Tag: Immunology

COVID-19 reactivates several latent viruses – particularly in ME patients

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Newswise — COVID-19 reactivated viruses that had become latent in cells following previous infections, particularly in people with chronic fatigue syndrome, also known as ME/CFS. This is the conclusion of a study from Linköping University in Sweden. The results, published in Frontiers in Immunology, contribute to our knowledge of the causes of the disease and prospects of reaching a diagnosis.

Severe, long-term fatigue, post-exertional malaise, pain and sleep problems are characteristic signs of myalgic encephalomyelitis/chronic fatigue syndrome, “ME/CFS”. The causes of the condition are not known with certainty, although it has been established that the onset in most cases follows a viral or bacterial infection. The health of the person affected is not restored even after the original infection is resolved. Indeed – the condition is sometimes known by its alternative name: post-viral fatigue. Since the cause is not known, diagnostic tests have not been developed.

“This patient group has been neglected. Our study now shows that objective measurements are available that show physiological differences in the body’s reaction to viruses between ME patients and healthy controls,” says Anders Rosén, professor emeritus in the Department of Biomedical and Clinical Sciences (BKV) at Linköping University, and leader of the study.

One theory that has been examined in several research studies is that a new infection can activate viruses that lie latent in the body’s cells after a previous infection. It has long been known that several herpes viruses, for example, can remain in a latent state in the body. Latent viruses can be reactivated many years later and give rise to a new bout of disease.

It has, however, been difficult to determine whether such reactivated viruses are involved in ME/CFS – until now. The extensive spread of the SARS-CoV-2 coronavirus during the COVID-19 pandemic has given researchers a unique opportunity to study what happens in people with ME/CFS during a mild virus infection and compare this with what happens in healthy controls.

In collaboration with the Bragée Clinic in Stockholm, the research group initiated a study early in the pandemic. Ninety-five patients who had been diagnosed with ME/CFS and 110 healthy controls participated in the study. They provided blood and saliva samples on four occasions during one year. The researchers analysed samples for antibodies against SARS-CoV-2 and latent viruses, and found a special fingerprint of antibodies against common herpes viruses in saliva. One of these viruses was the Epstein-Barr virus (EBV), which has infected nearly everybody. Most people experience a mild infection during childhood. People who are infected with EBV in the teenage years can develop glandular fever, commonly called mononucleosis, and also known as “kissing disease”. The virus then remains in a latent condition in the body. The EBV virus may proliferate in situations in which the immune system is impaired, causing fatigue, an autoimmune responses, and increased risk of lymphoma, if allowed to continue.

Approximately half of the participants were infected with SARS-CoV-2 during the first wave of the pandemic and developed mild COVID-19 (58% of those with ME/CFS and 41% of the control group). In more than one third of cases, infection had been asymptomatic, so the person had not been aware of the infection. After the SARS-CoV-2 infection had passed, however, the researchers detected specific antibodies in the saliva that suggested that three latent viruses had been strongly reactivated, one of them being EBV. The reactivation was seen both in patients with ME/CFS and in the control group, but was significantly stronger in the ME/CFS group.

Anders Rosén describes what happens as a domino effect: infection with a new virus, SARS-CoV-2, can activate other, latent, viruses in the body. The researchers suggest that this can, in turn, give rise to a chain reaction with an elevated immune response. This can have negative consequences, one of which is that the immune system attacks certain tissues, such as nerve tissue, in the body. Previous studies have also shown that the mitochondria, which produce energy in the cells, are affected, which suppresses the energy metabolism of people with ME/CFS.

“Another important result from the study is that we see differences in antibodies against the reactivated viruses only in the saliva, not in the blood. This means that we should use saliva samples when investigating antibodies against latent viruses in the future,” says Anders Rosén.

He points out that there is a great deal of overlap between the symptoms of ME/CFS and those of long COVID, which is experienced by around one third of patients who contract COVID-19. Exhaustion after light exercise, brain fog and unrefreshing sleep are common symptoms, while impaired lung capacity and abnormal senses of smell and taste are more specific for long COVID. The researchers believe that the results from the study can contribute to developing immunological tests to diagnose ME/CFS, and possibly also long COVID.

“We now want to continue and carry out more detailed investigations into the immune response in ME/CFS, and in this way understand the differences between the antibody responses against latent viruses,” says Eirini Apostolou, principal research engineer, and lead author of the article.

The study was financially supported by the Swedish Research Council, the Swedish Cancer Society and Linköping University. Some of the authors have financial interests in the Bragée Clinic.

The article: Saliva antibody-fingerprint of reactivated latent viruses after mild/asymptomatic COVID-19 is unique in patients with myalgic encephalomyelitis/chronic fatigue syndrome, Eirini Apostolou, Muhammad Rizwan, Petros Moustardas, Per Sjögren, Bo Christer Bertilson, Björn Bragée, Olli Polo and Anders Rosén, (2022), Frontiers in Immunology, published 20 October 2022, https://doi.org/10.3389/fimmu.2022.949787

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Linkoping University

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November 16, 2022
DNA barcoding reveals cancer cells’ ability to evade the immune system

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Newswise — Some cancer cells can deploy parallel mechanisms to evade the immune system’s defences as well as resist immunotherapy treatment, according to a new study from the Garvan Institute of Medical Research.

By suppressing the action of killer T-cells and hindering the ability of the immune system to flag tumour cells for destruction, breast cancer cells are able to replicate and metastasise, the researchers found.

“We know that breast cancer typically doesn’t respond well to immunotherapy, and we wondered if there’s an intrinsic mechanism enabling breast cancer cells to escape the immune system,” says first author Ms Louise Baldwin, who is a PhD student in Associate Professor Alex Swarbrick’s lab at Garvan.

The researchers used a technique called DNA barcoding, which tags cells with a known sequence and tracks the progression of tumour cells through time.

“We showed that there are rare cancer cells capable of escaping the immune system and escaping treatment with immunotherapy,” Ms Baldwin says.

The mechanisms could be used as potential targets for therapies, to stop tumorous cells from adapting and spreading. Another future application could be in prognosis, where a high number of cells could indicate which patients might not respond to immunotherapy.

The new study is published in Nature Communications.

While immunotherapy is an effective treatment in many cancers, in some people their cancer cells evolve to outplay the immune system defences. This process is known as immunoediting, where interaction between tumour cells and immune cells results in many cancerous cells being destroyed by the immune system, but leaving some undetected, which continue to grow and spread.

The researchers used mouse breast cancer cells tagged with a known DNA ‘barcode’, a sequence that was passed on from one generation of cells to the next.

The barcoding allowed the team to see where more aggressive, resistant cells came from, as they could trace it back to the original cell to see if it had grown or shrunk.

“Lead author Dr Simon Junankar wanted to understand whether resistance was adaptive – whether cancer cells duck and weave – or are they pre-programmed to evade the immune system,” says Associate Professor Alex Swarbrick, a laboratory head and Co-Lead of the Dynamic Cellular Ecosystems in Cancer Program at Garvan.

The team found that even before treatment, the cancer cells had diversified. “Some cells had already acquired the ability to evade immunity, meaning they have an innate ability to escape the immune system,” he says.

