Killer T cells that 'remember' past infection boost immune response to COVID-19 variants: Study- Technology News, Firstpost

Killer T cells that ‘remember’ past infection boost immune response to COVID-19 variants: Study

  • March 31, 2021

The killer T cell responses remained largely intact, as per the study, and could recognize virtually all mutations in the variants.

Killer T cells that 'remember' past infection boost immune response to COVID-19 variants: Study

In this image, killer T cells surround a cancer cell. T-cells can ‘remember’ past infections and kill pathogens if they reappear. They are thought to have a big influence on how long people remain resistant to infection and disease. Image: NIH

The emergence of coronavirus variants has provoked concern about their impact on the effectiveness of vaccines, and whether people who were previously infected might be more susceptible to reinfection. But in welcome news, a new study on Tuesday showed that a key player in the immune response, called the “killer T cell,” remained mostly unaffected. The finding is encouraging because although these white blood cells are not a first line defense against infection, they can help prevent severe disease. Scientists at the National Institutes of Health and Johns Hopkins University analyzed blood samples from 30 people who had contracted and recovered from COVID-19 prior to the emergence of variants. They published their findings in Open Forum Infectious Diseases, an Oxford University Press journal.

The team wanted to know whether these cells, known by their technical name “CD8+ T cells,” could still recognize three variants of SARS-CoV-2: B.1.1.7, first found in Britain, B.1.351, identified in South Africa, and B.1.1.248, first seen in Brazil.

What makes each of these variants unique is the mutations they carry, especially in a region of the virus’ spike protein, structures that stud its surface and allow it to invade cells.

It has already been shown that mutations to this region of the spike protein make some variants less recognizable to neutralizing antibodies — infection fighting proteins produced by the immune system’s B cells.

This seems to be particularly true, for instance, of B.1.351, according to research on the impact of current generation COVID-19 vaccines.

Neutralizing antibodies are custom-made to fit an antigen, or a specific structure of a pathogen. In the case of the coronavirus , this is the spike protein, which the antibodies bind to, preventing the virus from infecting cells.

Killer T cells, on the other hand, look for telltale signs of cells that have already been infected with pathogens they have previously encountered, and then kill those cells.

In the new study, the researchers found that the killer T cell responses remained largely intact and could recognize virtually all mutations in the variants studied.

The researchers noted that larger studies are needed to confirm the results, but said that it nevertheless demonstrated that killer T cells are less susceptible to mutations in the coronavirus than neutralizing antibodies are.

Antibodies are still important to prevent infection in the first place — and the reduced efficacy of vaccines to the variants seems to be evidence of this.

But a killer T cell response that kicks in later and aids in clearing off the disease, helps explain why the vaccines seem to be able to prevent severe disease and hospitalization, even though their efficacy at stopping infection by variants is reduced.

Killer T cells that 'remember' past infection boost immune response to COVID-19 variants: Study- Technology News, Firstpost

Killer T cells that ‘remember’ past infection boost immune response to COVID-19 variants: Study- Technology News, Firstpost

  • March 31, 2021

The emergence of coronavirus variants has provoked concern about their impact on the effectiveness of vaccines, and whether people who were previously infected might be more susceptible to reinfection. But in welcome news, a new study on Tuesday showed that a key player in the immune response, called the “killer T cell,” remained mostly unaffected. The finding is encouraging because although these white blood cells are not a first line defense against infection, they can help prevent severe disease. Scientists at the National Institutes of Health and Johns Hopkins University analyzed blood samples from 30 people who had contracted and recovered from COVID-19 prior to the emergence of variants. They published their findings in Open Forum Infectious Diseases, an Oxford University Press journal.

The team wanted to know whether these cells, known by their technical name “CD8+ T cells,” could still recognize three variants of SARS-CoV-2: B.1.1.7, first found in Britain, B.1.351, identified in South Africa, and B.1.1.248, first seen in Brazil.

What makes each of these variants unique is the mutations they carry, especially in a region of the virus’ spike protein, structures that stud its surface and allow it to invade cells.

It has already been shown that mutations to this region of the spike protein make some variants less recognizable to neutralizing antibodies — infection fighting proteins produced by the immune system’s B cells.

This seems to be particularly true, for instance, of B.1.351, according to research on the impact of current generation COVID-19 vaccines.

Neutralizing antibodies are custom-made to fit an antigen, or a specific structure of a pathogen. In the case of the coronavirus, this is the spike protein, which the antibodies bind to, preventing the virus from infecting cells.

Killer T cells, on the other hand, look for telltale signs of cells that have already been infected with pathogens they have previously encountered, and then kill those cells.

In the new study, the researchers found that the killer T cell responses remained largely intact and could recognize virtually all mutations in the variants studied.

The researchers noted that larger studies are needed to confirm the results, but said that it nevertheless demonstrated that killer T cells are less susceptible to mutations in the coronavirus than neutralizing antibodies are.

Antibodies are still important to prevent infection in the first place — and the reduced efficacy of vaccines to the variants seems to be evidence of this.

But a killer T cell response that kicks in later and aids in clearing off the disease, helps explain why the vaccines seem to be able to prevent severe disease and hospitalization, even though their efficacy at stopping infection by variants is reduced.

