Category Archives: Immunology

Immunology

Coronavirus antibodies last at least three months after infection, U of T study finds – News@UofT

Coronavirus antibodies can last at least three months after a person becomes infected with the virus that causes COVID-19, according to a study published in Science Immunology.

Researchers from the University of Toronto and the Lunenfeld-Tanenbaum Research Instituteat Sinai Health used both saliva and blood samples from COVID-19 patients to measure and compare antibody levels for over three months post-symptom onset.

They found that antibodies of the IgG class that bind to the SARS-CoV-2 spike protein are detectable for at least 115 days, representing the longest time interval measured. The study is also the first to show these antibodies can also be detected in the saliva.

Our study shows that IgG antibodies against the spike protein of the virus are relatively durable in both blood and saliva, said Jennifer Gommerman, professor of immunology in U of Ts Temerty Faculty of Medicine and leader of the saliva testing effort.

Our study suggests saliva may serve as an alternative for antibody testing. While saliva is not as sensitive as serum, it is easy to collect.

The saliva assay was developed at U of Twhile a team at Lunenfeld-Tanenbaum, led by senior investigator Anne-Claude Gingras, who is also a professor of molecular genetics at U of T, executed the serum assay.

The LTRI platform for detection of antibodies in serum, or blood, is incredibly robust and well suited for assessing the prevalence of infection within the community, said Gingras. This is another tool that can help us better understand and even overcome this virus.

Anne-Claude Gingras, a professor of molecular genetics at U of T, led a team at theLunenfeld-Tanenbaum Research Institute that executed the serum assay for the study (photo courtesy of Mount Sinai Hospital)

Most people who recover from COVID-19 develop immune agents in their blood called antibodies that are specific to the virus. These antibodies are useful in indicating who has been infected, regardless of whether they had symptoms or not.

A large team of scientists collaborated on the study, including Allison McGeer and Mario Ostrowski, who provided access to the paired saliva and serum samples from dozens of patients for the study.

McGeer is a professor of laboratory medicine and pathobiology at U of T, a senior clinician scientistat Lunenfeld-Tanenbaum and principal investigator of the Toronto Invasive Bacterial Diseases Network. Ostrowski is a professor of medicine, immunology, and laboratory medicine and pathobiology at U of Tand a scientist at St. Michaels Hospital, Unity Health Toronto.

The study was co-led by U of T graduate students Baweleta Isho, Kento Abe, Michelle Zuo and Alainna Jamal. James Rini, a professor of biochemistry and molecular genetics at U of T, and Yves Durocher from the National Research Council of Canada, provided key protein reagents for the saliva studies.

The durability of the antibody response to SARS-CoV-2 has been debated in recent months. An earlier study published in Nature Medicine suggested the antibodies can disappear after two months for some individuals who had the virus but did not experience symptoms.

This study led by the Toronto team is in agreement with findings from leading immunologists in the U.S. in describing the antibody response as longer lasting.

While the team admits there is a lot they still dont know about antibody responses to SARS-CoV-2 infection, including how long the antibodies last beyond this period or what protection they afford against re-infection, the research could have broader implications in the development of an effective vaccine.

This study suggests that if a vaccine is properly designed, it has the potential to induce a durable antibody response that can help protect the vaccinated person against the virus that causes COVID-19, Gommerman said.

The researchwas supported by an Ontario Together grant and funding from the Canadian Institutes of Health Research. Funding for the development of the assays in the Gingras lab was provided through donations bythe Royal Bank of Canada, Questcap and the Krembil Foundation.

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Coronavirus antibodies last at least three months after infection, U of T study finds - News@UofT

Immunology

Kirby Institute awarded over $7m for HIV, hepatitis C and COVID-19 immunology research – UNSW Newsroom

A combined $7.55 million has been awarded to two immunology projects at the Kirby Institute at UNSW Sydney via the Australian governments Medical Research Future Fund (MRFF) scheme.

Through the Pathogen Genomics initiative, $6.6 million has been awarded to a large collaborative, multidisciplinary team led by Kirby Institute Director Professor Anthony Kelleher, to investigate the effectiveness of HIV and hepatitis C public health initiatives using viral genomics.

The significant project will see the establishment of national networks, governance and infrastructure to enable enhanced collection of public health metadata and viral sequence for HIV and hepatitis C across the country.

Using the latest technology and innovation in molecular epidemiology, this research will facilitate the rapid genomic analysis of virus diversity and transmissions networks for HIV and hepatitis C infection in Australia, in near real-time, says Prof. Kelleher.

Very importantly, these systems will be developed in partnership with peak community bodies to ensure patient privacy is a primary consideration, and that any systems developed are acceptable to affected communities.

The project, which is the first of its kind in Australia, will deploy high-level viral sequencing and bioinformatic systems into existing clinical and public health networks. This will enable the identification of trends in virus spread and new infections and enhance the already highly effective public health response to these increasingly dispersed epidemics.

The ability to conduct molecular epidemiological analyses in near real-time will improve Australias already world-class response to HIV and hepatitis C, by allowing us to finely map the effectiveness of particular public health strategies, and to optimise our efforts by identifying areas where more targeted campaigns are necessary. We hope this model will allow more effective use of public health investments and allow targeting to areas of greatest need, says Prof. Kelleher.