The cells seem to do this with parallel approaches. One way is to suppress the action of killer T-cells, which would usually destroy harmful cells. The other is to reduce the expression of MHC1 on cells, which act as a flag for the immune system to recognise harmful cells.

“Most tumour cells vanish when the immune system gets switched on, but a small proportion keep growing and expanding,” says Associate Professor Swarbrick.

“Tumours keep evolving and diversifying, and action by the immune system or treatment like chemotherapy is like pruning a tree – cancer cells get wiped out but the remaining branches on the tree continue to grow.”

The researchers also looked at the genetics of the cells, but there were no genes found to be associated, suggesting epigenetics might be at play.

–ENDS–

This research was supported by research grants from the National Breast Cancer Foundation (NBCF). Louise Baldwin is supported by an Australian Government research training (RTP) stipend and Associate Professor Swarbrick is the recipient of a research fellowship from the NHMRC.

Associate Professor Swarbrick is a Conjoint Associate Professor at St Vincent’s Clinical School, Faculty of Medicine and Health, UNSW Sydney.

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Garvan Institute of Medical Research

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November 7, 2022
Trinity Team Unearths Potential Secret to Viral Resistance

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Newswise — Scientists from Trinity College Dublin have unearthed a secret that may explain why some people are able to resist viral infections, having screened the immune systems of women exposed to hepatitis C (HCV) through contaminated anti-D transfusions given over 40 years ago in Ireland.

The extraordinary work, just published in leading journal Cell Reports Medicine, has wide-ranging implications from improving our fundamental understanding of viral resistance to the potential design of therapies to treat infected people.

Between 1977-79 in Ireland, several thousand women were exposed to the hepatitis C virus through contaminated anti-D, which is a medication made using plasma from donated blood and given to Rhesus negative women who are pregnant with a Rhesus positive foetus. The medication prevents the development of antibodies that could be dangerous in subsequent pregnancies. Some of the anti-D used during the 1977-79 period was contaminated with hepatitis C.

From this outbreak, three groups of people were identifiable: those who were chronically infected; those who cleared the infection with an antibody response; and those who appeared protected against infection without making antibodies against hepatitis C.

Cliona O’Farrelly, Professor of Comparative Immunology in Trinity’s School of Biochemistry and Immunology, is the senior author of the research article. Cliona, who is based in the Trinity Biomedical Sciences Institute, said:

“We hypothesised that women who seemed to resist HCV infection must have an enhanced innate immune response, which is the ancient part of the immune system that acts as a first line of defence.

“To test this we needed to make contact with women exposed to the virus over forty years ago and ask them to help us by allowing us to study their immune systems to hunt for scientific clues that would explain their differing responses.

“After a nationwide campaign over 100 women came forward and we have gained some unique and important insights. That so many women – many of whom have lived with medical complications for a long time – were willing to help is testament to how much people want to engage with science and help pursue research with the potential to make genuine, positive impacts on society. We are deeply grateful to them.”

The scientists ultimately recruited almost 40 women from the resistant group, alongside 90 women who were previously infected.

In collaboration with the Institut Pasteur in Paris they then invited almost 20 women in each group to donate a blood sample that they stimulated with molecules that mimic viral infection and lead to activation of the innate immune system.

Jamie Sugrue, PhD Candidate in Trinity’s School of Biochemistry and Immunology, is first author of the research article. He said:

“By comparing the response of the resistant women to those who became infected, we found that resistant donors had an enhanced type I interferon response after stimulation. Type I interferons are a key family of antiviral immune mediators that play an important role in defence against viruses including hepatitis C and SARS-CoV-2, or COVID-19.

“We think that the increased type I interferon production by our resistant donors, seen now almost 40 years after the original exposure to hepatitis C, is what protected them against infection.

“These findings are important as resistance to infection is very much an overlooked outcome following viral outbreak, primarily because identifying resistant individuals is very difficult – since they do not become sick after viral exposure, they wouldn’t necessarily know that they were exposed. That’s why cohorts like this, though tragic in nature, are so valuable – they provide a unique opportunity to study the response to viral infections in an otherwise healthy population.”

The lab’s efforts are now focused on leveraging these biological findings to unpick the genetics of viral resistance in the HCV donors. Their work on HCV resistance has already helped ignite international interest in resistance to other viral infections, including SARS-CoV-2, the virus that causes COVID-19.

The O’Farrelly lab has expanded its search for virus-resistant individuals by joining in the COVID human genetic effort (www.covidhge.com) and by recruiting members of the public who have been heavily exposed to SARS-CoV-2 but never developed an infection (www.viralresistanceproject.com).

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Trinity College Dublin

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November 4, 2022
Research team discovers central functions of innate immune cells

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Newswise — Inflammation and increased mucus production are typical symptoms of worm infections and allergies. This immune response involves our innate immune cells, but their exact functions are not yet fully understood. A research team from Charité – Universitätsmedizin Berlin has now shed light on the key tasks that these cells perform. In the study, which has been published in the journal Nature*, the researchers also identify potential therapeutic approaches for the treatment of allergies.

The human immune system is made up of two interconnected branches: the adaptive immune system, which learns something new with every infection and constantly develops over the course of a lifetime, and the innate immune system, which is less specialized but reacts particularly quickly and effectively. The cells of the innate immune system are located in the mucous membranes of the respiratory tract and the intestine, where they form a first line of defense at the point of entry for pathogens. These cells include group 2 innate lymphoid cells (ILC2s for short), which are active in the intestine in the case of parasitic diseases, and in the respiratory tract in the case of allergies.

“Innate lymphoid cells were discovered a decade or so ago and we already know a lot about them, but their exact function in the machinery of the immune system is not yet completely understood,” explains Dr. Christoph Klose, who heads the Emmy Noether Independent Junior Research Group on the regulation of type 2 immune responses by neuropeptides and neurotransmitters at the Institute of Microbiology, Infectious Diseases and Immunology at Charité. “There is a group of adaptive immune cells – namely the T cells – that carry out some similar functions as part of the type 2 immune response, so it was previously thought that the role of ILC2s may be redundant and could be easily taken over by the T cells.”

However, the recently published study has now disproved this theory. Using an animal model and state-of-the-art molecular methods such as single-cell sequencing, which allows scientists to zoom into individual cells and analyze their molecular state, they have shed light on the central functions of ILC2s. “A certain type of immune cells called eosinophils were not able to develop properly when ILC2s were absent,” explains Dr. Klose. “This relationship was previously unknown and came as a big surprise.” Eosinophils are involved in inflammatory processes in the tissue. The scientists also found that ILC2s have a major effect on the ability of epithelial cells to promote mucus production and expel parasites, such as worms, from the body. “The absence of ILC2s was clearly noticeable in our tests examining the immune response to worm infections. There was only limited mucus production in the tissue and the parasites could no longer be combated effectively,” says Dr. Klose, summarizing the results of the study.

In further experiments, the researchers examined the symptoms of allergic asthma and found that these improved when ILC2s were absent. “This could be a starting point for future studies aimed at developing potential allergy therapies,” says Dr. Klose. “With our study, we were able to show that group 2 innate lymphoid cells are essential cogs in the machinery of the immune system and cannot be replaced without compromising the immune response.” In future research projects, Dr. Klose and his team would like to investigate whether the innate lymphoid cells regulate other aspects of the immune response.