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For The Biome Delivers Highly Anticipated Formulation of Cistus Incanus to North American Market, Mediterranean Herb Clinically Proven to Strengthen Immune Response in 2 Hours

  • March 30, 2021

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Industry Icon Paul Schulick Unveils Immune Therapy Cistus+ Infusion with Extraordinary Combination of Protective Compounds

DUMMERSTON, VT, March 30, 2021 (GLOBE NEWSWIRE) — For The Biome, founded by industry innovator and master herbalist Paul Schulick, has launched Immune Therapy Cistus+ Infusion, a groundbreaking formula that’s clinically proven to strengthen your immune response within 2 hours.*  The headline ingredient is the Mediterranean super-herb, Cistus incanus. This is the first time that a cistus formulation will be widely available to the North American market.    

Schulick, who has created some of the most iconic natural products of the last 40 years, credits Cistus incanus as the most important discovery he has yet encountered in the natural world. Along with a potent dose of cistus, Immune Therapy Cistus+ Infusion features synergistic botanicals that help amplify its clinically proven efficacy, and includes vitamin C-rich rosehip, immunomodulating blackcurrant leaf and chaga mushroom. The formula is supported by pre-clinical and clinical results showing that within 1-2 hours, immune cells were activated to have a strengthened response to threats. Immune Therapy Cistus+ Infusion has the potential to become the standard for building strength and resilience of the immune system amidst modern health challenges. 

Cistus Incanus, A Mediterranean SuperHerb with a Rich History: 

Also known as pink rockrose, Cistus incanuss distinct character is a rare combination of protective compounds, making it one of the most beneficial herbs ever evaluated. Possessing at least 32 known polyphenols, Cistus incanus has been revered for centuries as a highly beneficial, cleansing, and immune-supportive herb. Modern clinical studies confirm traditional use for this immunomodulating effects and support of overall well-being.  

“In my entire career, I’ve yet to see another herb deliver such powerful results,” says Schulick, who recently left the corporate world to independently continue his work in redefining the supplement industry’s immune category with science-backed herbals. “Greek farmers and monks have an ancestral knowledge of Cistus incanus, which no doubt has contributed to the Mediterranean being known as a longevity zone,” says Schulick. “The people of the Halkidiki peninsula in Greece have been drinking Cistus incanus as tea for thousands of years. To this day, people in this region are known for living beyond the age of 100 more than in other parts of the world and Cistus incanus is, in my opinion, one of the key reasons why.”  

The plant itself thrives under profoundly adverse conditions, growing in a harsh Mediterranean ecosystem and enduring drought, intense sun exposure, and high temperatures. This leads the plant to produce high levels and a unique combination of polyphenols to protect itself. Schulick used his extensive sourcing expertise to locate, test, accentuate, and validate potent ingredients in order to create the most phytoactive-rich cistus formulation available. In an industry where adulteration is common, Schulick wants his customers to be confident knowing they have the “best of the best,” with ingredients validated through third-party testing to ensure the highest quality available.   

Drinking Cistus A Cascade of Positive Events: 

Immune Therapy Cistus+ Infusion comes in jumbo, eco-friendly steeping bags for easy preparation. Upon drinking the infusion, the mouth is bathed with a unique array of protective actives. There are many benefits of drinking an infusion, as it allows the herbs to directly contact the immune tissues in your mouth and throat and quickly absorb for faster results. Biotransformed phytoactives immediately work with your microbiome to enhance your gut barrier with short-chain fatty acids and help signal a healthy immune response. The formula does not focus on “boosting” your immune system, as this may not have a desirable effect in your body. Instead, Immune Therapy supports what Schulick has termed a “wiser immune system.” A wiser immune system can make a more precise, effective, and balanced immune response that is better able to respond to challenges. 

Immune Therapy Cistus+ Infusion comes in a refillable jar with 10 infusion bags. Net Weight: 2.1oz (60g). Suggested use: Drink one 12-oz cup for daily support and fast-acting protection. Price: $29.95. Available now at Forthebiome.com. 

About For The Biome 

For The Biome’s mission is to deliver solutions for body, mind, and microbiome that build strength and resilience amidst modern health challenges. Founder Paul Schulick is renowned for pioneering whole-food fermented vitamins integrated with science-backed herbals. Bolstered by his track record of consistently launching #1-selling innovations at New Chapter, which he founded in 1982 and sold to P&G in 2012, Schulick has once again shifted the paradigm by redefining the immune category with time-tested ingredients that are new to market. For The Biome’s three immune products—Immune Therapy Cistus+ Infusion, Stress Therapy, and Gut-Lung Therapy—are formulated in Vermont and launched March 2021. To learn more, visit Forthebiome.com.

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. The information provided does not constitute medical advice and should not take the place of consulting a physician. This information does not and should not replace treatment from a medical professional. If you need medical advice or assistance, you should consult a physician. 