This ambitious research program will be conducted in close collaboration with colleagues within the Public Health Laboratory Network (PHLN), jurisdictional public health units, industry and multiple partners from community.

The current COVID-19 pandemic has shown the importance and effectiveness of a coordinated nation-wide system for the collection, analysis and interpretation of pathogen transmission. We hope this project will fill the gaps of current prevention strategies, enabling a rapid and effective public health response with the aim of virtually eliminating these infections in Australia," says Prof. Kelleher.

A grant of $995,500 has been awarded to a team from the Kirby Institute, UNSW, Lifeblood, the Garvan Institute and St Vincents Centre for Applied clinical research. Led by Associate Professor Stuart Turville, the research will explore the bodys immune response to COVID-19.

People who become infected with SARS-CoV-2 have a range of immune responses. Some clear the virus with limited involvement of antibodies and other forms of longer term acquired immunity, says A/Prof. Turville.

Other patients mount a longer, sustained response, with secretion of high levels of antibodies and mobilisation of T cells, a key component of cellular immunity. The latter are produced to combat the spread of the virus in patients that may have symptoms of greater disease severity.

This project will analyse patient antibodies and cells over time. Many assays have already been developed from scratch in the Kirby Institutes Glendonbrook Laboratories to map the COVID-19 immune response.

A/Prof. Turville says it is critical to understand the immune response in great detail, in order to inform public health measures, treatment and vaccine delivery.

By studying the immune response in a range of patients, we will be able to understand the overall risk of re-infection in the community and if the immune response contributes to any ongoing symptoms following COVID-19 infection, he says.

The research will identify patients with potent immune responses to the virus, and will investigate how and why certain individuals have mounted a greater immune response. This information will be used to understand natural immunity to the virus and for immunotherapy and vaccine development.

A key aspect of the study will combine highly sensitive and novel methodology to follow two unique patient cohorts. The first is through a collaborative partnership with Australian Red Cross Lifeblood, which coordinates thousands of blood donors nationwide who have recovered from COVID-19. The second is a Sydney-based cohort called ADAPT, headed by the Kirby Institutes Associate Professor Gail Mathews at St Vincents Hospital. Combining both cohorts, the study will not only give us a snapshot of the overall immune responses across Australia, but also how this relates to disease severity and ongoing COVID-19-related symptoms.

The need for knowledge of the immune response, along with the right biomedical tools, is paramount in building the arsenal to stop the spread of COVID-19, and in the short term, generating immunotherapeutics to save peoples lives, says A/Prof. Turville.

Professor Tony Butler, from the School of Population Health at UNSW Medicine, was awarded $232,159 to investigate the mental health needs of the Australian population during COVID-19. Prof. Butlers project will use an automated method, including text mining and data linkage, to process police records over the past four years and investigate whether there have been any increases in mental illnesses both before and during the COVID-19 crisis.

Pro Vice-Chancellor Research Professor Ana Deletic congratulates all of the grant recipients.

These three grants are a testament to the fact that UNSWs high performing research in virology is among the best in Australia and we remain focused on delivering impactful outcomes in medical research, Prof. Deletic says.

It is pleasing that in 2020 we have been awarded over $90 million in MRFF grants which is becoming one of our largest funding sources.

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Kirby Institute awarded over $7m for HIV, hepatitis C and COVID-19 immunology research - UNSW Newsroom

Immunology

HKUMed develops a novel therapeutic approach against Epstein-Barr virus-associated tumours by using exosomes derived from V2-T cells – India Education…

A research team at LKS Faculty of Medicine, The University of Hong Kong (HKUMed) discovered that exosomes derived from V2-T cells (V2-T-Exos) can effectively control Epstein-Barr virus-associated tumours and induce T-cell anti-tumour immunity. The novel findings of V2-T-Exos provide insights into new therapeutic approach for Epstein-Barr virus (EBV)-associated tumours. The ground-breaking findings have been published in the leading academic journal, Science Translational Medicine. [Link to the publication]

BackgroundEBV infects about 95% of the human population and causes more than 200,000 cases of cancer each year and that around 2% of all cancer deaths are due to EBV-attributable malignancies. EBV-associated tumours include Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, gastric tumour and post-transplant lymphoproliferative disease, etc. Current treatment options for EBV-associated tumours are limited with considerably unwanted off-target toxicities and incomplete effectiveness for relapsed or refractory disease. V2-T cells are innate-like T cells with anti-tumour potentials against EBV-associated tumours. Unfortunately, its clinical translation is limited because V2-T cells from some cancer patients are difficult to be expanded. Exosomes are endosome-originated small extracellular vesicles that mediate intercellular communication. Compared with cell-based therapy, cell-free exosomes have advantages with higher safety, easier storage, and lower costs. However, the anti-tumour activity of exosomes derived from V2-T cells (V2-T-Exos) remains unknown.

