Category Archives: Immunology

Immunology

Drug used to treat blood cancers might help reduce COVID-19 severity in patients: Study – Deccan Herald

Scientists have observed that a drug which is already approved to treat several blood cancers, is associated with reduced respiratory distress and a reduction in the overactive immune response in COVID-19 patients, an advance that may lead to a potential therapeutic for novel coronavirus infection.

According to the researchers, including those from the National Cancer Institute in the US, the cancer drug acalabrutinib blocked the protein Bruton tyrosine kinase (BTK) in COVID-19 patients, and provided clinical benefit to a small group of them.

The study, published in the journal Science Immunology, noted that the findings should not be considered clinical advice, and remain to be tested in a randomised, controlled clinical trial.

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The BTK protein, according to the scientists, plays an important role in the immune system, including in macrophages which are immune cells that can cause inflammation by producing proteins known as cytokines.

These proteins, the researchers said, act as chemical messengers that help to stimulate and direct the immune response.

In some patients with severe COVID-19, the study said a large amount of cytokines are released in the body all at once, causing the immune system to damage the function of organs such as the lungs -- a process known as a "cytokine storm."

The current study involved 19 patients with a confirmed COVID-19 diagnosis that required hospitalisation, as well as with low blood-oxygen levels and evidence of inflammation.

According to the scientists, 11 of the 19 patients had been receiving supplemental oxygen for a median of two days, and eight others had been on ventilators for a median of 1.5 days.

The study noted that within one to three days after they began receiving the cancer drug, majority of patients in the supplemental oxygen group experienced a substantial drop in inflammation, and their breathing improved.

It said eight of the 11 patients were able to come off supplemental oxygen, and were discharged from the hospital.

Although the benefit of acalabrutinib was reported to be less dramatic in patients on ventilators, the scientists said four of the eight patients were able to come off the ventilator, two of whom were eventually discharged.

According to the scientists, the ventilator patient group was extremely clinically diverse and included patients who had been on a ventilator for prolonged periods of time and had major organ dysfunction.

Two of the patients in this group died, they said.

An analysis of blood samples from the patients revealed that the levels of interleukin-6 (IL-6), a major cytokine associated with hyperinflammation in severe COVID-19, decreased after treatment with acalabrutinib.

The scientists said counts of lymphocytes, an immune cell type associated with worse outcome in COVID-19 patients, also rapidly improved in most patients.

When the researchers tested blood cells from patients with severe COVID-19, who were not in the study, and compared it with samples from healthy volunteers, they found that the patients with severe COVID-19 had higher activity of the BTK protein and greater production of IL-6.

Based on these findings, they suggested that acalabrutinib may have been effective since its target, BTK, is hyperactive in severe COVID-19 immune cells.

However, in a note of caution, the scientists also mentioned in the study that the most common adverse events associated with long-term acalabrutinib therapy included "low-grade headache, diarrhea, pyrexia and upper respiratory tract infections."

They said the safety profile of acalabrutinib in patients with severe COVID-19 needs to be confirmed in a prospective clinical trial.

"Further correlative studies will be needed to understand the basis for response or resistance to BTK inhibition in patients with such advanced disease," the scientists wrote in the study.

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Drug used to treat blood cancers might help reduce COVID-19 severity in patients: Study - Deccan Herald

Immunology

Resistance Genes to Latest Generation of Antibiotics Are Widespread – Technology Networks

The latest generation of tetracyclines a class of powerful, first-line antibiotics was designed to thwart the two most common ways bacteria resist such drugs. But a new study from researchers at Washington University in St. Louis and the National Institutes of Health (NIH) has found that genes representing yet another method of resistance are widespread in bacteria that live in the soil and on people. Some of these genes confer the power to destroy all tetracyclines, including the latest generation of these antibiotics.However, the researchers have created a chemical compound that shields tetracyclines from destruction. When the chemical compound was given in combination with tetracyclines as part of the new study, the antibiotics lethal effects were restored.

The findings indicate an emerging threat to one of the most widely used classes of antibiotics but also a promising way to protect against that threat.

We first found tetracycline-destroying genes five years ago in harmless environmental bacteria, and we said at the time that there was a risk the genes could get into bacteria that cause disease, leading to infections that would be very difficult to treat, said co-senior author Gautam Dantas, PhD, a professor of pathology and immunology and of molecular microbiology at Washington University School of Medicine in St. Louis. Once we started looking for these genes in clinical samples, we found them immediately. The fact that we were able to find them so rapidly tells me that these genes are more widespread than we thought. Its no longer a theoretical risk that this will be a problem in the clinic. Its already a problem.

