this species. That belief is amplifying calls for the development of flu shots for cows.
Multiple animal vaccine manufacturers are reportedly at work trying to develop such products. And the U.S. Department of Agriculture is eagerly encouraging the effort, detailing in a notice last week what kinds of evidence would be needed to win licensing approval for cow vaccines.
But a number of scientists question whether investing too heavily in this strategy is a wise approach at this point, given that there remain many outstanding questions about whether vaccinating cows would be an effective way of stopping spread of the virus in cattle in the first place. Some wonder whether farmers will be willing to absorb the costs of vaccines to prevent an infection they dont currently view as a serious threat to their operations, or whether they would agree to the stringent post-vaccination surveillance that must go hand-in-glove with any attempt to use vaccines to solve this vexing problem.
To date dairy farmers have, in large measure, refused to cooperate with efforts to chart how deeply the virus has infiltrated U.S. herds, seeing the possible stigma of admitting they have H5N1-infected cows as a greater risk than the virus itself.
Despite the USDAs program to compensate farmers for production losses and their and other agencies efforts to incentivize more testing of cows and people at-risk, distribute [personal protective equipment], etc., there doesnt seem to be widespread enthusiasm, said Angela Rasmussen, a virologist at the University of Saskatchewans Vaccine and Infectious Disease Organization in Saskatoon, Canada. That makes me wonder how willing producers would be to vaccinate their entire herds even if a vaccine were available, especially if it costs them any money at all. For large herds, this could mean a substantial investment.
Rasmussen is one of a number of experts STAT spoke to who are not convinced cow flu shots are the answer to this dilemma. The need to stop transmission of the virus in cows is pressing more, really, for us than for the animals themselves. The longer it transmits among mammals, the better adapted to mammalian species it will become. The changes it will acquire in that process could make it better equipped to transmit to and among people.
Many scientists watching the U.S. situation unfold believe traditional containment measures, strictly applied, could drive the virus from cows. More limits on movement of cows. Aggressive testing of herds, possibly through the sampling of bulk tanks on farms. More stringent biosecurity.
To be clear, the USDA also contends the spread of H5N1 in dairy cattle can be stopped through traditional containment measures. Enhanced biosecurity [within the industry] should get us to a point where we can arrest the spread, Eric Deeble, USDAs acting senior adviser for the H5N1 response, reiterated earlier this month at a press conference. In a previous news conference, Deeble said vaccines for cows would take some time to develop, and containment should be achievable before they are ready.
We hope that through enhanced biosecurity and additional testing that we will be able to eliminate this disease from the dairy herd in the absence of a vaccine, although we believe that they may be helpful down the line, he said, adding the USDA hopes its programs to help pay for measures aimed at reducing the spread of H5N1, and to compensate for lost milk production, will entice dairy farmers to take the steps needed to lower the risk of transmission. The departments production loss compensation program requires positive test results to make a claim, which could make more visible the actual scope of the problem, if farmers apply for it.
In the nearly one month since the program was launched, 12 applications have been submitted, Marissa Perry, USDAs deputy director of communications, told STAT in an email.
Thats out of 172 herds with confirmed bird flu infections, and the untold others where the virus has infected cows but farmers some of whom view bird flu as just one more health problem cows occasionally develop havent bothered to test. Some may have done what a canny Oklahoma farmer did in mid-April when faced with the possibility of H5N1-infected cows: Collected swabs and stored them, only submitting them for testing after the USDAs milk compensation program went into effect. (They were positive.) Under a federal regulation that came into effect at the end of April, all positive H5 tests must be reported to the USDA.
Florian Krammer, an influenza virologist at Mount Sinais Icahn School of Medicine in New York who has worked on developing human vaccines, is hopeful about the prospect of administering flu shots to cows. In fact, earlier in this outbreak Krammer raised the possibility of giving stockpiled H5N1 vaccines made for people to cows to try to quell spread of the virus.