Research findingsHerein, the team found that V2-T-Exos contained death-inducing ligands (FasL and TRAIL) and immunostimulatory molecules (CD80, CD86, MHC class I and II). V2-T-Exos targeted and efficiently killed EBV-associated tumour cells through FasL and TRAIL pathways and promoted EBV antigen-specific CD4 and CD8 T cell expansion. Administration of V2-T-Exos effectively controlled EBV-associated tumours in immunodeficient and humanized mice. Because expanding V2-T cells and preparing autologous V2-T-Exos from cancer patients ex vivo in large scale is challenging, the team further explored the anti-tumour activity of allogeneic V2-T-Exos in humanized mouse cancer models. Interestingly, the team found that allogeneic V2-T-Exos had more effective anti-tumour activity than autologous V2-T-Exos in humanized mice; the allogeneic V2-T-Exos increased the infiltration of T cells into tumour tissues and induced more robust CD4 and CD8 T cells-mediated anti-tumour immunity. Compared with exosomes derived from NK cells with direct cytotoxic anti-tumour activity or dendritic cells that induced T-cell anti-tumour responses, V2-T-Exos have dual anti-tumour activities by directly killing tumour cells and indirectly inducing T cells-mediated anti-tumour responses, thus resulting in more effective control of EBV-associated tumours.

Our study provides the first evidence about the anti-tumour activities of V2-T-Exos against EBV-associated tumours. These exosomes could effectively control EBV-associated cancers in multiple mouse models. More importantly, allogeneic V2-T-Exos had higher therapeutic efficacy than autologous V2-T-Exos to control EBV-associated tumours. Therefore, the V2-T-Exos prepared from healthy donors can be used to treat patients with EBV-associated tumours, which is highly beneficial to the clinical application of this novel approach, said Professor Tu Wen-wei, Antony and Nina Chan professor in Paediatric Immunology, Department of Paediatrics and Adolescent Medicine, HKUMed, who led the research.

Significance of the studyThe findings of the study have significant implications in cancer immunotherapy. Firstly, the identification that V2-T-Exos has potent immunostimulatory property suggests that they could be designed as a cancer vaccine by serving as immune adjuvant and delivering immunogens. Secondly, the V2-T-Exos has advantages over other exosome-based therapies (e.g. NK-Exos and DC-Exos) by displaying dual anti-tumour activities and are easier in preparation. Thirdly, the results that allogeneic V2-T-Exos have higher anti-tumour efficacies than autologous V2-T-Exos can greatly enhance the clinical feasibility of V2-T-Exos, because the preparation of allogeneic exosomes does not require personalized procedures and is easier in quality control, standardization and centralization for clinical application.

About the research teamThe research was led by Professor Tu Wen-wei, Antony and Nina Chan Professor in Paediatric Immunology, Department of Paediatrics and Adolescent Medicine, HKUMed. Dr Wang Xi-wei, post-doctoral fellow of Professor Tus team, is the first author. Other researchers include Dr Zheng Xiang, post-doctoral fellow of Professor Tus team; Dr Liu Yin-ping, Research Officer in Department of Paediatrics and Adolescent Medicine, HKUMed; Ms Huang Chun-yu, PhD student of Professor Tu; Dr Pei Yu-jun, post-doctoral fellow of Professor Tus team; Dr Pamela Lee Pui-wah, Clinical Associate Professor, Department of Paediatrics and Adolescent Medicine and Assistant Dean (Clinical Curriculum), HKUMed; Professor Godfrey Chan Chi-fung, Tsao Yen-Chow Professor in Paediatrics and Adolescent Medicine, Head and Clinical Professor of Paediatrics and Adolescent Medicine, HKUMed; Professor Lau Yu-lung, Doris Zimmern Professor in Community Child Health and Chair Professor of Paediatrics, Department of Paediatrics and Adolescent Medicine, HKUMed; Collaborators include Dr Wang Xia, post-doctoral fellow, Department of Pathology, HKUMed; Dr Helen Zhi, Director of Biostatistics and Clinical Research Methodology Unit, School of Public Health, HKUMed; Dr Wilfred Wong Hing-sang, Senior IT Manager, Department of Paediatrics and Adolescent Medicine, HKUMed. Professor Wei Hai-ming, Institute of Immunology, University of Science and Technology of China, Hefei, Anhui, Mainland China; Professor Irene Ng Oi-lin, Loke Yew Professor in Pathology, Director of State Key Laboratory of Liver Research (HKU), Chair of Pathology, HKUMed.

Collaborating institutions contributing to the research include the Institute of Immunology, University of Science and Technology of China, Hefei, Anhui, Mainland China.

This work was supported in part by General Research Fund (17122519, 17126317, 17115015, 17121214), Theme-based Research Scheme from the Research Grants Council (Project No. T11-705/14N), and The Area of Excellence Scheme (AoE/M-06/08) supported by the University Grants Committee, Government of the Hong Kong Special Administrative Region.

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HKUMed develops a novel therapeutic approach against Epstein-Barr virus-associated tumours by using exosomes derived from V2-T cells - India Education...

Immunology

Karen Oates brings biology, immunology expertise to COVID-19 education project – WPI News

Karen Oates

Karen Oates, professor of biology & biotechnology, will coordinate the development of educational materials for a project aimed at teaching college students and the general public about vaccines.