In 2015, Dantas, also a professor of biomedical engineering, and Timothy Wencewicz, PhD, an associate professor of chemistry in Arts & Sciences at Washington University, discovered 10 different genes that each gave bacteria the ability to dice up the toxic part of the tetracycline molecule, thereby inactivating the drug. These genes code for proteins the researchers dubbed tetracycline destructases.

But they didnt know how widespread such genes were. To find out, Dantas and first author Andrew Gasparrini, PhD then a graduate student in Dantas lab screened 53 soil, 176 human stool, two animal feces, and 13 latrine samples for genes similar to the 10 theyd already found. The survey yielded 69 additional possible tetracycline-destructase genes.

Then they cloned some of the genes into E. coli bacteria that had no resistance to tetracyclines and tested whether the genetically modified bacteria survived exposure to the drugs. E. coli that had received supposed destructase genes from soil bacteria inactivated some of the tetracyclines. E. coli that had received genes from bacteria associated with people destroyed all 11 tetracyclines.

The scary thing is that one of the tetracycline destructases we found in human-associated bacteria Tet(X7) may have evolved from an ancestral destructase in soil bacteria, but it has a broader range and enhanced efficiency, said Wencewicz, who is a co-senior author on the new study. Usually theres a trade-off between how broad an enzyme is and how efficient it is. But Tet(X7) manages to be broad and efficient, and thats a potentially deadly combination.

In the first screen, the researchers had found tetracycline-destructase genes only in bacteria not known to cause disease in people. To find out whether disease-causing species also carried such genes, the scientists scanned the genetic sequences of clinical samples Dantas had collected over the years. They found Tet(X7) in a bacterium that had caused a lung infection and sent a man to intensive care in Pakistan in 2016.

Tetracyclines have been around since the 1940s. They are one of the most widely used classes of antibiotics, used for diseases ranging from pneumonia, to skin or urinary tract infections, to stomach ulcers, as well as in agriculture and aquaculture. In recent decades, mounting antibiotic resistance has driven pharmaceutical companies to spend hundreds of millions of dollars developing a new generation of tetracyclines that is impervious to the two most common resistance strategies: expelling drugs from the bacterial cell before they can do harm, and fortifying vulnerable parts of the bacterial cell.

The emergence of a third method of antibiotic resistance in disease-causing bacteria could be disastrous for public health. To better understand how Tet(X7) works, co-senior author Niraj Tolia, PhD, a senior investigator at the National Institute of Allergy and Infectious Diseases at the NIH, and co-author Hirdesh Kumar, PhD, a postdoctoral researcher in Tolias lab, solved the structure of the protein.

I established that Tet(X7) is very similar to known structures but way more active, and we dont really know why because the part that interacts with the tetracycline rings is the same, Kumar said. Im now taking a molecular dynamics approach so we can see the protein in action. If we can understand why it is so efficient, we can design even better inhibitors.

Wencewicz and colleagues previously designed a chemical compound that preserves the potency of tetracyclines by preventing destructases from chewing up the antibiotics. In the most recent study, co-author Jana L. Markley, PhD, a postdoctoral researcher in Wencewiczs lab, evaluated that inhibitor against the bacterium from the patient in Pakistan and its powerful Tet(X7) destructase. Adding the compound made the bacteria two to four times more sensitive to all three of the latest generation of tetracyclines.

Our team has a motto extending the wise words of Benjamin Franklin: In this world nothing can be said to be certain, except death, taxes and antibiotic resistance, Wencewicz said. Antibiotic resistance is going to happen. We need to get ahead of it and design inhibitors now to protect our antibiotics, because if we wait until it becomes a crisis, its too late.ReferenceGasparrini et al. (2020). Tetracycline-inactivating enzymes from environmental, human commensal, and pathogenic bacteria cause broad-spectrum tetracycline resistance. Communications Biology. DOI: https://doi.org/10.1038/s42003-020-0966-5

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Resistance Genes to Latest Generation of Antibiotics Are Widespread - Technology Networks

Immunology

New Study Outlines a Roadmap for Effective Treatment of COVID-19 – SciTechDaily

Study outlines key immunological factors underlying COVID-19 disease progression and proposes a range of drugs that may be repurposed to treat the disease.

Due to the devastating worldwide impact of COVID-19, the illness caused by the SARS-CoV-2 virus, there has been unprecedented efforts by clinicians and researchers from around the world to quickly develop safe and effective treatments and vaccines. Given that COVID-19 is a complex new disease with no existing vaccine or specific treatment, much effort is being made to investigate the repurposing of approved and available drugs, as well as those under development.

InFrontiers in Immunology, a team of researchers from the U.S. Food and Drug Administration review all of the COVID-19 clinical and research findings to date. They provide a breakdown of key immunological factors underlying the clinical stages of COVID-19 illness that could potentially be targeted by existing therapeutic drugs.