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Charite – Universitatsmedizin Berlin

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November 3, 2022
Sepsis and COVID-19 Patients Most at Risk Predicted with Genetic Model

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Newswise — A new model for understanding which patients with sepsis, Covid-19 and influenza have immune dysfunction and are more likely to suffer poor outcomes has been developed by researchers at the Wellcome Sanger Institute, the University of Oxford, Queen Mary University, Imperial College and their collaborators.

The study, published today (2 November 2022) in Science Translational Medicine, identified 19 genes that predict the way that the body’s immune system responds to sepsis, Covid-19 and influenza infection, and how immune response can go wrong in some individuals. The small number of genes used in the model paves the way for applying precision medicine techniques, such as prioritising individuals for particular interventions, to diseases like sepsis that have proven difficult to diagnose and treat.

Sepsis is caused by an ‘inappropriate‘ immune response to infection or injury, which can spread to the whole body. For reasons unknown, in sepsis immune response becomes overactive or underactive and causes damage to healthy cells, rather than just the source of infection. It is difficult to predict who will get sepsis, who will recover and who will have poor outcomes such as post-sepsis syndrome (PSS) and death. Globally, it is estimated that there are around 49 million sepsis cases and 11 million deaths each year¹.

Despite hundreds of clinical trials aimed at improving sepsis outcomes, there are currently no targeted treatments. Because sepsis can arise from myriad causes it is a highly variable disease, and positive results from some drug trials have not been reproducible in others.

It is thought that a stronger understanding of sepsis at the molecular level, so that patients can be classified according to the particular characteristics of their illness, is the key to greater success in identifying those at risk and developing effective treatments.

In this new study, researchers at the Wellcome Sanger Institute and the University of Oxford set out to develop a gene expression model for understanding which patients with sepsis are more likely to have particular responses and potentially poor outcomes.

This included 1,655 samples from sepsis patients collected as part of the UK Genomic Advances in Sepsis study, which were then sequenced at the Wellcome Sanger Institute to identify which genes were expressed. The resulting data were then combined with existing data from sepsis patients and healthy individuals.

Analysis of these data identified patterns of gene expression signifying an inappropriate immune response, allowing researchers to predict clinical outcomes from a group of just 19 genes.

Professor Julian Knight, a senior author of the study from the University of Oxford, said: “We urgently need better ways to understand what goes wrong with the immune system in response to infection to cause sepsis, a disease with devastating results for millions of people each year around the world. A fast, accurate test to predict who has a particular type of immune response to infection and is at greater risk from poorer outcomes in sepsis would help massively and now seems a genuine possibility.”

To gauge whether the 19-gene model could also be applied to other diseases, a machine-learning framework was developed to test it on sepsis, SARS-CoV-2 and influenza. The model was able to successfully predict an individual’s likelihood of poor outcomes for all three diseases.

Dr Eddie Cano-Gamez, an author of the study from the University of Oxford and Wellcome Sanger Institute, said: “Now that we have the ability to predict sepsis outcomes from just 19 genes, it’s crucial that as many researchers as possible can take advantage of this approach. To facilitate this we’ve created a code package to allow other researchers to run the model on their own data. This has been designed to be easy to use, no matter what technology was used to generate sample data.”

The next step for the researchers will be to understand more about the underlying immune dysfunction involved in sepsis and work with colleagues to develop biomarker-led clinical trials. The aim of this work would be to help target the most effective therapies at those who would benefit most, for example using the type of 19-gene model developed in this study.

Dr Emma Davenport, a senior author of the study from the Wellcome Sanger Institute, said: “Sepsis has long seemed an intractable problem because we simply didn’t understand the disease as well as we needed to. Similarly, the early stages of the Covid-19 pandemic highlighted the stress doctors were under, trying to treat patients without having solid information to help them identify those most at risk. Our model provides a level of detail that finally allows us to start applying precision medicine techniques to sepsis and improve outcomes for patients.”

ENDS

Notes to Editors:

¹For more information, see the UK Sepsis Trust website. In the UK, there are 48,000 sepsis deaths each year and two in five of those who survive suffer life-changing after-effects.

Publication:

Eddie Cano-Gamez et al. (2022). An immune dysfunction score for stratification of patients with acute infection based on whole blood gene expression. Science Translational Medicine. DOI: https://doi.org/10.1126/scitranslmed.abq4433

Funding:

This research was funded by the Medical Research Council, the NIHR Oxford Biomedical Research Centre and Wellcome.

Selected websites:

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The Wellcome Sanger Institute
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Wellcome Trust Sanger Institute

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November 2, 2022
By the next RSV season, the US may have its first vaccine | CNN

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CNN
—

It’s shaping up to be a severe season for respiratory syncytial virus infections – one of the worst some doctors say they can remember. But even as babies struggling to breathe fill hospital beds across the United States, there may be a light ahead: After decades of disappointment, four new RSV vaccines may be nearing review by the US Food and Drug Administration, and more than a dozen others are in testing.

There’s also hope around a promising long-acting injection designed to be given right after birth to protect infants from the virus for as long as six months. In a recent clinical trial, the antibody shot was 75% effective at heading off RSV infections that required medical attention.

Experts say the therapies look so promising, they could end bad RSV seasons as we know them.

And the relief could come soon: Dr. Ashish Jha, who leads the White House Covid-19 Response Task Force, told CNN that he’s “hopeful” there will be an RSV vaccine by next fall.

Charlotte Brown jumped at the chance to enroll her own son, a squawky, active 10-month-old named James, in one of the vaccine trials this summer.

“As soon as he qualified, we were like ‘absolutely, we are in,’ ” Brown said.

Babies have to be at least 6 months old to enter the trial, which is testing a vaccine developed at the National Institutes of Health – the result of decades of scientific research.

Brown is a pediatrician who cares for hospitalized children at Vanderbilt University Medical Center in Nashville, and she sees the ravages of RSV firsthand. A recent patient was in the back of her mind when she was signing up James for the study.

“I took care of a baby who was only a few months older than him and had had nine days of fever and was just absolutely pitiful and puny,” she said. Brown said his family felt helpless. “And I was like, ‘this is why we’re doing it. This single patient is why we’re doing this.’ “

Even before this year’s surge, RSV was the leading cause of infant hospitalizations in the US. The virus infects the lower lungs, where it causes a hacking cough and may lead to severe complications like pneumonia and inflammation of the tiny airways in the lungs called bronchiolitis.

Worldwide, RSV causes about 33 million infections in children under the age of 5 and hospitalizes 3.6 million annually. Nearly a quarter-million young children die each year from complications of their infections.

RSV also preys on seniors, leading to an estimated 159,000 hospitalizations and about 10,000 deaths a year in adults 65 and over, a burden roughly on par with influenza.

Despite this heavy toll, doctors haven’t had any new tools to head off RSV for more than two decades. The last therapy approved was in 1998. The monoclonal antibody, Synagis, is given monthly during RSV season to protect preemies and other high-risk babies.

The hunt for an effective way to protect against RSV stalled for decades after two children died in a disastrous vaccine trial in the 1960s.