The one-year project is funded by a $199,425 RAPID grant from the National Science Foundation to Santa Clara University. Oates is co-principal investigator on the project, working with scientists and science communicators to develop short YouTube videos, social media content, and project-based teaching materials.

Some studies have shown that a large percentage of 18- to 29-year-olds have said they would not be vaccinated against COVID-19, if a vaccine were available, Oates said. I feel a responsibility to give college students information about vaccines and vaccination so they can make decisions based on science. I want them to understand their responsibilities to their communities when it comes to vaccination, and I want to give them the tools to make the right decisions.

The project will develop educational modules on understanding science, the science of COVID-19, vaccine science, and COVID-19 science communication. Oates, an expert in biochemistry and immunology, plans to test some of the educational materials at WPI during her C Term class on human biology. All materials developed during the project will be free to users and available in English and Spanish, she said.

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Karen Oates brings biology, immunology expertise to COVID-19 education project - WPI News

Immunology

Plasma Fractionation Market to Exhibit a CAGR of 7.6% and Touch USD 48.55 Billion by 2027; Constant Research and Study of immunoglobulin to Lighten…

Pune, Oct. 08, 2020 (GLOBE NEWSWIRE) -- Global plasma fractionation market size is expected to reach USD 48.55 billion by 2027, exhibiting a CAGR of 7.6% during the forecast period. The growing incidence of immunological disorders is expected to spur demand for the market, states Fortune Business Insights, in a report, titled Plasma Fractionation Market Size, Share & COVID-19 Impact Analysis, By Product (Immunoglobulin, Albumin, Coagulation Factors, Protease Inhibitors, and Others), By Application (Immunology & Neurology, Hematology, Critical Care, Pulmonology, and Others), By End-user (Hospitals & Clinics, Clinical Research Laboratories, and Others), and Regional Forecast, 2020-2027. The market size stood at USD 25.44 billion in 2019.

The report on the market of Plasma Fractionation comprises:

Notable Development:

October 2018: Shire announced the commencement of the plasma fractionation facility in Georgia, U.S.

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High R&D for Alzheimers Therapies to Contribute Growth

The growing adoption of immunoglobulin for the management, treatment, and diagnosis of metabolic diseases is expected to have a tremendous impact on the market. The ongoing R&D investments and study of immunoglobulin to treat Alzheimers and other autoimmune disorders therapies will spur business opportunities for the market.

Immunoglobulin is glycoprotein molecules that are derived by plasma fractionation and act as antibodies. Moreover, the growing utilization of immunoglobulin owing to its superior advantages can further incite the development of the market.

The coronavirus incidence has caused severe damage and financial ruin to industries across the globe. The governments of several countries have instigated lockdown to thwart the spread of this deadly virus. Such plans have caused disturbances in the production and supply chain.

But, with time and resolution, we will be able to combat this stern time and get back to normality. Our well-revised reports will help companies to receive in-depth information about the present scenario of every market so that you can adopt the necessary strategies accordingly.

To get to know more about the short-term and long-term impacts of COVID-19 on this market, please visit: https://www.fortunebusinessinsights.com/industry-reports/plasma-fractionation-market-101614

Favorable Government Regulations to Propel Market in North America

The market size in North America is expected to grow profoundly during the forecast period owing to the increasing research and development in the field of plasma. The well-established healthcare infrastructure. The favorable government regulations and FDA approvals are expected to enable speedy expansion of the market in the forthcoming years.

The growing participation in plasma donations is expected to foster the healthy growth of the market. Europe is predicted to witness high growth during the forecast period due to the growing prevalence of rare diseases in the region. The heavy investments in plasma fractionation systems will create lucrative business opportunities for the market.

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The Report Lists the Main Companies in this Plasma Fractionation Market:

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Global Plasma Fractionation Market Segmentations:

By Product Type

Albumin

Immunoglobulin

o Intravenous Immunoglobulin

o Subcutaneous Immunoglobulin

Coagulation Factors

o Factor IX

o Factor VIII

o Prothrombin Complex Concentrates

o Fibrinogen Concentrates

o Others

Protease Inhibitors

Others

By Application

Immunology & Neurology

Hematology

Critical Care

Pulmonology

Others

By End User

Hospitals & Clinics

Clinical Research Laboratories

Others (Academic Institutes, etc)

By Geography

North America (U.S, Canada)

Europe (U.K., Germany, France, Italy, Spain, Scandinavia, and Rest of Europe)

Asia-Pacific (Japan, China, India, Australia, Southeast Asia and Rest of Asia- Pacific)

Latin America (Brazil, Mexico, and Rest of Latin America)

The Middle East and Africa (South Africa, GCC, and Rest of the Middle East and Africa)

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Plasma Fractionation Market to Exhibit a CAGR of 7.6% and Touch USD 48.55 Billion by 2027; Constant Research and Study of immunoglobulin to Lighten...

Immunology

Every COVID-19 case seems different. These scientists want to know why. – Newswise

Newswise LA JOLLAAs scientists around the world develop life-saving COVID-19 vaccines and therapies, many are still wondering exactly why the disease proves deadly in some people and mild in others.