Dr. Montserrat Puigof the U.S. Food and Drug Administration, senior author of the review, stated that there are multiple factors involved in determining if the patients immune response will be insufficient or successful in combating the infection. Our review is an overview of these factors and how they can be considered to define the context in which medications currently used for other diseases, or development of novel agents, can be utilized to prevent, ameliorate or cure COVID-19.

We know that during the early stage of COVID-19 people can show no symptoms or mild symptoms, and for many the disease resolves.

For others it can be catastrophic. The illness can progress to a severe stage with manifestations including Acute Respiratory Distress Syndrome, accompanied by severe lung inflammation and damage. Patients with severe COVID-19 are often admitted to intensive care units and require life support with medical ventilation.

This review compiles and summarizes published up-to-date studies unraveling the factors leading to the cytokine storm and its consequences observed in COVID-19, including the immunological events underlying the severe manifestation of the disease.

The analysis is further supplemented with knowledge previously acquired from other coronaviruses including SARS-CoV and MERS-CoV.

The authors underscore key immunological events that might tip the balance from a protective to a hyperinflammatory response leading to life-threatening conditions. They outline a promising list of currently available drugs that are either under study or under consideration for use in COVID-19 based on their potential to influence these key immunological events.

These drugs include those that could inhibit SARS-CoV-2 entry into host cells, antivirals with the potential to block SARS-CoV-2 replication or factors that could boost the antiviral response, monoclonal antibodies targeting pro-inflammatory cytokines that drive the hyperinflammatory response and therapeutics that could improve the function of the lungs.

Puig states that approaches to therapy in the early stage of the disease will differ from those in its severe late stage. Adding that as the results of clinical trials become available, it may become increasingly clear that there is likely no single magic bullet to resolve the disease but a combination of several interventions that target different key factors of COVID-19 may well be required.

Puig cautions that the research and data obtained from COVID-19 studies are rapidly evolving and continuously updated. Thus, as clearly stated in our review, the information provided is a lessons learned to date and describes the knowledge available at the time of the publication of the review.

The description of the immunological profile of the clinical stages of COVID-19 provided in this review will enable more informed decisions about the type and timing of treatments to be evaluated in clinical trials.

Puig explains that our hope is that the information contained in our review will help professionals in COVID-19 research develop new tools and agents to better treat those at high risk of severe COVID-19.

Reference: Lessons learned to date on COVID-19 hyperinflammatory syndrome: considerations for interventions to mitigate SARS-CoV-2 viral infection and detrimental hyperinflammation by Marco Cardone, Masahide Yano, Amy S. Rosenberg and Montserrat Puig, 29 May 2020, ,Frontiers in Immunology.DOI: 10.3389/fimmu.2020.01131

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New Study Outlines a Roadmap for Effective Treatment of COVID-19 - SciTechDaily

Immunology

Distributed Bio Partners With Mediar Therapeutics, Inc. – Business Wire

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Distributed Bio, a global leader in computational optimization of fully human monoclonal antibody libraries, is pleased to announce a comprehensive research partnership with Mediar Therapeutics, a preclinical stage biotechnology company developing therapeutics to halt, or even reverse, fibrosis based in Cambridge, MA. Distributed Bio will use its SuperHuman2.0 Antibody Discovery platform to identify lead antibodies for Mediar programs.

Mediar selected Distributed Bio based on their industry-leading scientific technology and expertise in antibody discovery, says Dr Paul Yaworsky, CSO of Mediar. The platform is engineered to yield a truly diverse panel of fully human high affinity antibodies which enhance our ability to generate therapeutic candidates that match our selectivity, cross reactivity and developability requirements. Drug development is inherently a high-risk process. At Mediar we strive to take every measure to mitigate those risks. Partnering with Distributed Bio is one of those measures, and ultimately leads us to delivering lifesaving therapeutics faster and more efficiently.

We are delighted that Mediar selected Distributed Bio as a preferred partner for antibody discovery, says Dr Jacob Glanville, Co-Founder and Chief Executive Officer of Distributed Bio. The SuperHuman Platform represents the culmination of a decade of our research in computational library design. Weve recently demonstrated how effective and fast it is by generating a large panel of neutralizing antibodies against Covid-19 in a matter of weeks. The ultimate goal of everyone in the biotechnology industry is to improve patients lives as fast as possible. Our technologies represent an essential tool in that fight.