That study tested a vaccine made with an RSV virus that had been chemically treated to render it inert and mixed with an ingredient called alum, to wake up the immune system and help it respond.

It was tested at clinical trial sites in the US between 1966 and 1968.

At first, everything looked good. The vaccine was tested in animals, who tolerated it well, and then given to children, who also appeared to respond well.

“Unfortunately, that fall, when RSV season started, many of the children that were vaccinated required hospitalization and got more severe RSV disease than what would have normally occurred,” said Steven Varga, a professor of microbiology and immunology at the University of Iowa, who has been studying RSV for more than 20 years and is developing a nanoparticle vaccine against the virus.

A study published on the trial found that 80% of the vaccinated children who caught RSV later required hospitalization, compared with only 5% of the children who got a placebo. Two of the babies who had participated in the trial died.

The outcomes of the trial were a seismic shock to vaccine science. Efforts to develop new vaccines and treatments against RSV halted as researchers tried to untangle what went so wrong.

“The original vaccine studies were so devastatingly bad. They didn’t understand immunology well in those days, so everybody said ‘oh no, this ain’t gonna work.’ And it really was like it stopped things cold for 30, 40 years,” said Dr. Aaron Glatt, an infectious disease specialist at Mount Sinai South Nassau in New York.

Regulators re-evaluated the guardrails around clinical trials, putting new safety measures into place.

“It is in fact, in many ways, why we have some of the things that we have in place today to monitor vaccine safety,” Varga said.

Researchers at the clinical trial sites didn’t communicate with each other, Varga said, and so the US Food and Drug Administration put the publicly accessible Vaccine Adverse Events Reporting System into place. Now, when an adverse event is reported at one clinical trial site, other sites are notified.

Another problem turned out to be how the vaccine was made.

Proteins are three-dimensional structures. They are made of chains of building blocks called amino acids that fold into complex shapes, and their shapes determine how they work.

In the failed RSV vaccine trial, the chemical the researchers used to deactivate the virus denatured its proteins – essentially flattening them.

“Now you have a long sheet of acids but no more beautiful shapes,” said Ulla Buchholz, chief of the RNA Viruses Section at the National Institutes of Allergy and Infectious Diseases.

“Everything that the immune system needs to form neutralizing antibodies that can block and block attachment and entry of this virus to the cell had been destroyed in that vaccine,” said Buchholz, who designed the RSV vaccine for toddlers that’s being tested at Vanderbilt and other US sites.

In the 1960s trial, the kids still made antibodies to the flattened viral proteins, but they were distorted. When the actual virus came along, these antibodies didn’t work as intended. Not only did they fail to recognize or block the virus, they triggered a powerful misdirected immune response that made the children much sicker, a phenomenon called antibody-dependent enhancement of disease.

The investigators hadn’t spotted the enhancement in animal studies, Varga says, because the vaccinated animals weren’t later challenged with the live virus.

“So of course, we require now extensive animal testing of new vaccines before they’re ever put into humans, again, for that very reason of making sure that there aren’t early signs that a vaccine will be problematic,” Varga said.

About 10 years ago, a team of researchers at the NIH – some of the same investigators who developed the first Covid-19 vaccines – reported what would turn out to be a pivotal advance.

They had isolated the structure of the virus’s F-protein, the site that lets it dock onto human cells. Normally, the F-protein flips back and forth, changing shapes after it attaches to a cell. The NIH researchers figured out to how freeze the F-protein into the shape it takes before it fuses with a cell.

This protein, when locked into place, allows the immune system to recognize the virus in the form it’s in when it first enters the body – and develop strong antibodies against it.

“The companies coming forward now, for the most part, are taking advantage of that discovery,” said Dr. Phil Dormitzer, a senior vice president of vaccine development at GlaxoSmithKline. “And now we have this new generation of vaccine candidates that perform far better than the old generation.”

The first vaccines up for FDA review will be given to adults: seniors and pregnant woman. Vaccination in pregnancy is meant to ultimately protect newborns – a group particularly vulnerable to the virus – via antibodies that cross the placenta.

Vaccines for children are a bit farther behind in development but moving through the pipeline, too.

Four companies have RSV vaccines for adults in the final phases of human trials: Pfizer and GSK are testing vaccines for pregnant women as well as seniors. Janssen and Bavarian Nordic are developing shots for seniors.

Pfizer and GSK use protein subunit vaccines, a more traditional kind of vaccine technology. Two other companies build on innovations made during the pandemic: Janssen – the vaccine division of Johnson & Johnson – relies on an adenoviral vector, the same kind of system that’s used in its Covid-19 vaccine, and Moderna has a vaccine for RSV in Phase 2 trials that uses mRNA technology.

So far, early results shared by some companies are promising. Janssen, Pfizer and GSK each appear effective at preventing infections in adults for the first RSV season after the vaccine.

In an August news release, Annaliesa Anderson, Pfizer’s chief scientific officer of Vaccine Research and Development, said she was “delighted” with the results. The company plans to submit its data to the FDA for approval this fall.

GSK has also wrapped up its Phase 3 trial for seniors. It recently presented the results at a medical conference, but full data hasn’t been peer reviewed or published in a medical journal. Early results show that this vaccine is 83% effective at preventing disease in the lower lungs of adults 60 and older. It appears to be even more protective – 94% – for severe RSV disease in those over 70 and those with underlying medical conditions.

“We are very pleased with these results,” Dormitzer told CNN. He said the company was moving “with all due haste” to get its results to the FDA for review.

“We’re confident enough that we’ve started manufacturing the actual commercial launch materials. So we have the bulk vaccine actually in the refrigerator, ready to supply when we are licensed,” he said.

Even as the company applies for licensure, GSK’s trial will continue for two more RSV seasons. Half the group getting the vaccine will be followed with no additional shots, while the other group will get annual boosters. The aim is to see which approach is most protective to guide future vaccination strategies.

Janssen’s vaccine for older adults appears to be about 70% to 80% effective in clinical trials so far, the company announced in December.

In a study on Pfizer’s vaccine for pregnant women published in the New England Journal of Medicine this year, the company reported that the mothers enrolled in the study made antibodies to the vaccine and that these antibodies crossed the placenta and were detected in umbilical cord blood just after birth.

The vaccines for pregnant women are meant to get newborns through their first RSV season. But not all newborns will benefit from those. Most maternal antibodies are passed to baby in the third trimester, so preemies may not be protected, even if mom gets the vaccine.

For vulnerable infants and those whose mothers decline to be vaccinated, Dr. Helen Chu, an infectious disease specialist at the University of Washington, says the long-acting antibody shot for newborns, called nirsevimab, should cover them for the first six months of life. She expects it to be a “game-changer.”

That shot, which has been developed by AstraZeneca, was recently recommended for approval in the European Union. It has not yet been approved in the United States.

The field is so close to a new approval that public health officials say they’ve been asked to study up on the data.

Chu, who is also a member of an RSV study group of the Advisory Committee on Immunization Practices, a panel that advises the US Centers for Disease Control and Prevention on its vaccine recommendations, says her group has started to evaluate the new vaccines – a sign that an FDA review is just around the corner.