Experts who are more skeptical of the utility of vaccinating cows counter that human flu vaccines produce underwhelming results when used in people, and may not do what we need them to do in cattle. In people, they do reduce the risk of serious infection requiring hospitalization and of death, but have much more modest impact if any on preventing infection or blunting onward transmission, said Michael Osterholm, director of the University of Minnesotas Center for Infectious Disease Research and Policy. CIDRAP has studied the real-world effectiveness of flu vaccines in depth.
Krammer doesnt necessarily see that as a problem when it comes to cows. In people, flu vaccines, which are injected into the arm, dont trigger production of antibodies that can neutralize virus in the upper respiratory tract, where infection occurs. Cows udders, where H5N1 infection is believed to take hold in most cases, produce high levels of this kind of antibody, known as IgG.
Were talking about an anatomic site that has tons of IgG. Thats exactly the antibodies that you would get with intramuscular vaccination, he said. Its not clear if this is going to be 100% effective in stopping transmission. Its unlikely. But if you combine that with other measures, it could be used as a tool to cut down on transmission.
Thijs Kuiken, a Dutch pathologist who has studied H5N1 for two decades, thinks the U.S. needs to mount a broad response to solve its H5-in-cows problem. But, like Krammer, he also believes cow vaccines could help. It would most likely reduce infection, reduce secretion [of virus], therefore slow down transmission, and therefore help to stop an epidemic, said Kuiken, a professor in the department of viroscience at Erasmus Medical Center in Rotterdam.
Other experts question whether enough is known about what we actually need cow flu vaccines to do to start designing these products. Osterholm has led efforts to develop what are known as target product profiles for other vaccines, including one for a universal flu vaccine for people. A TPP is effectively the list of criteria a vaccine should meet to be effective. Knowing how a virus spreads within the population you are trying to protect be it human or bovine is a prerequisite to figuring out how to design these vaccines, Osterholm noted.
Rasmussen agrees there are important gaps in our understanding of how H5N1 is moving from cow to cow and herd to herd. In her view, its unclear whether vaccines would solve or potentially exacerbate the spread of H5 in cows.
Would an intramuscular or intranasal vaccine work to prevent infection via the mammary gland? Would intra-mammary vaccination protect against infection by the respiratory route? How well would any of these vaccination approaches work to prevent disease and what impact would this have on milk production? she asked.
Since the very beginning of the outbreak, the USDA has said that it believes that, in the main, individual cows are becoming infected when they come in contact with contaminated milk that pools in milking machines as cows are led in and out in succession. It also believes the virus is spreading from herd to herd through other human-mediated means the movement of cows from infected herds within and across state lines, the trucks and other equipment that transport animals and supplies from farm to farm, and on the clothing of workers who pull shifts on more than one farm.
But once the virus is in a herd, does respiratory transmission occur? That, after all, is the way humans infect one another with flu. Results of efforts to get to the bottom of this question have been mixed to date. A preprint a scientific paper that hasnt yet been through peer review posted online by scientists from USDAs National Veterinary Services Laboratories in Ames, Iowa, reported on the experimental infection of heifers and lactating cows. They found respiratory transmission can occur, though hypothesized that infection in the mammary gland likely lasts longer. And a study published this week in Nature that is based on an analysis of spread of the virus through nine farms across four states also pointed to respiratory transmission playing some role in transmission of the virus.
But Jrgen Richt, a veterinarian and director of the Center of Excellence for Emerging and Zoonotic Animal Diseases at Kansas State Universitys College of Veterinary Medicine, conducted experimental infections of cows and did not see evidence of spread of the virus via the respiratory tract.
My conclusion from my studies is the respiratory route is not the major route of transmission, Richt told STAT. But will there be instances where it could happen? Most likely. If you have thousands of animals. Some are sick. They have bacterial infections on top [of flu]. Crowding. These are conditions we cannot replicate. Our [lab] animals are housed in, like, a five-star hotel.