The SuperHuman2.0 antibody library of 76 billion sequence-unique antibodies offers a new paradigm in antibody discovery: hits to any target, with species cross-reactivity and selectivity that are crucial for success. The hits are H3-diverse, thermostabilized >70C, non-immunogenic, fully human, pre-screened by human blood and exist on 100% germline frameworks with robust therapeutic pedigrees to enhance developability, CMC, and human safety profiles. SuperHuman2.0 delivers an order of magnitude more molecules than can be generated by other technologies, and enables partners to search for ultra-specific, species-cross reactive therapeutic antibodies at unprecedented speeds. The library overcomes many of the limitations of other monoclonal generation technologies that has resulted in a unique engineering opportunity: a library that can generate diverse and developable hits against every antigen tested, enabling routine success against historically impossible or challenging antibody targets Covid-19, GPCRs agonists and antagonists, Ion Channels, pMHC complexes, broadly-neutralizing antibodies against HIV, therapeutic anti-idiotypic antibodies, bi-epitopic antibodies, ultra-selective antibodies that avoid related proteins, and mouse/NHP/human cross-reactive antibodies with low species homology.

About Distributed Bio

Distributed Bio is a computational immunoengineering biotechnology group, self-funded by the success of the stack of antibody discovery, optimization and analysis technologies to partners across the pharmaceutical industry. Our mission is to disrupt biologic engineering with big data, machine learning, and computational immunology-driven design.

From a team that includes inventors of antibody repertoire sequencing technologies, their AbGenesis antibody and TCR repertoire analysis and engineering platform enables partners to analyze antibody repertoires by high-throughput sequence, Sanger sequence, and functional assay without requiring large data center investments or local bioinformatics specialists. By using AbGenesis to analyze thousands of antibody repertoires and antibody libraries, they developed the computationally optimized SuperHuman2.0 antibody library, the SLiC single light chain library, the Tungsten humanized VHH library, CAR-T discovery library, and the Cosmic antibody library.

About Mediar Therapeutics

Mediar Therapeutics is a preclinical stage biotechnology company developing therapeutics to halt, or even reverse, fibrosis and restore long-term organ function. The platform and pipeline are based on an emerging class of novel targets fibrotic mediators that play key roles in modulating myofibroblast biology and the development of fibrosis in chronically damaged organs. Mediar was founded by Partners Innovation Fund, Massachusetts General Hospital and Brigham & Womens Hospital.

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Distributed Bio Partners With Mediar Therapeutics, Inc. - Business Wire

Immunology

Ive gotten a couple of dirty looks: When the coronavirus pandemic and spring allergy season align – The Boston Globe

Were still in the midst of a pandemic. At the same time, spring allergy season is upon us. As the two overlap, so too can a few mild symptoms brought on by each one, doctors say. The coincidental timing has made people hyper-aware of appearing ill when in public, as we approach Phase 2 of Governor Charlie Bakers reopening plan. For others, its left them wondering when they get that first sniffle or cough or headache if maybe theyre coming down with COVID-19.

As one Twitter user put it: Its a bad year to have an epically terrible allergy season.

The battle to hold back from coughing or sneezing within earshot of strangers has led to upping doses of allergy medications, or joking about carrying around signs that say, Its just allergies!" Some have felt the need to actually belt the phrase out loud, lest they give anybody around them the wrong impression.

Madeline Donohue, a tech consultant who lives in the Fenway, said, "The hardest part is if I get hit with a sneeze attack.

Its embarrassing because Im like, Im not sick!" she said.

Donohue said shes perfected a new skill to let people know that shes healthy: smiling with her eyes over her face mask, a look that says, Its just allergies, I swear.

Arlington resident Nick Gotch said the alignment of the pandemic and the layers of yellowish-green pollen now coating most surfaces outside has made it much more difficult than a usual allergy season."

Hes more reluctant to go out because people might think he has the virus, and "I dont really want to be a cause of concern, he said in a message to the Globe. The other thing ... [is] having a sudden allergy attack while wearing a mask is problematic.

For 42-year-old Mark Ajemian, an awkward situation unfolded while picking up takeout recently. As he waited for his order with a mask on, his allergies came on full force. He held it in. Then, before he could get his food, he had to rush outside.

I had a sneeze fit for like a minute and a half, he said. I went back inside, and everyone was staring at me like, Dont come near me. ... Honestly, I dont blame the people that are judging me.

While some allergic types have tried to stifle symptoms in public, others have been left playing a new game in their heads at the onset of them: Am I sick, or is that just nature at work?

According to the American College of Allergy, Asthma, and Immunology, allergy symptoms from exposure to different types of pollens can include sneezing, nasal congestion, runny nose, watery eyes, coughing, and wheezing.

When it comes to signs of possibly having COVID-19, at least a few of those symptoms cough, shortness of breath, congestion, or a runny nose are slightly similar.

Dr. Caroline Sokol, an attending physician with the allergy and clinical immunology department at Mass. General Hospital, said this can "definitely be confusing for some people, what theyre experiencing.

Symptoms of seasonal allergies are going to come across to some people as a viral infection or look like a viral infection, said Sokol, who is recovering from COVID-19 herself. Although a lot of people will say, I think this is my allergy symptoms, theres stress and anxiety over the fact that its hard to know the difference sometimes.