SMART develops rapid deterministic lateral displacement assay to assess immune response

SMART develops rapid deterministic lateral displacement assay to assess immune response

  • March 25, 2021

IMAGE

IMAGE: A closeup of the microfluidic DLD assay chip with the Singapore $1 coin for scale
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Credit: Singapore-MIT Alliance for Research and Technology (SMART)

  • The novel label-free assay uses unconventional L and inverse-L shaped pillars of deterministic lateral displacement (DLD) microfluidic technology to quantify and profile immune states of white blood cells (WBCs) by assessing biophysical properties of size, deformation, distribution, and cell count
  • The assay requires only 20 microlitres (μl) of unprocessed blood and takes just 15 minutes – much faster than existing methods which require up to 15 millilitres (ml) of blood and take at least a few hours to produce results
  • This new technology measures and profiles the often volatile host immune response, resulting in a more accurate assessment of patient pathophysiology
  • Current methods for early diagnosis of infection focus on detecting low-abundance pathogens, and are time-consuming, of low sensitivity, and do not accurately reflect the severity of infection

Singapore, 25 March 2021 – Researchers from Critical Analytics for Manufacturing Personalized-Medicine (CAMP), an Interdisciplinary Research Group (IRG) at the Singapore-MIT Alliance for Research and Technology (SMART), MIT’s research enterprise in Singapore, have developed a new label-free immune profiling assay that profiles the rapidly changing host immune response in case of infection, in a departure from existing methods that focus on detecting the pathogens themselves, which can often be at low levels within a host. This novel technology presents a host of advantages over current methods, being both much faster, more sensitive and accurate.

The new assay is described in a paper titled, “Label-free biophysical markers from whole blood microfluidic immune profiling reveals severe immune response signatures”, published recently in Small, a weekly peer-reviewed scientific journal covering nanotechnology, and included a pilot study of 85 donors recruited from the National University Hospital (NUH) emergency department. The paper was led by Dr Kerwin Kwek Zeming, senior postdoctoral associate at SMART CAMP, and co-authored by Professor Jongyoon Han, Principal Investigator at SMART CAMP and Professor of Biological Engineering and Electrical Engineering at MIT, and Dr Win Sen Kuan, Research Director, Emergency Medicine Department, NUH.

In many cases, the main culprit behind disease manifestation, severity of infection, and patient mortality is an overly aggressive host immune response. For instance, the Spanish Flu pandemic of 1918 resulted in a disproportionately high number of deaths among otherwise healthy young adults. This has been attributed to the now well-studied phenomenon of cytokine storms, which precipitate the rapid release of immune cells and inflammatory molecules and are brought on by a hyper-aggressive host immune response. In a more recent example, cases of severe COVID-19 infection often result in death via sepsis and a dysregulated immune response, while current risk stratification methods based on age and comorbidity remain a significant challenge and can be inaccurate. Moreover, current Covid-19 testing does not prognose the severity of the immune response and can thus lead to inefficient deployment of resources in healthcare settings.

In cases of acute infection, the status of a patient’s immune response can often be volatile and may change within minutes. Hence, there exists a pressing need for assays that are able to rapidly and accurately inform on the state of the immune system. This is particularly vital in early triage among patients with acute infection and prediction of subsequent deterioration of disease. In turn, this will better empower medical personnel to make more accurate initial assessments and deliver the appropriate medical response. This can ensure timely intervention in the emergency department (ED) and prevent admission to the intensive care unit (ICU).

The new assay developed by SMART researchers focuses on profiling the rapidly changing host inflammatory response, which in a hyper-aggressive state, can lead to sepsis and death. A 15-minute label-free immune profiling assay from 20 μL of unprocessed blood using unconventional L and inverse-L shaped pillars of DLD microfluidic technology was developed, functioning as a sensitive and quantitative assay of immune cell biophysical signatures in relation to real-time activation levels of WBCs. As WBCs are activated by various internal or external triggers, the assay can sensitively measure both the extent and direction of these changes, which in turn reflect a patient’s current immune response state. As such, the new assay developed by SMART researchers is able to accurately and quickly assess patients’ immune response states by profiling immune cell size, deformability, distribution, and cell counts.

Significantly, the new assay provides considerable advantages over existing methods of profiling the immune system and its activity. These include measuring leukocyte gene expression, cell-surface biochemical markers, and blood serum cytokine profile. Notably, these current methods require sample dilution or pre-processing steps, as well as labour-intensive, expensive equipment and antibody labelling procedures. As a result, these methods generally require a few hours, at minimum, to return results. This is a key pain point and drawback in triage and the emergency department, where clinicians need to make accurate clinical assessments as early as possible. The labour- and time-intensive nature of these current methods significantly limits their clinical utility for rapid triage and prevents their wider implementation within the ER or ICU.

In contrast, as this new SMART assay takes only 15 minutes, uses only 20 μL of whole blood, and only requires video capture frame rates of up to 150 fps, there is considerable potential for the technology to be developed into a portable unit that can perform point-of-care blood-sparing assays which could significantly improve the diagnosis and differentiation of patients in the ER and other primary or critical care settings. This application will enable clinicians to be able to quickly identify at-risk patients and take immediate action to mitigate or prevent organ dysfunction and other adverse effects of a hyper-aggressive immune response.

Lead author Dr Kerwin Kwek said, “Our new DLD assay will help address an unmet need in the ER and ICU by significantly reducing waiting time for accurate patient assay results. This could lead to more effective triage decision-making and more appropriate and timely treatment, which are critical to saving lives. More generally, this groundbreaking technology provides new insights into both the engineering of precision microfluidics and clinical research.”

Professor Jongyoon Han added, “In the wake of lessons learnt in emergency rooms in hospitals across the world especially during the COVID-19 pandemic, where medical professionals have been faced with making difficult and at times life-or-death decisions in triage, this new technology represents a hugely exciting and significant breakthrough. By reducing the time taken for assay results from hours to a matter of minutes, SMART CAMP’s new assay could help save lives as we continue to combat the scourge of pathogens and infectious diseases. The assay will also have wider applications, giving clinicians a new and more effective tool in the ER and ICU.”