No companies have yet announced that process is underway. FDA reviews can take several months, and then there are typically discussions and votes by FDA and CDC advisory groups before vaccines are made available.

“We’ve been working on this for several months now to start reviewing the data,” Chu said. “So I think this is imminent.”

Watching this year’s RSV season unfold, Brown, the pediatrician who enrolled her son in the vaccine trial for toddlers, says progress can’t come fast enough.

“The hospital is surging. We’re not drowning the way some states are. I mean, Connecticut, South Carolina, North Carolina, they’re really drowning. But our numbers are huge, and our services are so busy,” she says.

Brown says her son is mostly healthy. He doesn’t have any of the risks for severe RSV she sees with some of her patients, so she was happy to have a way to help others.

And while it’s far too early to say whether the vaccine James is helping to test will prove to be effective, the trial was unblinded last week, and Brown learned that her son was in the group that got the active vaccine, not the placebo

He has done well through this heavy season of illness, she says. The NIH-sponsored study they participated in is scheduled to be completed next year.

The vaccine, which is made with a live but very weak version of virus, is given through a couple of squirts up the nose, so there are no needles. The hardest part for squirmy James, she said, was being held still.

“If we can do anything to move science forward and help another child, like, sorry, James. You had to have your blood drawn, but it absolutely was worth it.”

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October 31, 2022
Identity Theft the Secret of the Cat Parasite’s Success

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Newswise — The parasite Toxoplasma is carried by a large portion of the global human population. Now a study led by researchers at Stockholm University shows how this microscopic parasite so successfully spreads in the body, for example to the brain. The parasite infects immune cells and hijacks their identity. The study is published in the scientific journal Cell Host & Microbe.

In order to fight infections, the various roles of immune cells in the body are very strictly regulated. Scientists have long wondered how Toxoplasma manages to infect so many people and animal species and spread so efficiently.

“We have now discovered a protein that the parasite uses to reprogram the immune system”, says Arne ten Hoeve, researcher at the Department of Molecular Biosciences, Wenner-Gren Institute at Stockholm University.

The study shows that the parasite injects the protein into the nucleus of the immune cell and thus changes the cell’s identity. The parasite tricks the immune cell into thinking it is another type of cell. This changes the gene expression and behavior of the immune cell. Toxoplasma causes infected cells which normally should not travel in the body to move very quickly and in this way the parasite spreads to different organs.

The phenomenon has been described as Toxoplasma turning immune cells into Trojan horses or wandering “zombies” that spread the parasite. The newly published study provides a molecular explanation for the phenomenon, and also shows that the parasite is much more targeted in its spread than previously thought.

“It is astonishing that the parasite succeeds in hijacking the identity of the immune cells in such a clever way. We believe that the findings can explain why Toxoplasma spreads so efficiently in the body when it infects humans and animals,” says Professor Antonio Barragan, who led the study, which was carried out in collaboration with researchers from France and the USA.

The work is published in the scientific journal Cell Host & Microbe.
The Toxoplasma effector GRA28 promotes parasite dissemination by inducing dendritic cell-like migratory properties in infected macrophages. Arne L. ten Hoeve, Laurence Braun, Matias E. Rodriguez, Gabriela C. Olivera, Alexandre Bougdour, Lucid Belmudes, Yohann Couté, Jeroen P.J. Saeij, Mohamed-Ali Hakimi, Antonio Barragan DOI: 10.1016/j.chom.2022.10.001

About the parasite Toxoplasma and the disease toxoplasmosis:

Toxoplasmosis is probably the most common parasitic infection in humans globally. Toxoplasma also infects many animal species (zoonosis), including our pets. The WHO has estimated that at least 30% of the world’s human population is a carrier of the parasite. Studies indicate that 15-20% of the Swedish population carry the parasite (the vast majority without knowing it). The incidence is higher in several other European countries.

Felines, not just domestic cats, have a special place in the life cycle of Toxoplasma: it is only in the cat’s intestine that sexual reproduction takes place. In other hosts, for example humans, dogs or birds, reproduction takes place by the parasite dividing.

Toxoplasma is spread through food and contact with cats. In nature, the parasite spreads preferentially from rodents to cats to rodents and so forth. The parasites are “sleeping” in the rodent’s brain and when the cat eats the mouse, they multiply in the cat’s intestine and come out via the feces. The parasite ends up in the vegetation and when the rodent eats the vegetation it becomes infected. Humans become infected through meat consumption or through contact with cats, specifically cat feces.

The parasite causes the disease toxoplasmosis. When a person is infected for the first time, mild flu-like symptoms occur that can resemble a cold or a flu. After the first infection phase, the parasite transitions to a “sleeping” stage in the brain and begins a chronic silent infection that can last for decades or for life. The chronic infection usually causes no symptoms in healthy individuals. Toxoplasma can, however, cause a life-threatening brain infection (encephalitis) in people with a weakened immune system (HIV, organ transplant recipients, after chemotherapy) and can be dangerous to the fetus during pregnancy. Eye infections can occur in otherwise healthy individuals.

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Stockholm University

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October 28, 2022
Bobby Brooke Herrera Joins Rutgers Global Health Institute as Principal Faculty Member

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Newswise — Research scientist Bobby Brooke Herrera, renowned for developing tools to accelerate diagnosis and treatment of infectious diseases such as COVID-19, has joined Rutgers Global Health Institute.

Herrera, a Rutgers Presidential Faculty Scholar and an assistant professor of global health at the institute, conducts multidisciplinary research on epidemic viruses and infectious diseases and holds joint appointments in the Division of Allergy, Immunology and Infectious Diseases in the Department of Medicine and at the Child Health Institute of New Jersey. Both are part of Rutgers Robert Wood Johnson Medical School. Herrera is known for his bench-to-bedside translational research. His laboratory at Rutgers focuses on understanding adaptive immunity against globally relevant pathogens that cause lethal human diseases and for which there are limited options for treatment or vaccination.

He has developed diagnostic testing related to the SARS-CoV-2 virus and COVID-19 disease, the Zika virus, and the rare but often deadly Ebola virus disease. Collaborating internationally with research scientists in Brazil, Nigeria and Senegal, his academic and industry work has received more than $9 million in grant funding, including support from the National Institutes of Health and the Bill & Melinda Gates Foundation as well as venture capital financing.

Disease outbreak preparedness and response motivate and drive Herrera’s research, which incorporates approaches in epidemiology, immunology, molecular biology and virology. He seeks to uncover new knowledge about human immune responses that will spur fundamental advancements in disease diagnostic capabilities and vaccine design. Herrera is studying asymptomatic viral infections, which occur when an individual infected with a virus develops little to no symptoms of disease, to better understand the human antibody and T cell responses in such instances.

“I hope that my research group at Rutgers will contribute to a foreseeable expansion of vaccines or therapeutics for infectious diseases in the decades to come, with particular focus on deciphering at the molecular level what may make some antibodies or T cells more effective than others,” Herrera said. “There are many hypotheses as to why that happens and why some people develop disease symptoms and some remain asymptomatic. It could be genetics, immune status, environmental factors or reasons related to the virus itself. These are questions I’m interested in pursuing in my academic lab. The knowledge we produce can lead to better, more personalized diagnostics as well as more potent therapeutics for these viruses.”