Does it matter? In a word, yes. If a vaccine protects udders but does not protect respiratory tracts, the most obvious signs that this virus is spreading in a herd reduced milk production and thickened, discolored milk could disappear, making a currently hard-to-detect problem virtually invisible. There is already evidence that respiratory infection in cows is more subtle than infection in the udder. The preprint on the experimental infection work conducted by the USDAs scientists notes that signs of clinical disease may not be recognized under field conditions, particularly from a respiratory route of exposure.
If cow vaccines could induce whats called sterilizing immunity immunity that prevents infection, not just lessening the illness that infection causes flu virologist Thomas Peacock said hed be more enthusiastic about the idea. But flu vaccines as we know them dont do that, said Peacock, an expert at Britains Pirbright Institute, which focuses on controlling viral illnesses in animals.
Peacock suggested hes left with the sense that cow vaccines are a fallback solution, an easier out than putting in place policies that the industry doesnt want to have to adopt.
At the moment it just feels like, well, we have to do something, but we dont want to do the expensive, disruptive thing, and therefore were going to do the cheap, good-sounding thing, Peacock said. It really feels like a last resort that we shouldnt have to be going to.
He and Kuiken likened going the vaccine route to admitting defeat an acknowledgement that the dairy industry cannot be cajoled, enticed, or even coerced into taking the steps needed to stop spread within U.S. herds.
My feeling is that if vaccination started to be used for cattle, that would be a huge admission of failure, Peacock said.
If cow vaccines are used, they will have to be deployed as part of a series of measures, the most important of which would be surveillance, said Marion Koopmans, who heads the viroscience department at Erasmus Medical Center. The aim would be to detect transmission that the use of vaccines might mask. The full blocking or elimination of virus is unlikely. So you will need to make sure you have ways of picking up circulation that might have become silent, because vaccination is more likely to suppress the symptoms, she said.
David Swayne, an avian influenza expert who worked for the USDA for nearly 30 years and is now a private consultant, agreed that vaccination of cows would have to be done as part of a more multifaceted response. Its not just about injecting a vaccine, he said. You need to then follow up to look serologically, and then you also need to follow up to make sure theres no virus by testing, lets say, bulk milk or something like that. Surveillance is really a critical part of any kind of vaccination program for a severe disease like [highly pathogenic avian influenza.]
Swayne acknowledged the concerns about the unanswered questions about how H5N1 is spreading in cows, but he said vaccine manufacturers should be working on vaccines while researchers are seeking those answers. Vaccines may be a necessary tool for controlling this disease in the future. Instead of waiting until you answer all the questions on pathogenesis, its good to go ahead and start working on those vaccines now, so that when you get to the end, and you have all your answers, youve got the vaccines ready for that final step, he said.
As the bird flu outbreak in dairy cows has ballooned, officials have provided repeated reassurances: The virus typically causes mild illness in cows, they have said, and because it spreads primarily through milk, it can be curbed by taking extra precautions when moving cows and equipment.
A new study, published in Nature on Tuesday, presents a more complex picture.
Some farms have reported a significant spike in cow deaths, according to the paper, which investigated outbreaks on nine farms in four states. The virus, known as H5N1, was also present in more than 20 percent of nasal swabs collected from cows. And it spread widely to other species, infecting cats, raccoons and wild birds, which may have transported the virus to new locations.
Theres probably multiple pathways of spread and dissemination of this virus, said Diego Diel, a virologist at Cornell University and an author of the study. I think it will be really difficult to control it at this point.
The outbreak, which officials first announced in March, has spread to at least 170 dairy farms in 13 states, according to the Department of Agriculture. It has also jumped into poultry farms and infected at least 10 farmworkers exposed to infected cows or poultry.
The exact origins of the outbreak remain unknown, but scientists believe that the version of H5N1 that is now circulating in dairy herds probably jumped into cows just once, most likely in late 2023 in the Texas Panhandle.
In the new study, the scientists focused on nine farms five in Texas, two in New Mexico and one each in Kansas and Ohio that reported outbreaks between Feb. 11 and March 19. When they analyzed samples of the virus taken from affected farms, they found that those samples were closely related to one collected from an infected wild skunk in New Mexico in February.