###

The research is carried out by SMART and supported by the National Research Foundation (NRF) Singapore under its Campus for Research Excellence And Technological Enterprise (CREATE) programme.

About Critical Analytics for Manufacturing Personalized-Medicine (CAMP)

CAMP is a SMART interdisciplinary research group launched in June 2019. It focuses on better ways to produce living cells as medicine, or cellular therapies, to provide more patients access to promising and approved therapies. The investigators at CAMP address two key bottlenecks facing the production of a range of potential cell therapies: critical quality attributes (CQA) and process analytic technologies (PAT). Leveraging deep collaborations within Singapore and MIT in the United States, CAMP invents and demonstrates CQA/PAT capabilities from stem to immune cells. Its work addresses ailments ranging from cancer to tissue degeneration, targeting adherent and suspended cells, with and without genetic engineering.

CAMP is the R&D core of a comprehensive national effort on cell therapy manufacturing in Singapore.

For more information, please visit: https://camp.smart.mit.edu/

About Singapore-MIT Alliance for Research and Technology (SMART)

Singapore-MIT Alliance for Research and Technology (SMART) is MIT’s Research Enterprise in Singapore, established by the Massachusetts Institute of Technology (MIT) in partnership with the National Research Foundation of Singapore (NRF) since 2007. SMART is the first entity in the Campus for Research Excellence and Technological Enterprise (CREATE) developed by NRF. SMART serves as an intellectual and innovation hub for research interactions between MIT and Singapore. Cutting-edge research projects in areas of interest to both Singapore and MIT are undertaken at SMART. SMART currently comprises an Innovation Centre and five Interdisciplinary Research Groups (IRGs): Antimicrobial Resistance (AMR), Critical Analytics for Manufacturing Personalized-Medicine (CAMP), Disruptive & Sustainable Technologies for Agricultural Precision (DiSTAP), Future Urban Mobility (FM) and Low Energy Electronic Systems (LEES).

SMART research is funded by the National Research Foundation Singapore under the CREATE programme.

For more information, please visit: http://smart.mit.edu/

For media queries, please contact:

Glenn Tan

SMART@bluetotem.co

+65 9658 5749

Prolonged immune response may contribute to post-COVID-19 blood clots

Prolonged immune response may contribute to post-COVID-19 blood clots

  • March 23, 2021

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IMAGE: SARS-CoV-2, the virus that causes COVID-19
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Credit: Public domain

Serious complications due to blood clots, such as heart attacks and strokes, that are experienced by some COVID-19 survivors may be caused by a lingering immune response in the blood vessels after recovery, suggests a study published today in eLife.

The findings may help explain why some COVID-19 survivors, so-called ‘long-haulers’, report lasting COVID-19 symptoms or why some experience strokes or heart attacks weeks or months after recovery. They may also suggest potential strategies to help prevent these complications.

“During the initial stages of infection, SARS-CoV-2, the virus that causes COVID-19, may attack the lining of the blood vessels which can trigger inflammation and an immune response. This can result in blood vessel damage in the short term,” explains first author Florence Chioh, Research Assistant at the Lee Kong Chian School of Medicine (LKCMedicine), Nanyang Technological University, Singapore. “For our study, we wanted to investigate what happens in the blood vessels of COVID-19 survivors over the longer term.”

Chioh and colleagues collected blood samples from COVID-19 survivors within a month of their recovery and discharge from the hospital. They found that, in comparison with healthy individuals, COVID-19 survivors have twice as many damaged blood vessel cells, called circulating endothelial cells, floating in their blood. Even more of these damaged blood vessel cells were found in survivors who had conditions such as hypertension or diabetes that can also damage the blood vessels.

In addition to signs of blood vessel damage, the team found that survivors had an abundance of inflammatory proteins called cytokines that are produced by immune cells. They also found unusually high numbers of immune cells called T cells, which help destroy viruses, despite the fact that the virus was already gone.

“We show that an overactive immune system is the likely cause of blood vessel damage seen in some COVID-19 survivors,” Chioh says. “This may cause ‘leakiness’ in the blood vessels that increases the risk of blood clots.”

“Our work suggests that COVID-19 patients, especially those with underlying chronic conditions, may benefit from close post-recovery monitoring,” adds senior author Christine Cheung, Assistant Professor and Provost’s Chair in Medicine at LKCMedicine. “This would help identify high-risk individuals who may need blood thinners or preventative therapy to protect them from debilitating blood-clotting complications.”

###

Media contact

Emily Packer,
Media Relations Manager

eLife

e.packer@elifesciences.org

+44 (0)1223 855373

About eLife

eLife is a non-profit organisation created by funders and led by researchers. Our mission is to accelerate discovery by operating a platform for research communication that encourages and recognises the most responsible behaviours. We aim to publish work of the highest standards and importance in all areas of biology and medicine, including Cell Biology, and Immunology and Inflammation, while exploring creative new ways to improve how research is assessed and published. eLife receives financial support and strategic guidance from the Howard Hughes Medical Institute, the Knut and Alice Wallenberg Foundation, the Max Planck Society and Wellcome. Learn more at https://elifesciences.org/about.

To read the latest Cell Biology research published in eLife, visit https://elifesciences.org/subjects/cell-biology.