To solve this puzzle, scientists need an in-depth understanding of how the bodys many types of immune cells respond to SARS-CoV-2, the virus that causes COVID-19.

A new international study led by scientists at La Jolla Institute for Immunology (LJI), The University of Liverpool and the University of Southampton is the first to give a detailed snapshot of how the body's CD4+ T cells respond to the SARS-CoV-2 virus. Among the findings, their work suggests that early in the illness, patients hospitalized with severe cases of COVID-19 develop a novel T cell subset that can potentially kill B cells and reduce antibody production.

The study, published on October 6, 2020, in Cell, provides a crucial foundation for further detailed analysisand shows the power of a cutting-edge technique called single-cell RNA sequencing (RNA-seq).

Zooming in on individual cells

This study employs single-cell RNA-seq to analyze RNA molecules expressed by CD4+ T cells that specifically recognize SARS-CoV-2 says LJI Associate Professor Pandurangan Vijayanand, M.D., Ph.D., who led the study with long-time collaborator Christian H Ottensmeier, M.D., Ph.D., FRCP, professor at the University of Liverpool and adjunct professor at LJI. This lets us show, for the first time, the complete nature of the cells that respond to this virus.

This is the beginning, says Ottensmeier, a physician scientist who co-led the study. We needed to have a reference to look back at for further studies, and this work is novel, timely, detailed, innovativeand open.

Vijayanand and his colleagues at LJI have pioneered the use of single-cell RNA-seq in immunology. RNA-seq gives researchers a new window into the gene expression patterns that can make each person's immune response to a virus different. For the new study, the researchers focused on CD4+ T cells, which play many critical roles in fighting infection.

"CD4+ T cells play a central role in orchestrating the immune response," says study co-first author Benjamin Meckiff, Ph.D., postdoctoral fellow at LJI. "They are a heterogeneous population of immune cells carrying out a wide range of functions, and we have been able to specifically analyze their response to SARS-CoV-2."

Vijayanand and Ottensmeier had planned to use single-cell RNA-seq to analyze CD4+ T cells from patients hospitalized for influenza this year. When the pandemic hit, the researchers applied in early March for approval to use samples from COVID-19 patients as well.

We were collecting appropriate samples very early on in the pandemic, says Vijayanand.

The researchers studied samples from 40 COVID-19 patients in two groups. The hospitalized group included 22 patients (with nine treated in the ICU). The non-hospitalized group had 18 patients who had experienced milder COVID-19 symptoms.

The scientists used single-cell RNA-seq to analyze the types of CD4+ T cells that respond to SARS-COV-2 in these patients. Each type of T cell has a role in fighting viruses: some (the "helper" CD4+ T cells) alert the body to infection and recruit other immune cells, while others (TFH cells) signal B cells to make antibodies. Finally, some (Tregs) do the important job of inhibiting other T cells, keeping the immune system from damaging the body's own tissues.

There are multiple flavors of T cells that respond to this virus, says Vijayanand.

The researchers caution that human studies are only correlative and cannot conclude that certain T cell populations are driving disease severity. They do believe some findings warrant a closer look.

For example, the scientists found that hospitalized patients have higher levels of "cytotoxic" TFH cells, which could potentially make an infection worse. Instead of doing their job and helping B cells make antibodies, the cytotoxic TFH cells seen in this study were very similar to cells that have been seen killing B cells in previous studies. The researchers then examined SARS-CoV-2-specific antibody concentrations in patients. Those with dysfunctional TFH cells also had fewer antibodies.

"The TFH cells in hospitalized patients displayed gene signatures that suggest they are dysfunctional and aren't giving the help to B cells that we would expect," says Meckiff.

A baseline for future investigations

Overall, the study gives the scientific community a starting place to explore CD4+ T cell responses to SARS-CoV-2, and the work establishes a baseline for comparing responses in people over time or with different disease severities. To support these efforts, the researchers made their data immediately available online, just two months after the project began.

We had to be quick, says study co-first author Ciro Ramrez-Sustegui, a bioinformatics specialist at LJI. Having the data available for everyone is essential.

Theres definitely more to explore, adds study co-author Vicente Fajardo, an LJI research technician who spearheaded the bioinformatics analysis alongside Ramrez-Sustegui.

In fact, the data and the research method could be important for more than infectious disease research. Ottensmeier explains that a better understanding of how the body responds to viruses can also guide future research into cancer immunotherapies, which would use the bodys own immune system to target and kill cancer cells.

With this study, we levied our long-standing collaboration for a new human health puzzle, says Ottensmeier. Going forward, we can extend this understanding of whats going on in the blood in response to new viruses to understanding what goes on in the tissue when our immune system deals with cancer.

Ottensmeier and Vijayanand are working on further analysis of COVID-19 patients and also plan to expand their collaboration with the wider University of Liverpool community.

The study, titled, "Imbalance of regulatory and cytotoxic SARS-CoV-2-reactive CD4+ T cells in COVID-19," was supported the National Institutes of Health (grants U19AI14274, U19AI142742-0S1, U19AI118626, R01HL114093, R35-GM128938, S10RR027366, S10OD025052), the William K. Bowes Jr Foundation, the Whittaker Foundation, the Wessex Clinical Research Network and the National Institute of Health Research UK.