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Health Analysis
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Posted: July 25, 2024 Last Updated: July 25, 2024
The sheer scale of the U.S. bird flu outbreak is hard to fathom.
More than 100 million farmed birds have been infected with H5N1 since 2022, followed by roughly 170 herds of dairy cows, along with virus detections in more than 200 other mammals humans included.
Colorado is now facing the country's first human outbreak, which hasquickly hit the double-digits. As of Wednesday, there have been nine recent cases at two poultry farms, plus one earlier case from a dairy farm. And while the latest spread may bechicken-to-human, genetic sequencing suggests the virus strain is similar to the form of bird flu tearing through cow populations across more than a dozen states.
The country's total human infection tally pales in comparison to the staggering case counts among poultry and livestock. There haven't been any farm worker deaths, and no cases linked to dairy farms have popped up yet in Canada, either.
Yet this new, unusual cluster of human H5N1 cases may be a harbinger of looming challenges to come, all while the broader U.S. outbreak could be surging out of control.
The timing is far from ideal, several scientists told CBC News, with farm worker infections ticking up mere months before the return of the usualflu season, and the fall migration of millions of wild birds giving this globetrotting virus countless more opportunities to evolve.
"We are looking at, potentially, a huge outbreak that is still expanding, and still growing, and that is not containable," warned virologist Angela Rasmussen, a researcher with the University of Saskatchewan's Vaccine and Infectious Disease Organization.
"And that increases the risk of more and more human cases, which in turn increases the risk that this virus will become better adapted to humans."
Officials first announced the discovery of several farm worker infections back on July 14, all linked to large-scale culling efforts involving H5N1-infected birds on an egg farm in Colorado.
While there aren't signs of onward human-to-human transmission, sequencing from one of those cases showed the strain is closely related to the virus spreading in dairy cows, which features previously-documented adaptations to mammals, the U.S. Centers for Disease Control and Prevention noted in a recent update.
More reassuring? So far, all thehuman cases in the U.S. have been mild infections, despite high H5N1 case fatality rates reported globally over the last two decades. Some farm workers in the Colorado cluster had traditional flu symptoms of fever and cough, while others experienced conjunctivitis, suggesting the virus may have snuck in through their exposed eye membranes rather than through the body's respiratory channels.
But given the small number of known human infections in the U.S. todate, and the unusual transmission patterns that don't mimic how this virus would actually spread person-to-person, "we should put no stock at all on what we're seeing in terms of severity," notedMcMaster University influenza researcher Matthew Miller, the director of the Michael G. DeGroote Institute for Infectious Disease Research.
If human infectionskeep rising into the fall, in Colorado or beyond, experts say the timing would be advantageous to a virus that's already proven quite adept at striking a wide variety of species. And a host of factors, several scientists agreed, may provide opportunities forH5N1 to better adapt to infect and harm more human hosts.
For one thing, the dovetailing of heightened human H5N1 circulation and the return of seasonal flu strains could have dire consequences, said virologist Tom Peacock, a fellow with the Pirbright Institute, a U.K.-based research and surveillance centre for zoonotic viruses.
"Suddenly, some of these workers who are getting exposed and infected [with H5N1] have a chance of being infected with seasonal flu. And then the poultry or dairy worker is acting as the mixing vessel."
Those scenarios would give the virus a chance to mash up its genetic makeup with other flu strains, potentially allowing it to mix-and-match characteristics that could sharpen its ability to transmit person-to-person. It's a process known as reassortment, and influenza virusesare particularly adept at it.
That genetic reassortment, Miller said, "could create a whole new beast."
There's also a heightened risk of other farms becoming infection sites in the months ahead, Peacock warned, given H5N1's penchant for spilling between species.
Already, mounting evidence suggests heightened mammal-to-mammal transmission is taking place even now. A peer-reviewed paper in Nature, published onlineWednesday, looked at genomic sequencing for a host of infected species, including cows, birds, domestic catsand a raccoon from impacted farms.