And for the latest in Immunology and Inflammation, see https://elifesciences.org/subjects/immunology-inflammation.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

New therapy extends breast cancer survival rate, prevents reoccurrence

Common inflammatory bowel disease treatment linked to reduced COVID-19 antibody response

  • March 22, 2021

New evidence indicates the commonly-prescribed inflammatory bowel disease (IBD) drug infliximab blunts the immune system to COVID-19 infection, potentially increasing the risk of reinfection.

The findings arose from the CLARITY study, which recruited 6,935 patients with Crohn’s disease and ulcerative colitis from 92 UK hospitals between September and December 2020. It found that fewer than half of people with IBD who were treated with infliximab had detectable antibodies after SARS-CoV-2 infection, the coronavirus that causes COVID-19.

The study is led by gastroenterologists at the Royal Devon and Exeter NHS Foundation Trust and the University of Exeter Medical School and supported by Crohn’s and Colitis UK and the UK National Institute for Health Research (NIHR).

The authors say an impaired immune response may boost susceptibility to recurrent COVID-19 and help drive the evolution of new variants of SARS-CoV-2, the virus responsible for the infection, warn the researchers. However, they are encouraging people to continue to take their medication as overall Covid-19 risk remains very low.

Careful monitoring of patients with IBD treated with infliximab, who have been vaccinated against COVD-19, will be needed to ensure they mount a strong enough antibody response to ward off the infection, they advise.
CLARITY study lead, Professor Tariq Ahmad, of the University of Exeter Medical School, said: “The poor antibody responses observed in patients treated with infliximab raise the possibility that some patients may not develop protective immunity after COVID-19 infection, and might be at increased risk of reinfection. What we don’t yet know is how use of anti-TNF drugs will impact antibody responses to vaccination.”

The study underlines the importance of fast-paced research to address important questions in people affected by IBD. Professor Ahmad said: “The CLARITY IBD study will continue to follow participants for 40 weeks to investigate important questions regarding the impact of immunosuppressive drugs on immunity to SARS-CoV-2 infection and COVID-19. Modified vaccine schedules may be required if impaired antibody responses are also observed following vaccination. However, because the overall risk of COVID-19 is low in this patient group, we would still strongly encourage patients to continue to take anti-TNF medicines.”

Around two million people worldwide are prescribed anti-tumour necrosis factor (anti-TNF)drugs, which include infliximab. Anti-TNF drugs are effective treatments for immune-mediated inflammatory diseases, but by suppressing the immune system, they can reduce vaccine effectiveness and increase risk of serious infection. The CLARITY study, published in GUT, sought to investigate the impact of infliximab on immune responses to SARS-CoV-2 in patients with IBD.

500,000 people across the UK live with Inflammatory bowel disease (IBD) of which ulcerative colitis and Crohn’s disease, are the two main forms. Symptoms include urgent and frequent bloody diarrhoea, weight loss, pain, and extreme fatigue. At the start of the COVID-19 pandemic the UK Government advised that patients taking anti-TNF medicines could be at increased risk of complications from coronavirus. All were advised to follow strict social distancing measures, and some, depending on the severity of their condition, were advised to shield.

In the CLARITY study researchers compared antibody responses to SARS-CoV-2 in patients treated with infliximab to an alternative medication, vedolizumab that blocks inflammatory cells entering the gut without reducing immune responses to infections or vaccinations.
Rates of COVID-19 infection and hospitalisations were similar between infliximab- and vedolizumab-treated patients. However, infliximab-treated patients were much less likely to subsequently have a positive antibody test. These findings could not, therefore, be explained by differences in acquisition or severity of infection alone. Rather, infliximab seemed to be directly influencing antibody responses to infection. In keeping with this idea, rates of positive antibody tests were lowest in participants who were also taking other drugs that suppress the immune system, such as azathioprine, mercaptopurine or methotrexate.

Dr Nick Powell, of Imperial College London, said the CLARITY team is now exploring the role of other elements of the immune system, which may still protect against reinfection. “Although we clearly observed diminished antibody responses in patients taking infliximab, we haven’t yet completed our investigation of T-cell and other protective immune responses against the virus. I would expect that even in the presence of less efficient antibody production, infliximab-treated patients will mobilise some protective aspect of their immune system to defend themselves.”

Professor Danny Altmann, Professor of Immunology, at Imperial College London, said: “Many people with IBD who are taking infliximab have been shielding throughout this pandemic, so little is known about their susceptibility to COVID-19. They’re not eligible for phase 3 trials so there’s also a knowledge gap around their vaccine response. At this stage it’s really key to start to collect the ‘real life’ data about their immunity and susceptibility. This study starts to offer some answers, including how best to understand and monitor how these individuals progress coming out of shielding and how well they respond to vaccination.”

Sarah Sleet, Chief Executive Officer at Crohn’s & Colitis UK, said: “The CLARITY results are an important first step in helping us understand how different medicines for Crohn’s and Colitis affect a person’s response to coronavirus. At this stage the key message is people with Crohn’s and Colitis should keep taking their medication to stay well and take the vaccine when offered. But we also need research like this to continue. A huge number of people with Crohn’s and Colitis have had to contend with the stresses of shielding and social distancing, and it’s vital this group is prioritised in research.”

###

The paper is entitled “Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab”, published in GUT.