Herrera has investigated various dynamics of asymptomatic human infections by mosquito-borne viruses, including the flaviviruses Zika and dengue as well as the alphavirus chikungunya. His findings indicated that human transmission of Zika and dengue viruses in Nigeria and Senegal occurred in absence of robust disease outbreaks. In Brazil, he tested a diagnostic tool he developed to distinguish between infections by distinct virus strains. Also in Nigeria, Herrera’s research demonstrated that individuals who experienced asymptomatic infections by Ebola virus could produce T cell responses that were greater in magnitude when compared with survivors of severe Ebola virus disease.

Herrera, originally from New Mexico, received a doctoral degree in biological sciences in public health at Harvard University and performed postdoctoral training at Harvard Medical School. Since 2019, he served as a visiting scientist at the Harvard T.H. Chan School of Public Health. He cofounded two biotechnology startup companies and was named to the “Forbes 30 under 30” list for health care in 2020.

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Rutgers University-New Brunswick

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October 28, 2022
Study Identifies Key T Cells for Immunity Against Fungal Pneumonia

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Newswise — Researchers at the University of Illinois College of Veterinary Medicine have demonstrated in a mouse model that a specific type of T cell, one of the body’s potent immune defenses, produces cytokines that are necessary for the body to acquire immunity against fungal pathogens. This finding could be instrumental in developing novel, effective fungal vaccines.

Despite vaccines being hailed as one of the greatest achievements of medicine, responsible for controlling or eradicating numerous life-threatening infectious diseases, no vaccines have been licensed to prevent or control human fungal infections.

This lack proved especially deadly during the COVID-19 pandemic. In countries where steroids were widely used to suppress inflammation of the lungs, COVID-19 patients with preexisting conditions such as uncontrolled diabetes showed a greater likelihood of developing lethal fungal infections.

T Cells Could Produce Protective or Pathological Response

“A particular type of T cell [T_H17 cells] that expresses GM-CSF [granulocyte-macrophage colony-stimulating factor] was linked to greater severity of illness in people infected with the virus that causes COVID-19,” said Dr. Som Nanjappa, an assistant professor of immunology at the University of Illinois.

“Our study shows that IL-17A⁺ CD8⁺ T cell (Tc17), which also expresses GM-CSF, is necessary for mediating fungal vaccine immunity without instigating hyperinflammation. So clearly, the antigen specificity of T cells—whether they target viral vs. fungal or bacterial pathogens—has a huge impact on whether they play a protective or detrimental role.”

The article, “GM-CSF+ Tc17 cells are required to bolster vaccine immunity against lethal fungal pneumonia without causing overt pathology,” appeared in Cell Reports on October 25. Dr. Nanjappa’s coauthors on the study are Srinivasu Mudalagiriyappa, a former graduate student now a scientist with Insmed Incorporated, a global biopharmaceutical company focused on serious and rare diseases; Jaishree Sharma, a graduate student in the Department of Pathobiology; and Miranda D. Vieson, a Clinical Associate Professor in the Department of Pathobiology as well as a boarded veterinary pathologist in the college’s Veterinary Diagnostic Laboratory.

T Cells for Fungal Vaccine Immunity

In the study, colonies of mice were given an experimental fungal vaccine. The mice were then exposed to virulent fungal pathogen to cause lethal pulmonary infection. Researchers could determine the necessity of GM-CSF⁺ Tc17 cells to mediate vaccine immunity. Further, they found that IL-1 and IL-23 cytokines are necessary for eliciting GM-CSF⁺ Tc17 cells to vaccine. While IL-23 is dispensable for the long-term memory homeostasis of these cells, it is essential for vaccine immunity against pulmonary fungal infection.

This study identifies a beneficial subset of T cells for fungal vaccine immunity that bolsters efforts to develop a vaccine platform containing suitable adjuvants to potentiate such a T cell subset.

“In line with this, we have identified a functional phenotypic marker that could be targeted to enhance this subset to augment vaccine efficacy,” said Dr. Nanjappa. He recently received NIH-R01 funding to pursue this strategy for a fungal vaccine.

Read the study online: https://doi.org/10.1016/j.celrep.2022.111543

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University of Illinois at Urbana-Champaign

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October 25, 2022
New machine-learning technique for classifying key immune cells has implications for a suite of diseases

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Newswise — Eesearchers from Trinity College Dublin have developed a new, machine learning-based technique to accurately classify the state of macrophages, which are key immune cells. Classifying macrophages is important because they can modify their behaviour and act as pro- or anti-inflammatory agents in the immune response. As a result, the work has a suite of implications for research and has the potential to one day make major societal impact.

For example, this new approach could be of use to drug designers looking to create therapies targeting diseases and auto-immune conditions such as diabetes, cancer and rheumatoid arthritis – all of which are impacted by cellular metabolism and macrophage function.

Because classifying macrophages allows scientists to directly distinguish between macrophage states – based only on their metabolic response under certain conditions – this new information could be used as a diagnosis tool, or to highlight the role of a particular cell type in a disease environment.

The landmark research, which used human macrophages in experiments, was led by Michael Monaghan, Associate Professor in Biomedical Engineering at Trinity. The work brought together biomedical engineers, computer scientists and immunologists and has just been published in leading journal eLife. Professor Monaghan comments:

“Currently, there are no other methods that employ artificial intelligence-based, machine learning approaches to macrophage classification. A number of different techniques are currently used to classify macrophages, but all of these have significant drawbacks.

“Our method uses a 2-photon fluorescence lifetime imaging microscope (2P-FLIM), which is unique to Trinity and to Ireland. 2P-FLIM does not require sample pre-treatment, can be used to follow changes in metabolism non-invasively and in real-time – which opens the door to tracking disease progression and/or physiological response to therapies — and it also requires a lower number of cells compared with conventional techniques.”

Nuno Neto, PhD Candidate in the School of Engineering, added:

“It is becoming increasingly clear that to solve many of society’s greatest problems, we need to take multi-disciplinary approaches to harness the expertise of people working in different fields.

“Trinity is rightly known as a leader in immunometabolism research, with many of our scientists focusing on how it regulates immune cell response, and how immune cell metabolism is impacted in diseases. This study benefits from that expertise, but also bridges the use of advanced computer science approaches and utilises an advanced microscope from the Biomedical Engineering Department with a regime never reported previously. It thus serves as a prime example of inter-departmental collaboration in a multidisciplinary field.”

Nuno Neto’s Doctoral Studies are supported by a Trinity College Dublin Provost’s PhD Award and Professor Monaghan is a Funded Investigator in the Science Foundation Ireland (SFI) Centres AMBER and CÚRAM. Trinity’s FLIM Core Unit directed by Professor Monaghan was established using an SFI Infrastructure Programme: Category D Opportunistic Funds Call.

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Trinity College Dublin

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October 18, 2022
Viral infections are less frequent but more severe in people with Down syndrome due to oscillating immune response

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Newswise — Individuals with Down syndrome have less-frequent viral infections, but when present, these infections lead to more severe disease. New findings publishing on October 14 in the journal Immunity show that this is caused by increased expression of an antiviral cytokine type I interferon (IFN-I), which is partially coded for by chromosome 21. Elevated IFN-I levels lead to hyperactivity of the immune response initially, but the body overcorrects for this to reduce inflammation, leading to increased vulnerability later in the viral attack.