The research team found evidence of both "multidirectional interspecies transmissions" and "efficient cow-to-cow transmission" afterseemingly healthy cows from an affected farm were transported to a facility in a different state.
The possibility of onward spread into pig populations in the months ahead is one of Peacock's biggest concerns,since swine "have a lot of viruses circulating within them that are derived originally from human seasonal viruses."
"This is how pandemics happen: The mixing of seasonal viruses with avian viruses or novel viruses," he said.
The 2009 swine flu pandemic is one of the most familiar, resulting from a mashup of bird, pigand human forms of influenza A.
Miller agreed the possibility of that happening on U.S. pig farms is a rising threat. "We're not doing enough proactive surveillance in those settings right now," headded. "It's a little frustrating."
On top of that, scientists expect another wave of migrations could further fuel H5N1's global spread, with millions of wild birds set to fly along north-south avian superhighways in the months ahead.
"There are tremendous opportunities [for H5N1] to recombine in new and unexpected ways as these waves of migration take place," Miller said.
All those added variables could make the U.S. bird flu outbreak even tougher to contain, heightening the risk to humans and putting other countries including Canada on alert.
"Eventually, if this continues, we will have viruses emerging that are better adapted to humans. What that's going to look like in practice, and whether that causes a pandemic, we don't know," said Rasmussen.
Complicating matters? The full extent of H5N1's human spread in the U.S. still remains hazy.
A recent serology study in Michigan, which involved testing blood samples from 35 farm workers who'd spent time around infected dairy cows, didn't find evidence of prior infections suggesting there might not be symptomless human infections flying under the radar.
But it's just one small study, from just one health department.
Colorado, meanwhile, isramping up surveillance efforts to combat the rampant spread of the virus,including a mandatory order on Tuesday for weekly bulk milk-tank testing at dairy farms. Twodays later, the state announced the launch ofa publicly-available dashboard to track cases of avian flu in humans, which will be updated twice a week.
Yet data from other states remains thin thanks to patchworktesting effortsmired by bureaucratic roadblocks, which means the U.S. is likely missing both animal and human cases, experts have warned for months.
"It's really hard to tell if Colorado was genuinely in a worse state than a lot of other states, or it's just testing and finding stuff," said Peacock."This is one of the major issues with this outbreak: We don't really have any idea."
Meanwhile, Rasmussen says there's "not really clear decisive action being taken" to clamp down on animal or human infections.
Alongside the need for heightened testing and surveillance efforts, she said H5N1 vaccination strategies targeting at-risk farm workers are another tool the U.S. should considerbefore the situation spirals out of control.
So far, however, the CDC has notrecommended vaccinations for any livestock workers.
Canada, Rasmussen said, should also remain vigilant, despite no known farm worker infections or any signs of the virus appearing in the country's milk supply. (Only one human case of H5N1 has ever been reported in Canada. The individual died from bird flu back in 2014 following a trip to China, where they likely got infected.)
WATCH | 20 years of warnings about H5N1 avian flu:
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Other countries are taking a differentapproach.In late June, Finland became the first to pursue proactive bird flu vaccination for any adults "who are at increased risk of contracting avian influenza due to their work or other circumstances."
The U.S. should take note, Rasmussen said, as sweltering temperatures in Colorado limited workers' ability to wear protective equipment while they were killing infected poultry leaving them vulnerable to catching the virus.
With more hot months ahead, and untold numbers of virus-carrying farm animals across the country, that scenario could easily happen again.
"It's a mistake not to offer some limited vaccination," Rasmussen said."Especially given the current situation."
Lauren Pelley Senior Health & Medical Reporter
Lauren Pelley covers the global spread of infectious diseases, pandemic preparedness and the crucial intersection between health and climate change for CBC. She's a two-time RNAO Media Award winner for in-depth health reporting in 2020 and 2022 and a silver medalist for best editorial newsletter at the 2024 Digital Publishing Awards for CBC Health's Second Opinion. Contact her at: lauren.pelley@cbc.ca