If you would like further information regarding this study please contact rde-tr.clarityibd@nhs.net or visit @CLARITYIBD for more updates.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Weizmann Scientists Find That Bacteria May Aid Anti-Cancer Immune Response

Weizmann Scientists Find That Bacteria May Aid Anti-Cancer Immune Response

  • March 22, 2021

Newswise — Cancer immunotherapy may get a boost from an unexpected direction: bacteria residing within tumor cells. In a new study published in Nature, researchers at the Weizmann Institute of Science and their collaborators have discovered that the immune system “sees” these bacteria and shown that they can be harnessed to provoke an immune reaction against the tumor. The study may also help clarify the connection between immunotherapy and the gut microbiome, explaining the findings of previous research showing that the microbiome affects the success of immunotherapy.

Immunotherapy treatments of the past decade or so have dramatically improved patients’ recovery rates from certain cancers, particularly malignant melanoma; even so, they only work in about 40% of melanoma cases. Prof. Yardena Samuels of Weizmann’s Department of Molecular Cell Biology studies molecular “signposts” – protein fragments, or peptides, on the cell surface – that mark cancer cells as foreign and may therefore serve as potential targets for immunotherapy. In the new study, she and her colleagues extended their search for novel cancer signposts leading to those bacteria known to colonize tumors.

Using methods developed by her departmental colleague Dr. Ravid Straussman, who was one of the first to reveal the nature of the bacterial “guests” in cancer cells, Prof. Samuels and her team, led by Dr. Shelly Kalaora and Adi Nagler (joint co-first authors), analyzed tissue samples from 17 metastatic melanoma tumors derived from nine patients. After obtaining bacterial genomic profiles of these tumors, they then applied an approach known as HLA peptidomics to identify tumor peptides that can be recognized by the immune system. 

The research was conducted in collaboration with Dr. Jennifer A. Wargo of the University of Texas MD Anderson Cancer Center, Houston; Prof. Scott N. Peterson of Sanford Burnham Prebys Medical Discovery Institute, La Jolla; Prof. Eytan Ruppin of the National Cancer Institute, Baltimore; Prof. Arie Admon of the Technion – Israel Institute of Technology; and other scientists.

The HLA peptidomics analysis revealed nearly 300 peptides from 41 different bacteria on the surface of the melanoma cells. The crucial new finding was that the peptides were displayed on the cancer cell surfaces by HLA protein complexes, which are present on the membranes of every cell in our bodies and play a role in regulating the immune response. One of the HLA’s jobs is to sound an alarm about anything foreign by “presenting” foreign peptides to the immune system so that immune T-cells can “see” them. “Using HLA peptidomics, we were able to reveal the HLA-presented peptides of the tumor in an unbiased manner,” Dr. Kalaora says. “This method has already enabled us in the past to identify tumor antigens that have shown promising results in clinical trials.”

It is unclear why cancer cells should perform a seemingly suicidal act by presenting bacterial peptides to the immune system, which can respond by destroying the cells. But whatever the reason, the fact that malignant cells do display these peptides in such a manner reveals an entirely new type of interaction between the immune system and the tumor.

This revelation supplies a potential explanation for how the gut microbiome affects immunotherapy. Some of the bacteria the team identified were known gut microbes. The presentation of the bacterial peptides on the surface of tumor cells is likely to play a role in the immune response, and future studies may establish which bacterial peptides enhance that immune response, enabling physicians to predict the success of immunotherapy and to tailor a personalized treatment accordingly.

Moreover, the fact that bacterial peptides on tumor cells are visible to the immune system can be exploited for enhancing immunotherapy. “Many of these peptides were shared by different metastases from the same patient or by tumors from different patients, which suggests that they have a therapeutic potential and a potent ability to produce immune activation,” Nagler says.

In a series of continuing experiments, Prof. Samuels and her colleagues incubated T cells from melanoma patients in a laboratory dish along with bacterial peptides derived from tumor cells from the same patient. The result: T cells were activated specifically toward the bacterial peptides.  

“Our findings suggest that bacterial peptides presented on tumor cells can serve as potential targets for immunotherapy,” Prof. Samuels said. “They may be exploited to help immune T cells recognize the tumor with greater precision, so that these cells can mount a better attack against the cancer. This approach can in the future be used in combination with existing immunotherapy drugs.”

Also participating in this research at the Weizmann Institute were Dr. Deborah Nejman, Dr. Michal Alon, Chaya Barbolin, Dr. Ronen Levy, Sophie Trabish, Dr. Leore Geller, Polina Greenberg, Gal Yagel, Dr. Aviyah Peri, and Lior Roitman from the Department of Molecular Cell Biology; Yuval Bussi, Dr. Adina Weinberger, Maya Lotan-Pompan, and Prof. Eran Segal from the Department of Computer Science and Applied Mathematics and the Department of Molecular Cell Biology; Dr. Ron Rotkopf and Ofra Golani from the Life Sciences Core Facilities Department; Dr. Tali Dadosh and Dr. Smadar Levin-Zaidman from Chemical Research Support Department; Dr. Garold Fuks from the Department of Physics of Complex Systems; and Dr. Raya Eilam from the Veterinary Resources Department.