Additional study authors include co-first author Serena J. Chee, Anthony Kusnadi, Hayley Simon, Simon Eschweiler, Alba Grifoni, Emanuela Pelosi, Daniela Weiskopf, Alessandro Sette, Ferhat Ay and Grgory Seumois.

DOI:https://doi.org/10.1016/j.cell.2020.10.001

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About La Jolla Institute for Immunology

The La Jolla Institute for Immunology is dedicated to understanding the intricacies and power of the immune system so that we may apply that knowledge to promote human health and prevent a wide range of diseases. Since its founding in 1988 as an independent, nonprofit research organization, the Institute has made numerous advances leading toward its goal: life without disease.

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Every COVID-19 case seems different. These scientists want to know why. - Newswise

Immunology

Occupied with immunology and cancer, Merck KGaA hands off osteoarthritis drug to Novartis for 50M cash – Endpoints News

By the time Merck KGaA published promising Phase II data for sprifermin once tapped as a big prospect for the ailing R&D group late last year, the German drugmaker made clear it was looking for a partner to take over its whole osteoarthritis pipeline. While sprifermin is still sitting in the portfolio, its managed to find a buyer for another drug.

Novartis is paying 50 million upfront to license M6495, a Phase II-ready compound that targets an enzyme known as ADAMTS5, with promises of 400 million in milestones.

The deal comes more than three years after Merck KGaA grabbed the Nanobody from Ablynx since acquired by Sanofi with a 15 million payment to reward the preclinical proof-of-concept package. Then known as ALX-1141, the candidate was one of two to emerge from a collaboration dating back to 2011 to tackle osteoarthritis.

Since then Luciano Rossettis team has completed two Phase I studies for M6495, one in healthy volunteers and another in OA patients. With signs that the drug could cut down ARGS (a neoepitope from cleaved aggrecan, found in the synovial fluid and serum of OA patients) levels, the drug had potential in many different types of OA, he said.

The ultimate goal, of course, is to show it can protect against cartilage damage and reduce joint pain. But its now Novartis job to devise the trials needed to prove it.

With this deal we have found the right solution for this asset designed to present an innovative mechanism of action for the potential treatment of osteoarthritis, as we prioritize our pipeline to deliver the greatest impact for patients across our internal areas of expertise, Rossetti, head of global biopharma R&D, said in a statement.

Under Beln Garijo, whos stepping up as Merck KGaAs CEO, the priorities will likely revolve heavily around oncology, immunology and the intersection of the two.

For Novartis, OA falls under its focus on immunology, hepatology and dermatology. Its website lists two early-stage programs dedicated to the disease, one being an ANGPTL3 agonist designed to help regenerate cartilage. The Phase I study was completed in 2018 and a second trial is slate to wrap in 2022.

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Occupied with immunology and cancer, Merck KGaA hands off osteoarthritis drug to Novartis for 50M cash - Endpoints News

Immunology

Risk of Severe COVID May Depend on Your Type of Asthma, Experts Say – HealthDay News

WEDNESDAY, Oct. 7, 2020 (HealthDay News) -- Everyone agrees about the good news -- folks whose asthma is spurred on by allergies don't appear to have an increased risk of life-threatening illness if they contract COVID-19.

"Asthma has not risen as one of the top comorbid diseases for worse COVID-19 outcomes," said Dr. Sandhya Khurana, director of the Mary Parkes Center for Asthma, Allergy and Pulmonary Care at the University of Rochester (N.Y.) Medical Center. "We always worry with asthma and viral infections, because they seem to trigger asthma exacerbation unreasonably. But what we've seen so far is reassuring."

But debate continues to swirl regarding the potential severity of COVID infection in people with non-allergic asthma.

Some studies have suggested that people who have asthma caused by something other than allergies -- exercise, stress, air pollution, weather conditions -- might have an increased risk of severe COVID-19.

For example, Harvard researchers found that having non-allergic asthma increased the risk of severe COVID-19 by as much as 48%. That conclusion was based on data from 65,000 asthma sufferers presented in the June issue of the Journal of Allergy and Clinical Immunology.

"For those people, I think being more cautious would be good for them," said senior researcher Liming Liang, an associate professor of statistical genetics at the Harvard T.H. Chan School of Public Health in Boston. "I think the next wave is coming. We've got to be more cautious."

But other experts note that the data involving COVID and non-allergic asthma sufferers is very limited, and any conclusions that these folks are at higher risk of severe infection could be flawed.

Their asthma could be caused by other lung ailments that are associated with more serious cases of COVID, for instance, said Dr. Mitchell Grayson, chief of allergy and immunology at Nationwide Children's Hospital in Columbus, Ohio.

"There have been several studies that have shown that COPD does increase your risk of more severe disease," he said. "I don't think these studies have done a good job of excluding COPD in these patients."

Grayson agrees with Khurana that in the early days of the COVID-19 pandemic, there was much concern that asthma could be a risk factor -- a reasonable suspicion, given that the coronavirus attacks the lungs.

But everything that came out of the initial epidemic in China suggested that asthma was not a risk factor for life-threatening COVID, Grayson said, and the data continued to confirm that as the coronavirus spread across the globe.