But several doctors who spoke with the Globe, including Sokol, made clear that there are key differences between the two, specifically a fever, diarrhea, muscle aches, and the sudden loss of smell without nasal congestion.

Sokol said when allergy patients have called concerned about what they might be dealing with, shes had them start allergy treatments immediately, because if its allergies, all those treatments will help pretty quickly.

If they dont, shell recommend further treatment or getting tested for the virus.

Omar Cabrera, a spokesman for the state Department of Public Health, said its certainly possible that symptoms of allergies can be similar to some of those of COVID-19, which is why officials generally recommend a low threshold for testing for the virus.

Even the presence of mild symptoms suggests the need for testing, Cabrera said in a statement. At this time the Commonwealth has capacity to test as indicated, and one purpose of diagnostic tests is to distinguish between conditions that may appear similar.

Dr. Daniel Kuritzkes, chief of the division of infectious diseases at Brigham and Womens Hospital, said because COVID-19 numbers are trending downward, it should be easier for people who have mostly stayed indoors up to this point, and also deal with allergies annually, to differentiate the two.

But for those who are suddenly overcome by a blast of pollen-related sneezes or coughs when finally stepping outside, its all the more reason to always be wearing a mask, he said.

Allergy sufferers could still be asymptomatic COVID-19 carriers.

You will be doing everybody a huge favor."

Steve Annear can be reached at steve.annear@globe.com. Follow him on Twitter @steveannear.

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Ive gotten a couple of dirty looks: When the coronavirus pandemic and spring allergy season align - The Boston Globe

Immunology

Dr. Princess U. Ogbogu named chief of Division of Allergy, Immunology, and Rheumatology at UH Rainbow – Crain’s Cleveland Business

Dr. Princess U. Ogbogu was named chief of the Division of Allergy, Immunology, and Rheumatology at University Hospitals Rainbow Babies & Children's Hospital, effective Aug. 1, according to a news release.

Ogbogu joins UH from Ohio State University, where she served as the director of the Division of Allergy and Immunology and as an associate professor of medicine since 2016. She has held various other leadership roles there and at Nationwide Children's Hospital since she was recruited to OSU in 2008.

"Dr. Ogbogu is a highly regarded physician and researcher, one of the nation's top experts in the field of allergy and immunology, with medical education roots in Cleveland," said Dr. Marlene R. Miller, pediatrician-in-chief at UH and chair of the Department of Pediatrics at Case Western Reserve University School of Medicine, in a provided statement. "We are excited to bring her leadership and expertise to our patients and families in Northeast Ohio and beyond."

Ogbogu is the principal investigator for ongoing IRB-approved studies on the topic of hypereosinophilic syndromes, asthma and COVID-19, according to the release. An active researcher, she has published in two scientific book chapters and dozens of peer reviewed articles.

Ogbogu earned her MD from Northeastern Ohio Universities College of Medicine and completed a residency in internal medicine at CWRU, as well as a fellowship in allergy and immunology at the National Institutes of Health in Maryland, according to the news release. She is currently a member of the American Board of Allergy and Immunology Board of Directors, serving a term from January 2019 through the end of 2021. She is also a member in a number of several American Academy of Allergy, Asthma, and Immunology (AAAAI) national committees, according to the release.

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Dr. Princess U. Ogbogu named chief of Division of Allergy, Immunology, and Rheumatology at UH Rainbow - Crain's Cleveland Business

Immunology

CSL Behring and Seattle Children’s Research Institute to Advance Gene Therapy Treatments for Primary Immunodeficiency Diseases – P&T Community

SEATTLE and KING of PRUSSIA, Pa., June 2, 2020 /PRNewswire/ --Seattle Children's Research Institute, one of the top pediatric research institutions in the world, and global biotechnology leader CSL Behring announced a strategic alliance to develop stem cell gene therapies for primary immunodeficiency diseases.

Initially, the alliance will focus on the development of treatment options for patients with two rare, life-threatening primary immunodeficiency diseases -- Wiskott-Aldrich Syndrome and X-linked Agammaglobulinemia. These are two of more than 400 identified primary immunodeficiency diseases in which a part of the body's immune system is missing or functions improperly.

"CSL Behring will collaborate with Seattle Children's experts to apply our novel gene therapy technology to their research pipeline, with an aim to address unmet needs for people living with certain rare primary immunodeficiency diseases," said Bill Mezzanotte, MD, Executive Vice President, Head of Research and Development for CSL Behring. "Expanding our gene therapy portfolio into an area of immunology well known to CSL exemplifies how we are strategically growing our capabilities in this strategic scientific platform and are collaborating with world class institutions to access innovation with the potential to vastly improve patients' lives."