Prof. Yardena Samuels’s research is supported by the EKARD Institute for Cancer Diagnosis Research; the Weizmann-Brazil Tumor Bank; the Moross Integrated Cancer Center; the Laboratory in the Name of M.E.H. Fund established by Margot and Ernst Hamburger; the Green Family Charitable Foundation; the Wagner-Braunsberg Family Melanoma Research Fund; the Jean-Jacques Brunschwig Fund for the Molecular Genetics of Cancer; the Erica Drake Fund; Miel de Botton; the Rising Tide Foundation; the Fundación Ramón Areces; the Hanna and Dr. Ludwik Wallach Cancer Research Fund; the Jacques Asseoff Trust; the estate of Adrian Finer; the estate of Mady Dukler; Karl-Johan Persson; and the estate of Malka Moskowitz. Prof. Samuels is the incumbent of the Knell Family Professorial Chair.

The Weizmann Institute of Science in Rehovot, Israel, is one of the world’s top-ranking multidisciplinary research institutions. The Institute’s 3,800-strong scientific community engages in research addressing crucial problems in medicine and health, energy, technology, agriculture, and the environment. Outstanding young scientists from around the world pursue advanced degrees at the Weizmann Institute’s Feinberg Graduate School. The discoveries and theories of Weizmann Institute scientists have had a major impact on the wider scientific community, as well as on the quality of life of millions of people worldwide.

Study examines how sleep, stress, age, and obesity could impact the immune response to COVID vaccine

UCSF researchers looking at how sleep, stress, age, and obesity could impact the immune response to COVID vaccine

  • March 18, 2021
SAN FRANCISCO (KGO) — It’s possible the amount of sleep you’re getting and the stress you’re under could impact your COVID vaccine, meaning the strength and durability of the vaccine may have more to do with you, your body, and your lifestyle than you expected.

UCSF professor of psychiatry, Elissa Epel, and a team of researchers are recruiting for a study to examine how stress, age, and sleep, affect the immune response with the COVID vaccine.

“What we know from the flu vaccine is that stress, particularly bereavement stress, caregiving stress, really major chronic stress, dampens the immune response,” said Epel, who is working to find out if that holds true for the COVID vaccines.

The Path Forward: Lessons learned, journey ahead 1 year into the COVID-19 pandemic

Age is really not just a number. Epel said that through bloodwork they will be looking for different signs of aging, as it affects the immune response. “When people walk in, of course, their chronological age, because we know that predicts immune response. But we’re also measuring the biological age of their immune system, and then these lifestyle factors that we think are so important because we can control these.”

As for sleep… “we think that getting seven hours of sleep a night is critical, but especially right around the vaccination period. We also think that our daily mood is going to be important with the COVID vaccination, it’s been shown to be important with the flu vaccination,” explained Epel, “so when people join our study, they actually take a close look at the different stressful situations in their life.”

BOOST study participants will undergo three blood draws over seven months. The first draw is done before the COVID vaccine to determine the baseline antibody level. The second and third draws will measure peak antibody response and length of protection.

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“We need to learn how to optimize our own immune response. We also think these findings will have implications for boosters,” said Epel. “This will help us identify subgroups who may need boosters.”

Another factor that could influence immune response is obesity.

“It’s been known for decades that people who are obese, have a defective level of antibody production in response to vaccines,” said Dr. Robert Lustig, a pediatric endocrinologist at UCSF. Obesity is not part of the BOOST study, but it is on the radar of doctors and scientists looking into COVID immunity.

Kate Larsen: “Down the line if, you have obesity or another high-risk health condition might you get a booster sooner than someone who doesn’t have one of those conditions?

Dr. Robert Lustig: “We don’t know the answer to that. We’ll see what happens with COVID. It may be that we’re all going to be getting new shots because of these new variants.”

The BOOST study is looking for a diverse group of participants, particularly people over 60 who have not yet been vaccinated. Participants will get paid.

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Copyright © 2021 KGO-TV. All Rights Reserved.

Study examines how sleep, stress, age, and obesity could impact the immune response to COVID vaccine

Study examines how sleep, stress, age, and obesity could impact the immune response to COVID vaccine

  • March 17, 2021
SAN FRANCISCO — It’s possible the amount of sleep you’re getting and the stress you’re under could impact your COVID vaccine, meaning the strength and durability of the vaccine may have more to do with you, your body, and your lifestyle than you expected.

UCSF professor of psychiatry, Elissa Epel, and a team of researchers are recruiting for a study to examine how stress, age, and sleep, affect the immune response with the COVID vaccine.

“What we know from the flu vaccine is that stress, particularly bereavement stress, caregiving stress, really major chronic stress, dampens the immune response,” said Epel, who is working to find out if that holds true for the COVID vaccines.

Age is really not just a number. Epel said that through bloodwork they will be looking for different signs of aging, as it affects the immune response. “When people walk in, of course, their chronological age, because we know that predicts immune response. But we’re also measuring the biological age of their immune system, and then these lifestyle factors that we think are so important because we can control these.”

As for sleep… “we think that getting seven hours of sleep a night is critical, but especially right around the vaccination period. We also think that our daily mood is going to be important with the COVID vaccination, it’s been shown to be important with the flu vaccination,” explained Epel, “so when people join our study, they actually take a close look at the different stressful situations in their life.”

BOOST study participants will undergo three blood draws over seven months. The first draw is done before the COVID vaccine to determine the baseline antibody level. The second and third draws will measure peak antibody response and length of protection.

“We need to learn how to optimize our own immune response. We also think these findings will have implications for boosters,” said Epel. “This will help us identify subgroups who may need boosters.”