"It's not there in the data. If it is there, it's extremely small risk. It's nothing I can see," he said.

Researchers have speculated that people with allergy-driven asthma might have some protection against COVID, due to the way the coronavirus infects the body.

The SARS-CoV-2 virus that causes COVID-19 enters lung cells by engaging with a type of protein on their surface called an ACE2 receptor, Khurana said.

"In the setting of an allergic type of inflammation, the expression of the ACE2 receptor appears to be downregulated. It appears to be lower. There's not as much receptor," she said.

Because there aren't as many ACE2 receptors available, people with allergic asthma might not be as vulnerable to severe infection, Khurana said. This theory also could help explain why other chronic diseases appear to increase COVID risk, she added.

"Patients in conditions like diabetes or hypertension, this receptor expression is increased," Khurana said. "That's a possible reason why those comorbid diseases are at especially high risk for this infection."

But that only explains why allergic asthma isn't a major risk factor for severe COVID, Grayson said. It doesn't explain why some studies are finding increased risk among people with non-allergic asthma.

Grayson suspects that the purported link between non-allergic asthma and COVID found in these studies is actually a link between a COVID and a host of different lung ailments, especially COPD.

"There are studies showing that COPD increases your risk of more severe COVID, not markedly but a little bit, not to the extent of things like hypertension and diabetes and [being] elderly," he said. "I'm concerned that what they're calling non-allergic asthma actually is COPD, which would skew their data."

In Khurana's view, more study is needed, particularly prospective studies that track people with different types of asthma prior to COVID infection.

"So far, we just don't know enough to make any conclusions. I think we're still scratching the surface here and still have a lot to learn," she said.

In the meantime, it would pay for everyone to protect themselves, Khurana added.

"It's good practice to observe the recommended guidance on hand hygiene and social distancing and masking and avoiding any situation where you could be exposed, even though it's obviously welcome to see that allergic asthma is not as high-risk as some of the other comorbid diseases," Khurana said.

More information

The American Academy of Allergy, Asthma and Immunology has more about COVID-19 myths.

SOURCES: Sandhya Khurana, M.D., director, Mary Parkes Center for Asthma, Allergy and Pulmonary Care, University of Rochester Medical Center, Rochester, N.Y.; Liming Liang, Ph.D., associate professor, statistical genetics, Harvard T.H. Chan School of Public Health, Boston; Mitchell Grayson, M.D., director, allergy and immunology, Nationwide Children's Hospital, Columbus, Ohio

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Risk of Severe COVID May Depend on Your Type of Asthma, Experts Say - HealthDay News

Immunology

IL-21 protein is a major part of immune response to chronic infections in the central nervous system – News-Medical.Net

Reviewed by Emily Henderson, B.Sc.Oct 6 2020

Researchers at Penn State College of Medicine now better understand the role of a protein, interleukin-21 (IL-21), in the immune system response to infections in the nervous system.

The results of their recent study support further investigation into using IL-21 as a therapeutic agent for persistent central nervous system infections.

CD4 T cells in the immune system produce IL-21, which is critical for the development of CD8 tissue-resident-memory (TRM) cells during persistent viral infections of the central nervous system with polyomavirus.

Dr. Aron Lukacher, professor and chair of the Department of Microbiology and Immunology, said the results, published in Science Immunology , demonstrate that IL-21 is an important factor in the development of effective immune responses to chronic infections in the central nervous system including neurodegenerative HIV-AIDS and progressive multifocal leukoencephalopathy (PML), a fatal brain infection caused by JC polyomavirus.

PML starts with symptoms including clumsiness, weakness or difficulty speaking or thinking. As it progresses, patients may develop dementia, have vision problems and become unable to speak.

Lukacher's lab created an animal model of JC polyomavirus in mice, called mouse polyomavirus (MuPyV). Their research focuses on strategies to reduce the harmful effects of MuPyV, with the goal of developing translational approaches to improving outcomes for patients with PML and other immunocompromising conditions.

Prior research demonstrated that IL-21 is a key part of immune responses in the body, but the present study investigated the specific mechanisms and role IL-21 plays in the immune response to infection with MuPyV.

The research team, including medical scientist training program student Heather Ren, studied mice that were unable to produce sufficient CD4 T-cells and had similar defects in gene expression related to the development of CD8 TRM cells. They found that injecting IL-21 into cerebrospinal fluid reduced those deficiencies.

The use of IL-21 as a therapeutic agent for persistent central nervous system infections needs further investigation. Whether it needs to be administered directly into the central nervous system or given peripherally, such as intravenous infusion, will require further testing in our model."

Dr. Aron Lukacher, Researcher and Professor, Chair of the Department of Microbiology and Immunology, Penn State College of Medicine

Lukacher said future studies will examine whether giving IL-21 to mice with persistent MuPyV infection, both under immunocompetent and CD4 T-cell-deficient conditions, may bolster protective antiviral CD8 T cell responses and keep the viral infection in check.

Source:

Journal reference:

Ren, H. M., et al. (2020) IL-21 from high-affinity CD4 T cells drives differentiation of brain-resident CD8 T cells during persistent viral infection. Science Immunology. doi.org/10.1126/sciimmunol.abb5590.