"Stem cell gene therapies that correct the genetic abnormality driving a child's disease will transform the therapeutic options for children with Wiskott-Aldrich Syndrome, X-Linked Agammaglobulinemia and other immunodeficiency diseases,"said David J. Rawlings, MD, director of the Center for Immunity and Immunotherapies and division chief of immunology at Seattle Children's, and a professor of pediatrics and immunology at the University of Washington School of Medicine."The collaboration with CSL Behring supports our longstanding research programs for pediatric immunodeficiency diseases and will accelerate this research toward clinical trials, helping get these innovations to the children who need them."

CSL Behring researchers, working with researchers from Seattle Children's Research Institute, will investigate applying the proprietary platform technologies, Select+ and Cytegrity, to several pre-clinical gene therapy programs. These technologies, which have broad applications in ex vivo stem cell gene therapy, are designed to address some of the major challenges associated with the commercialization of stem cell therapy, including the ability to manufacture consistent, high-quality products, and to improve engraftment, efficacy and tolerability.

Wiskott-Aldrich Syndrome (WAS) has an estimated incidence between one and 10 cases per million males worldwide, according to the National Institutes of Health. WAS patients' immune systems function abnormally, making them susceptible to infections. They also experience eczema, autoimmunity and difficulty forming blood clots, leaving them vulnerable to life threatening bleeding complications. Today the only knowncurefor WAS is a stem cell transplant, if a suitable donor can be found.

X-linked Agammaglobulinemia (XLA) is another rare primary immunodeficiency in which patients have low levels of immunoglobulins (also known as antibodies), which are key proteins made by the immune system to help fight infections. Like WAS, XLA affects males almost exclusively, although females can be genetic carriers of the condition. While no cure exists for XLA, the goal of treatment is to boost the immune system by replacing missing antibodies and preventing or aggressively treating infections that occur, according to the Immune Deficiency Foundation.

About Seattle Children's

Seattle Children's mission is to provide hope, care and cures to help every child live the healthiest and most fulfilling life possible. Together, Seattle Children's Hospital, Research Institute and Foundation deliver superior patient care, identify new discoveries and treatments through pediatric research, and raise funds to create better futures for patients.

Ranked as one of the top children's hospitals in the country by U.S. News & World Report, Seattle Children's serves as the pediatric and adolescent academic medical center for Washington, Alaska, Montana and Idaho the largest region of any children's hospital in the country. As one of the nation's top five pediatric research centers, Seattle Children's Research Institute is internationally recognized for its work in neurosciences, immunology, cancer, infectious disease, injury prevention and much more. Seattle Children's Hospital and Research Foundation works with the Seattle Children's Guild Association, the largest all-volunteer fundraising network for any hospital in the country, to gather community support and raise funds for uncompensated care and research. Join Seattle Children's bold initiative It Starts With Yes: The Campaign for Seattle Children's to transform children's health for generations to come.

For more information, visit seattlechildrens.org or follow us on Twitter, Facebook, Instagram or on our On the Pulse blog.

About CSL Behring

CSL Behring is a global biotherapeutics leader driven by its promise to save lives. Focused on serving patients' needs by using the latest technologies, we develop and deliver innovative therapies that are used to treat coagulation disorders, primary immune deficiencies, hereditary angioedema, inherited respiratory disease, and neurological disorders. The company's products are also used in cardiac surgery, burn treatment and to prevent hemolytic disease of the newborn. CSL Behring operates one of the world's largest plasma collection networks, CSL Plasma. The parent company, CSL Limited (ASX:CSL;USOTC:CSLLY), headquartered in Melbourne, Australia, employs more than 26,000 people, and delivers its life-saving therapies to people in more than 70 countries. For more information, visit http://www.cslbehring.com and for inspiring stories about the promise of biotechnology, visit Vita http://www.cslbehring.com/Vita.

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Immunology

Dr. Amir Bajoghli’s Article on Shiitake Mushroom Dermatitis Featured in Premier Immunology Publication – IT Business Net

MCLEAN, VA / ACCESSWIRE / May 29, 2020 / The shiitake is an edible mushroom native to East Asia. The popularity of these mushrooms has increased over the years in the United States and with it has been a rise in allergic skin reactions to this relatively new ingredient on the American culinary landscape.

Shiitake flagellate dermatitis, also known as toxicoderma, is an allergic reaction related to the ingestion of raw or undercooked shiitake mushrooms. Signs of this dermatologic condition include skin eruptions resembling scratch or whiplash marks. This skin reaction occurs in approximately 2-3% of people who eat undercooked or raw shiitake mushrooms.

Various theories exist as to how and why this type reaction occurs with some people who eat the undercooked forms of the edible fungus.