Another factor that could influence immune response is obesity.

“It’s been known for decades that people who are obese, have a defective level of antibody production in response to vaccines,” said Dr. Robert Lustig, a pediatric endocrinologist at UCSF. Obesity is not part of the BOOST study, but it is on the radar of doctors and scientists looking into COVID immunity.

Kate Larsen: “Down the line if, you have obesity or another high-risk health condition might you get a booster sooner than someone who doesn’t have one of those conditions?

Dr. Robert Lustig: “We don’t know the answer to that. We’ll see what happens with COVID. It may be that we’re all going to be getting new shots because of these new variants.”

The BOOST study is looking for a diverse group of participants, particularly people over 60 who have not yet been vaccinated. Participants will get paid.

Copyright © 2021 KGO-TV. All Rights Reserved.

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How pregnancy turns the stress response on its head

  • March 16, 2021

COLUMBUS, Ohio – The link between psychological stress and physical health problems generally relates to a stress-induced immune response gone wild, with inflammation then causing damage to other systems in the body. It’s a predictable cascade – except in pregnancy, research suggests.

Scientists exploring the negative effects of prenatal stress on offspring mental health set out to find the immune cells and microbes in stressed pregnant mice most likely to trigger inflammation in the fetal brain – the source for anxiety and other psychological problems identified in previous research.

Instead, the researchers found two simultaneous conditions in response to stress that made them realize just how complex the cross-talk between mom and baby is during gestation: Immune cells in the placenta and uterus were not activated, but significant inflammation was detected in the fetal brain.

They also found that prenatal stress in the mice led to reductions in gut microbial strains and functions, especially those linked to inflammation.

“I thought it was going to be a fairly straightforward tale of maternal inflammation, changes in microbes and fetal inflammation. And while the changes in microbes are there, the inflammation part is more complex than I had anticipated,” said Tamar Gur, senior author of the study and assistant professor of psychiatry and behavioral health, neuroscience, and obstetrics and gynecology at The Ohio State University.

“The complex interplay between the stress response and the immune system is dysregulated by stress, which is problematic for the developing fetus. There are key changes during this critical window that can help shape the developing brain, so we want to figure out how we could potentially intervene to help regulate these systems.”

The study was published recently in Scientific Reports.

Most attention paid to the negative effects of prenatal stress on offspring mental health focus on disruptive major life events or exposure to disaster, but evidence also suggests that up to 84% of pregnant women experience some sort of stress.

In a previous study, Gur’s lab found that prenatal stress’s contributions to life-long anxiety and cognitive problems in mouse offspring could be traced to changes in microbial communities in both mom and baby.

Gur focuses on the intrauterine environment in her search for factors that increase the risk for prenatal stress’s damaging effects, and this newer study opened her eyes to how complicated that environment is.

“The dogma would be that we’re going to see an influx of immune cells to the placenta. The fact that it’s suppressed speaks to the powerful anti-inflammatory response of the mom. And that makes sense – a fetus is basically a foreign object, so in order to maintain pregnancy we need to have some level of immunosuppression,” said Gur, also an investigator in Ohio State’s Institute for Behavioral Medicine Research and a maternal-fetal psychiatrist at Ohio State Wexner Medical Center.

“We want to figure out what is at the interface between mom and baby that is mediating the immunosuppressive effect on the maternal side and the inflammation on the fetal side. If we can get at that, we’ll get really important keys to understanding how best to prevent the negative impact of prenatal stress.”

Prevention could come in the form of prebiotics or probiotics designed to boost the presence of beneficial microbes in the GI tract of pregnant women. Maternal microbes affect the brains and immune systems of developing offspring by producing a variety of chemicals the body uses to manage physiological processes.

“I think microbes hold really important clues and keys, making them a tantalizing target for intervention. We can do things about individuals’ microbes to benefit both mom and baby,” Gur said.

To mimic prenatal stress during the second and early third trimesters, pregnant mice in her lab are subjected to two hours of restraint for seven days to induce stress. Control mice are left undisturbed during gestation.

In this recent study, the researchers found stress in mice activated steroid hormones throughout the body – the sign of a suppressed immune system – and resulted in lower-than-expected populations of immune cells in reproductive tissue, suggesting that the uterus was effectively resisting the effects of the stress.

An examination of colon contents showed differences in microbial communities between stressed and non-stressed mice, with one family of microbes that influences immune function markedly decreased in stressed mice. The researchers found that stress showed few signs of gene-level changes in the colon that could let bacteria escape to the bloodstream – one way that microbes interfere with body processes.

“There are absolutely changes in microbes that might help explain key pathways that are important for health and the immune system, especially when it comes to the placenta and the mom’s immune system,” Gur said.

In future studies, her lab will examine immune cells in the fetal brain and monitor how gene expression changes in cells in the placenta in response to stress. She is also leading an ongoing observational study in women, tracking microbes, inflammation and stress levels during and after pregnancy.

###

This work was supported by grants from the National Institutes of Health and startup funds from Ohio State. Co-authors, all from Ohio State, include Adrienne Antonson, Morgan Evans, Jeffrey Galley, Helen Chen, Therese Rajasekera, Sydney Lammers, Vanessa Hale and Michael Bailey.

Contact:
Tamar Gur,
tamar.gur@osumc.edu

Written by Emily Caldwell,
Caldwell.151@osu.edu

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