“Usually too much inflammation means autoimmune disease, and immune suppression usually means susceptibility to infections,” says senior study author Dusan Bogunovic of the Icahn School of Medicine at Mount Sinai. “What is unusual is that individuals with Down syndrome are both inflamed and immunosuppressed, a paradox of sorts. Here, we discovered how this is possible.”

Down syndrome is typically caused by triplication of chromosome 21. This syndrome affects multiple organ systems, causing a mixed clinical presentation that includes intellectual disability, developmental delays, congenital heart and gastrointestinal abnormalities, and Alzheimer’s disease in older individuals.

Recently, it has become clear that atypical antiviral responses are another important feature of Down syndrome. Increased rates of hospitalization of people with Down syndrome have been documented for influenza A virus, respiratory syncytial virus, and severe acute respiratory syndrome due to coronavirus (SARS-CoV-2) infections.

While people with Down syndrome show clear signs of immune disturbance, it has yet to be elucidated how a supernumerary chromosome 21 leads to dysregulation of viral defenses. To address this knowledge gap, the researchers compared fibroblasts and white blood cells derived from individuals with and without Down syndrome, at both the mRNA and protein levels. They focused on the potent antiviral cytokine IFN-I receptor subunits IFNAR1 and IFNAR2, which are located on chromosome 21.

The researchers found that increased IFNAR2 expression was sufficient for the hypersensitivity to IFN-I observed in Down syndrome, independent of trisomy 21. But subsequently, the hyper-active IFN-I signaling cascade triggered excessive negative feedback via a protein called USP18, which is a potent IFNAR negative regulator. This process, in turn, suppressed further responses to IFN-I and antiviral responses. Taken together, the findings unveil oscillations of hyper- and hypo-responses to IFN-I in Down syndrome, predisposing to both lower incidence of viral disease and increased infection-related morbidity and mortality.

“We have a lot more to do to completely understand the complexities of the immune system in Down syndrome,” says first author Louise Malle of the Icahn School of Medicine at Mount Sinai. “We have here, in part, explained the susceptibility to severe viral disease, but this is only the tip of the iceberg.”

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Cell Press

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October 14, 2022
UCLA Fielding School of Public Health-led research demonstrates the importance of influenza vaccination globally

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Newswise — LOS ANGELES (Oct. 5, 2022) – An international team of researchers has demonstrated that among patients hospitalized for influenza, those who were vaccinated had less severe infections, including reducing the odds for children requiring admittance to an intensive care unit by almost half.

In addition, the researchers found that deaths among hospitalized adults, 65 or older, who had been vaccinated were 38% lower compared to those who had not been vaccinated.

“A common complaint about influenza vaccine is that they are typically 40-60% effective against infection – or the ‘what’s the point?’ complaint. So it is important to note that although everyone in this study was hospitalized, vaccinated individuals were less likely to be severely ill or die, suggesting that you are likely to have far less severe consequences if vaccinated,” said Dr. Annette Regan, UCLA Fielding School of Public Health assistant professor of epidemiology and lead author of the peer-reviewed research, published this week in the October edition of The Lancet Infectious Diseases. “This is an important point, especially in light of the upcoming influenza season coupled with ongoing COVID-19 activity, both this season and into the future.”

Globally, influenza contributes to 9.5 million hospitalizations, 81.5 million hospital days, and 145,000 deaths each year. Vaccination offers the best method of preventing influenza illness, reducing illness in the general population by 40–60%, experts say.

Specifically, The Lancet analysis found that three groups routinely targeted for influenza vaccination experiences less severe illness. Children who had received only part of their first series of influenza vaccines had 36% lower chances of being admitted to an intensive care unit (ICU), and children who had fully completed their first series of influenza vaccines had 48% lower chances of admission to ICU compared to unvaccinated children, the researchers found.

The study – “Severity of influenza illness associated with seasonal influenza vaccination among hospitalized patients in four South American countries” – is the product of an international team of researchers from the United States, Argentina, Brazil, Chile, and Paraguay, and drew on data from all four South American countries over a period of seven years. Data were obtained through the Network for the Evaluation of Vaccine Effectiveness in Latin America and the Caribbean, influenza (REVELAC-i) which is coordinated by the Pan American Health Organization (PAHO).

“Although several studies have reported drops in influenza illness following influenza vaccination, the results have focused predominantly on adults in the United States, and this study aimed to evaluate the severity of influenza illness by vaccination status in a broad range of age groups, and across multiple South American countries,” said Dr. Marta Von Horoch, a co-author who serves as coordinator of the National Immunization Program in Paraguay. “We were very pleased to work with our partners in the U.S. and across the continent, and these findings demonstrate, quite clearly, the importance of influenza vaccination for children and adults, no matter where they live.”

The study – the first-ever on this scale in South America – examined influenza-related hospitalization rates and outcomes across all four countries from 2013-19. Specifically, the analysts reviewed the outcomes for some 2,747 patients hospitalized with confirmed influenza virus infection, in three age groups – children aged 6–24 months, adults aged 18–64 years, and adults aged 65 years or older.

Given the reality that vaccination rates have fallen, in the U.S. and globally during the COVID-19 pandemic, including among children, the findings should help make clear the benefits of timely, pro-active immunization campaigns to the public, the researchers said.

“With influenza season approaching this winter and influenza vaccines now available, these results highlight the importance of getting vaccinated for flu for anyone six months of age or older – as CDC recommends,” Regan said. “It is critical that healthcare providers and the public understand the risks of missing out on vaccinations – it is so much better to prevent a serious illness than to suffer through it, for the patient and everyone in their community.”

PRINCIPAL INVESTIGATOR: Regan, also a faculty affiliate with UCLA’s Bixby Center on Population and Reproductive Health, has taught at the university since 2019. She earned her PhD from the University of Western Australia in 2016. As part of her doctoral work, Regan established one of the largest population-based cohorts to investigate the safety of influenza vaccination in pregnancy and Australia’s first rapid surveillance system for monitoring the safety of vaccines given during pregnancy. She is also currently leading a large U.S. study on COVID-19 vaccination during pregnancy. Regan has served as an epidemiologist with the Western Australia Department of Health (2013-16) and Epidemiologist for the U.S. Centers for Disease Control and Prevention (2007-11). She is also on faculty at the University of San Francisco’s School of Nursing and Health Professions.

METHODS: Using surveillance data from four South American countries, the team examined indicators of severity of illness among influenza-associated hospitalizations, including length of hospital stay, admission to ICU, and death in hospital. Data collection conformed to a common protocol, reducing heterogeneity in measurements. As a result, the researchers were able to evaluate the health effects associated with influenza vaccination in a large sample of three priority groups, including children aged 6–24 months. The large sample size also enabled analyses by influenza virus subtype and by number of pre-existing health conditions. The results for each group was subjected to separate statistical analyses.

FUNDING: This work was supported by a grant from the U.S. Centers for Disease Control and Prevention (CDC) through cooperative agreements with the Pan American Health Organization and the World Health Organization.