When Dr. Amir Bajoghli of Skin & Laser Dermatology Center recently treated such a case in his practice, he realized it was of importance to share his medical findings regarding the patient with the scientific community. He wrote up the details of this Shiitake mushroom dermatitis. These findings were published in the Annals of Allergy, Asthma & Immunology, the premier publication for allergic and immunologic diseases.

Dr. Bajoghli is honored to publish the case with his father, Dr. Mehdi Bajoghli, a practicing allergist in Northern Virginia.

Dr. Amir Bajoghli has been active in the practice of dermatology and laser surgery since the completion of his training at the combined Tufts University and Boston University. He regularly presents lectures to other physicians regionally and internationally, and teaches medical students and dermatology residents at Georgetown University.

Dr. Amir Bajoghli can be reached at either of his Virginia offices:

McLean:1359 Beverly Rd., 2nd FloorMcLean, VA 22101(703) 893-1114

Woodbridge:2200 Opitz Blvd., Suite 100Woodbridge, VA 22191(703) 492-4140

SOURCE: Skin and Laser Dermatology Center

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Dr. Amir Bajoghli's Article on Shiitake Mushroom Dermatitis Featured in Premier Immunology Publication - IT Business Net

Immunology

Why AbbVie Could Have the Most Upside Among Big Pharma Stocks – 24/7 Wall St.

Healthcare Business

Jon C. Ogg

Some mergers can add a nice shot in the arm for an acquirer. After years of being focused on Humira, AbbVie Inc. (NYSE: ABBV) has now completed its acquisition of Allergan Inc. (NYSE: AGN), which brings existing sales and an additional product pipeline down the road.

Analysts on Wall Street in general have issued higher upside projections ahead of and in the wake of this mergers completion. While SVB Leerink may have the highest analyst target price on AbbVie of $122, the independent research firm Argus has issued one of the highest price targets that has been seen in some time.

24/7 Wall St.s top analyst calls of the day included that Argus raised its rating to Buy from Hold and offered a $115 price target. This target is handily higher than Refinitivs $97.00 consensus price target. While this is one of the most aggressive calls in the stock, it also would represent more upside than has been seen in the other major pharma and mega-cap biotechs.

The difference between an independent research firm like Argus and a traditional brokerage firm with underwriters is that Argus gets no investment banking fees from the companies. Investors should understand that AbbVies new Buy rating is a shorter term call. The firm was quick to point out that its long-term rating is Hold.

After completion of the merger with Allergan, Argus noted that the portfolio expansion includes a growing oncology franchise that is anchored by Imbruvica and Venclexta. It also noted Skyrizi and Rinvoq as two growth drivers in the immunology space. Allergan is said to add strengths in medical aesthetics, neuroscience, eye care and womens health.

One other issue to consider is that Allergan shares and its consensus price target are both still lower than when it was named among 20 undervalued ESG stocks. That call was right before the major sell-off turned into the instant recession under COVID-19.

Argus also sees AbbVie generating substantial cash flow that supports the dividend with its 5%-plus yield. The cash flow is also said to support developing, acquiring and collaborating on new product candidates for the future. The Argus report said this:

AbbVies merger with Allergan (completed in May) provides the combined company with an expanded portfolio of commercial products along with additional pipeline products that should help to drive future growth. Allergans portfolio is anchored by Botox, which has both aesthetics and therapeutic indications (such as migraine). In addition, two recently launched immunology drugs (Skyrizi and Rinvoq) are gaining traction and market share in their respective indications. These drugs, which are posting stronger sales than we had expected, complement Humira in autoimmune indications.

There are other blockbusters in the Allergan and AbbVie mix to consider here. The Argus report further said:

The company also has a growing oncology franchise, anchored by Imbruvica and Venclexta, both of which have become blockbuster products. Imbruvica and Venclexta together generated more than $5.2 billion in sales in 2019. Venclexta is growing sales at a more than 100% annual rate (reaching $317 million in Q1-2020), reflecting approval for additional indications. In addition to the strong product portfolio, we note that the stock carries a yield of about 5.1%, which we view as very attractive during a period of market volatility and economic uncertainty.

Tuesdays new analyst call is much stronger than most analysts give (in the 8% to 10% range) in new ratings for Dow Jones industrials or S&P 500 companies. The Argus call projects 26% upside, before even getting into the 5% dividend yield for total return investors.

AbbVie shares traded up 0.4% at $91.10 on Tuesday. Its 52-week range is $62.55 to $97.86.

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Why AbbVie Could Have the Most Upside Among Big Pharma Stocks - 24/7 Wall St.

Immunology

Viola Ventures is Seeking Technologies that Combine AI and Fundamental Scientific Disciplines – CTech

Zvika Orron, a partner at Israeli early-stage venture capital firm Viola Ventures, is clearly a big believer in the potential of computational biology. So much so that he believes the AI disruption proven in traditional industries such as the automotive industry that led to the huge success story of Mobileye, which in 2017 was acquired by Intel for $15.3 billion in the largest deal Israel's tech industry has seen to date, could potentially repeat itself in the biology space.