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IL-21 protein is a major part of immune response to chronic infections in the central nervous system - News-Medical.Net

Immunology

Vanderbilt researchers develop publicly available COVID-19 animal susceptibility prediction tool; suggests increased risk to horses – Vanderbilt…

A Vanderbilt team of experts in virology, genetics, structural biology, chemistry, physiology, medicine, immunology and pharmacology have together developed technology to understand and predict animal susceptibility to SARS-CoV-2, the scientific name for the strain of coronavirus causing COVID-19. providing evidence that horses and camels may be at increased risk of the virus. The group has also released a publicly available tool to enable people to understand the likelihood of other animals susceptibility.

The article, Predicting susceptibility to SARS-CoV-2 infection based on structural differences in ACE2 across species, was published in the Federation of American Societies for Experimental Biology (FASEB) Journal on Oct. 5.

The investigators applied a combination of sophisticated genetic sequence alignment and structural analysis of ACE2, the receptor protein for SARS-CoV-2, to a variety of known susceptible and non-susceptible species. Through the analysis they identified five particular amino acid sites within the protein that distinguish virus susceptibility or resistance, and using these sites developed an algorithm to predict susceptibility of unknown species. The algorithm has been made public on a website where people can upload the aligned ACE2 sequence of animals with unknown susceptibility to generate a COVID-19 susceptibility score.

Jacquelyn Brown, a staff scientist at the Vanderbilt Institute for Integrative Biosystems Research and Education, initiated the project. When I first learned that COVID-19 had crossed the species barrier into cats and dogs, I became worried about other animals that might act as reservoirs for the disease or be at risk, explained Brown, an avid equestrian who practices medieval mounted archery. Since MERS infects camels, I was concerned about what would happen if my horse could get it?! Horses have massive lungs and a sensitive respiratory system, and we humans often touch their noses and mouths.

206,000 horses live on horse farms and properties in Tennessee and 3.2 million of the states 10 million farm acres are devoted to the horse industry. Brown proposed a collaborative research project on the topic to Gordon A. Cain University Professor John Wikswo, who holds appointments in physics, biomedical engineering, and molecular physiology and biophysics.

As the director of VIIBRE, an institute established to foster and enhance interdisciplinary research in the biophysical sciences, bioengineering and medicine at Vanderbilt, Wikswo immediately assembled a trans-institutional team spanning Vanderbilt schools and colleges and Vanderbilt University Medical Center. I speak each disciplines language well enough to make the necessary connections, Wikswo said. This proved to be an outstanding group brought together by their interests and skills that produced an important result in very short order.

The project gave meaning to each researcher, at a time when we all were searching for ways to contribute to fighting COVID-19, noted Wenbiao Chen.

The work could not have been achieved without the collaboration of many researchers. The multidisciplinary approach revealed how much information can be wrung from the same basic information, noted Wenbiao Chen, the papers co-corresponding author and associate professor of molecular physiology and biophysics. We found potential targets by sequence comparison but wouldnt have been able to interpret our findings without structural information. The project gave meaning to each researcher, at a time when we all were searching for ways to contribute to fighting COVID-19.

Understanding the animals we should more closely scrutinize based on their susceptibility to COVID-19 can help us protect people, pets, wildlife, livestock and our food sources, said Matthew Alexander, assistant professor of medicine. The algorithm the team developed is particular to SARS-CoV-2 because it focuses on its particular receptor binding protein ACE2, but the approach is broadly applicable to predicting susceptibility to other viruses or during future outbreaks.

There is also the opportunity to investigate if the identified five sites on ACE2 that most distinguish susceptible from non-susceptible species can be used as targets to develop drugs that inhibit these sites specifically. I hope that our results will inspire future research on both rational drug design and closer examination of at-risk species, said Meena Madhur, the papers co-corresponding author, associate professor of medicine and associate director of the Vanderbilt Institute for Infection, Immunology and Inflammation at VUMC.

Of note, the work and collaboration were conducted remotely, with an analysis of publicly available data. This experimental approach of using extensive and rapidly accumulating publicly available data in new ways allowed us to efficiently answer a timely question without having to generate new datasets. The collaboration was fun and rewarding, and we were able to answer an important question that none of us could have solved alone, Alexander, the papers co-first author said. Wikswo pointed out that while the source data was public, the project required massive calculations of how different versions of the virus would bind to each animals ACE2.

Members of the collaborative project also include Distinguished Research Professor of Chemistry Jens Meiler, Clara Schoeder, co-first author and postdoctoral scholar, , Charles Duncan Smart, graduate student in molecular physiology and biophysics, Chris Moth, computational chemist in the biological sciences department, and Tony Capra, research associate professor of biological sciences.

The work was supported by National Institutes of Health grants F32HL144048-01, DK117147, UH3TR002097 and U01TR002383, U19AI117905, U01AI150739, and R01AI141661, R35GM127087, and DP2HL137166 and American Heart Association grants 20PRE35080177 and EIA34480023

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Vanderbilt researchers develop publicly available COVID-19 animal susceptibility prediction tool; suggests increased risk to horses - Vanderbilt...