CITATION: Regan A, Arriola CS, Couto P, et al. Severity of influenza illness associated with seasonal influenza vaccination among hospitalised patients in four South American countries, 2013–19: a surveillance-based cohort study. Lancet Infectious Diseases, S1473-3099(22)00493-5.

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_{The UCLA Fielding School of Public Health, founded in 1961, is dedicated to enhancing the public’s health by conducting innovative research, training future leaders and health professionals from diverse backgrounds, translating research into policy and practice, and serving our local communities and the communities of the nation and the world. The school has 761 students from 26 nations engaged in carrying out the vision of building healthy futures in greater Los Angeles, California, the nation and the world.}

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October 5, 2022
The COVID pandemic is over? Not quite there, say scientists

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Newswise — In widely covered remarks during an interview with 60 Minutes correspondent Scott Pelley, President Biden claimed, “the pandemic is over.” Biden elaborated, adding, “we still have a problem with COVID, we’re still doing a lot of work on it, but the pandemic is over. If you noticed, no one’s wearing masks, everybody seems to be in pretty good shape. And so I think it’s changing, and I think this is a perfect example of it.”

According to the Washington Post, Biden’s remarks caught some senior officials off guard, particularly since the U.S. government has started its fall vaccination campaign. Although the Centers for Disease Control and Prevention announced more relaxed COVID-19 guidelines last month, the agency specifically said that the pandemic was not over in a press release issued on August 11th. Therefore, this statement has earned a rating of “Half True.”

With the rollout of boosters of life-saving vaccines, new treatments, and a large population already infected, the U.S. is in a less vulnerable place than it was in 2020. However, the death toll, while lower than before, is still at around 400 deaths per day from COVID-19 in the U.S. Many health experts say we’re not out of the woods yet.

“Saying that the pandemic is over has much larger and more serious ramifications, it means we take away resources allocated by Congress and other agencies. We must be careful about saying it is over. We still need resources to continue vaccination and to address vaccine hesitancy.” says Bernadette Boden-Albala, MPH, DrPH, Founding Dean and Director of the UCI Program in Public Health.

The end of masking restrictions and relaxing of other major guidelines has given many Americans a sense of moving on from the national health crisis that has festered for more than two years. Biden’s remarks, though perhaps an oversimplification, reflect national sentiment. However, COVID-19 is still very much evident in our U.S. population, and will likely continue for the foreseeable future.

“This is in great part due to human behaviors and motivations,” says Halkitis, “including subpar vaccination uptake, which continues to place all of us at risk for infection.”

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Newswise

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September 26, 2022
A New T-Cell activation assay based on Hyris qPCR Technology marks a disruptive approach for the detection of SARS-CoV-2 specific cellular immunity

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A scientific paper recently published in Nature Biotechnology reveals new research regarding how we track and monitor T-cell patients’ immunity to SARS-CoV-2, leveraging the unique characteristics of Hyris System™. The study results from a joint effort of an international research team from the Icahn School of Medicine at Mount Sinai, Singapore Duke-NUS Medical School, laboratory diagnostic service providers Synlab, and Hyris.

Press Release
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Jun 15, 2022

LONDON, June 15, 2022 (Newswire.com)
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With over 460 million global cases thus far, 6 million of which have resulted in death, the COVID-19 pandemic from SARS-CoV-2 proved to be a dire health crisis on a global scale. In this concerning scenario, the unprecedented effort by the international scientific community is even more remarkable and led – in record time – to the deployment of mRNA and viral vector-based vaccines. With more than 10 billion total vaccine doses administered worldwide, vaccination campaigns have already started to attenuate this global crisis. In order to maximize vaccine effectiveness, the efficacy and duration of protective immunity will need to be systematically assessed and monitored as widely as possible.

A team of internationally renowned medical scientists recently published a related paper in Nature Biotechnology, addressing the efficacy and sensitivity of a new type of assay to detect SARS-CoV-2 cellular immunity.

“To date, antibody tests have been the typical, if not the only clinical endpoints commonly used to measure the immune response to SARS-CoV-2,” explains Antonio Bertoletti, Professor at Duke-NUS Medical School. “Both the humoral (antibodies) and cellular immune response act in coordination to achieve long-term protection from viral infections. Antibodies are important for preventing infection, protecting the body from disease, while cellular immunity is essential to eliminate virus-infected cells, thus helping to fight the disease itself,” concludes Professor Bertoletti.

Therefore, according to the study, measuring the T-cells’ response is a new disruptive approach to fighting SARS-CoV-2. An individual negative to an antibody test could still be protected thanks to responsive T-cells.

This new study thus shows the relevance of a quantitative PCR approach to T-cell testing, thanks to the joint effort with SYNLAB, one of the world’s leading providers of laboratory diagnostic services, and Hyris, a global biotech company focused on AI-powered genetic analysis.

The research leveraged Hyris’ signature technology, the disruptive Hyris System™.

“These highly scalable screening methods will be particularly important, to monitor the magnitude and duration of functional cellular immunity towards emerging variants, thus helping to prioritize revaccination strategies in vulnerable populations,” states Cristina Lapucci, Head of Genetics and Molecular Biology at SYNLAB Italy.

“We have been very committed to putting our System at such prestigious partners’ service,” says Stefano Lo Priore, Founder and CEO at Hyris. “Many medical institutions worldwide already adopted our technology, embracing the unprecedented simplicity, connectivity, and scalability of the Hyris System^TM.”

The rapid deployment of SARS-CoV-2 vaccines to a large proportion of the population now suggests new approaches to measure the duration of the immune response, and the potential need for vaccine boosters should be evaluated.

“The assays used in our study rely on the quantification of CXCL10 mRNA after incubation of whole blood with SARS-CoV-2 specific peptides. The levels of induced CXCL10 transcripts correlate robustly with the IFN-gamma produced by activated antigen-specific T cells, serving as a proxy to detect cellular immunity in COVID-19 recovered and SARS-CoV-2 vaccinated subjects,” points out Ernesto Guccione, PhD, Professor of Oncological Sciences, and Pharmacological Sciences, at Icahn Mount Sinai.

“This is particularly important after the emergence of SARS-CoV-2 variants like Omicron that evade most of the neutralizing ability of antibodies, but not that of T-cells,” continues Megan Schwarz, a graduate student at Icahn School Mount Sinai and first author of the manuscript. “Precise measurement of cellular responses underlying virus protection, therefore, represents a crucial parameter of immune defence.”

“The solutions already present on the market are usually performed based on the traditional fluorescence methodologies typically used in the immunological domain,” adds Jordi Ochando, PhD, Assistant Professor of Oncological Sciences, Medicine (Nephrology), and Pathology, Molecular, and Cell-Based Medicine at Icahn Mount Sinai. “This research demonstrates that CXCL10 mRNA expression confirms data obtained with traditional methods (i.e., ELISpot) compared with naïve, COVID-19 convalescent and SARS-CoV-2 vaccinated subject,” he concludes.

This study could prove a key solution to further support the scientific community playing a strategic role in facing this global challenge.

Contact a Hyris expert to discover how to perform beyond your current diagnostic capability at info@hyris.net.

Source: Hyris

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June 15, 2022