One company hoping to one day be the next Mobileye is Israeli startup Immunai. Orron was part of the Viola and TLV Partners team that earlier this month led the companys $20 million seed round.

"The volume of data generated through modern biological research is growing exponentially and opening a great opportunity to leverage AI for providing deeper and more accurate insights to solve complex problems at a faster pace," said Orron.

Immunai was founded in January 2019 by Noam Solomon (CEO) and Luis Voloch (CTO) who were joined by Ansuman Satpathy, a professor of cancer immunology at Stanford University, Danny Wells, a current member of the Parker Institute for Cancer Immunotherapy, and Dan Littman, a professor of molecular immunology at New York University, all three of whom joined the team as founding scientists.

Immunai is developing a technological platform that aims to map the entire immune system for better detection, diagnosis, and treatment of disease, which according to Orron has the potential to disrupt the entire pharmaceutical ecosystem.

"Mobileye is an example of how AI technology, in this case, computer vision, can disrupt an entire industry. Mobileye could have just settled for providing computer vision services to camera companies or sold its computer vision as standalone software. But instead, it chose to develop an entire end-to-end system and disrupt the auto industry. Immunai also wants to cause disruption throughout the pharma industry with its AI solution by not only providing the immune system profiling but leveraging the data as a first step to pull out insights and provide a platform that will enable a range of applications. The companies are very similar to each other in that way," Orron told CTech earlier this week. "The second similarity is that both are trying to solve multi-disciplinary problems. Mobileye needs algorithm developers, hardware developers, as well as physicists, as it is trying to solve a very complex problem. And on top of that, you need someone to bring this all together with quality system engineering and make sure it works. If there is one thing that Israel is blessed with it is system engineers. That ability to combine different disciplines and turn them into a product with the right performance and place it on the right course is essential, as is the multidisciplinary factor. With Immunai you have three disciplines that must all work together. There are the biologists who analyze the data in the lab, there is the computational biology layer and on top of that, there is the layer of AI."

Orron explained that the working premises in biology are currently fairly established and now with AI it is possible to take these premises and prove them on more use cases and diseases.

"In any basic blood test you can identify many unique elements in our immune system. Immunai essentially profiles a person's immune system,"

Orron said. "And if you know all about someone's immune system you can, in theory, identify different diseases or you can, for example, tell an oncology patient which treatment is best for them, also known as companion diagnostics. You can also help the pharma companies move a lot faster in their clinical trials and ultimately develop drugs quicker."

Leveraging single-cell technologies and machine learning algorithms, Immunai has mapped out millions of immune cells and their functions, building the largest proprietary data set in the world for clinical immunological data.

"Biology expertise is becoming more and more granular and when looking for the best researchers in the world, founders may need to look outside the Israeli market. But in today's world you can set up a global company in which the AI tech could come from Israel and the biological research from across the globe," added Orron. "In Immunai's case, the founders are mathematicians by training and they joined forces with biologists from Stanford and the Parker Institute in New York. We are seeing more and more AI entrepreneurs turning their sights to the field of biology and partnering with researchers outside of Israel."

The emergence of the coronavirus (Covid-19) pandemic combined with the ever-declining cost of DNA sequencing has put companies of the likes of Immunai in prime position to establish themselves in the post-corona world.

"The price of DNA sequencing is decreasing exponentially and regulation is always evolving. During the era of Covid-19 all kinds of regulatory elements were eased in order to reach a vaccine as quickly as possible. Once these two developments coincide there is suddenly a lot of data available as many clinical trials are taking place. And this allows AI to enter the picture and help accelerate the development of medicines and new diagnostic tools," said Orron. "Medicine is currently the ideal place for AI, both from a financial and a technological standpoint."

Orron added that Viola's interest in computational biology is rapidly expanding and that it is also on the lookout for innovative AI solutions combining computer science with other fundamental scientific disciplines.

"We really believe in computational biology and we want to continue and invest in this field. Israel is very new to this field, with the U.S. for example far more advanced. But this is the time to invest in Israel because we are seeing many quality entrepreneurs looking in this direction. There is great potential in Israel. We are also checking out other fields in which there is a combination of computer science with other scientific disciplines like chemistry, physics, or biology. Specifically, we want to see how AI can accelerate a known scientific phenomenon and enable business driven solutions. Right now, most of our focus is on physics and biology. In physics, for example, we are looking at the world of quantum computing which combines computer science with physics. We really believe in this multidisciplinary thesis of combining fundamental science with computer science."

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Viola Ventures is Seeking Technologies that Combine AI and Fundamental Scientific Disciplines - CTech