Category Archives: Immunology

Stanford Awards for 2021-22 Academic Year Include Many DOM Faculty and Residents

Congratulations to the more than 40 recipients of awards for excellence in teaching, patient care, and more that were given out recently by Stanford Medicine in recognition of outstanding contributions during the 2021-2022 academic year. See the partial list (including many of our DOM colleagues) below.

Tracy Rydel, MD, clinical associate professor of primary care and population health, received the Henry J. Kaiser Family Foundation Teaching Award for Outstanding and Innovative Contributions to Medical Education.

Daniel Bernstein, MD, the Alfred Woodley Salter and Mabel G. Salter Endowed Professor in Pediatrics;Lars Osterberg, MD, professor of primary care and population health, andHolly Tabor, PhD, associate professor of primary care and population health, received the Henry J. Kaiser Family Foundation Award for Excellence in Preclinical Teaching.

Gordon Gao, MD, clinical assistant professor of medicine,Andre Kumar, MD, clinical assistant professor of medicine, andMo Mertaban, MD, clinical assistant professor of pediatric hospital medicine, received the Henry J. Kaiser Foundation Award for Excellence in Clinical Teaching.

Ara Ko, MD, assistant professor of surgery,An Diem La, MD, clinical assistant professor, andBenjamin Laniakea, MD, clinical assistant professor of primary care and population health, received the Arthur L. Bloomfield Award in Recognition of Excellence in the Teaching of Clinical Medicine.

Mina Charon, MD, clinical assistant professor of primary care and population health, received the Outstanding Community Clinic Preceptor, Clinical Instruction Award.

Pedram Fatehi, MD, clinical associate professor of nephrology, received the Award for Excellence in Promotion of Humanism.

Lisa Chamberlain, MD, professor of pediatrics, andErika Schillinger, MD, clinical professor of primary care and population health, received the Award for Exceptional Community Service.

Medical residents Jonji Barber, MD, Andrew Brennan, MD, Dylan Lukato, MD, Ria Pal, MD, Derek Smith, MD, and Celeste Witting, MD, received the Arnold P. Gold Foundation Award for Humanism and Excellence in Teaching. The award is given to residents based on their commitment to teaching and the compassionate treatment of students, colleagues and patients and their families.

Preetha Basaviah, MD, clinical professor of primary care and population health,Jon Bernstein, MD, PhD, professor of pediatrics,Cynthia DeTata, MD, clinical assistant professor of obstetrics and gynecology,Kimberly Harney, MD, clinical associate professor,Wilma Lee, MD, clinical assistant professor of obstetrics and gynecology,Fernando Mendoza, MD, associate dean of minority advising and programs, andCharles Prober, MD, professor of pediatrics, microbiology and immunology, received the Oscar Salvatierra Award for Exceptional Service to Stanford Medical Students and the School of Medicine.

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Awards and Honors: Summer 2022 | Department of Medicine News - Stanford Medicine

Immunology

What to Know About the Latest Advances in Managing Severe Asthma – TIME

June 25, 2022 medical

Graphs and charts dont always tell the whole story. Numbers can be deceiving. But anyone who looks at U.S. trends in asthma mortality can see, without squinting, that things are moving in the right direction.

A 2019 analysis in the American Journal of Respiratory and Critical Care Medicine found that from 1999 to 2015, asthma mortality fell by 43%. The decrease in asthma-related mortality was consistent in both sexes and in all race groups, with the largest decrease in patients older than 65 years, the authors concluded. Figures from the U.S. Centers for Disease Control and Prevention indicate that these positive trends have continued through 2019, and data coming from the U.K. and Europe tell a similarly happy tale.

What I see in the clinic today is completely different than it was 10 years ago, says Dr. Christopher Brightling, a clinical professor in respiratory medicine at the University of Leicester and a senior investigator at the National Institute for Health and Care Research in the U.K. The treatment space is looking really positive, and with the newest drugs I would anticipate responses to be even better.

Biologics, he and others say, are leading the way in the fight against severe asthma. These drugs work by manipulating the activity of genes or cells, and they have been life-changing for many patients. New advancements in inhaler-based medicines and connected technologies are other bright spots, and some health systems are moving their care teams out of the clinic and into community settings in an effort to reach underserved populations.

Together, these and other new advancements are producing real and measurable improvements in patient access and outcomes. It is really a very exciting time in asthma research right now, says Dr. Derek Chu, an assistant professor of medicine and a researcher in allergy and clinical immunology at McMaster University in Canada. Theres a lot in development for both mild and moderate-severe asthma.

Here, Chu and other experts detail the latest on these groundbreaking treatments and strategies.

Read More: How Alternative Medicine Can Help People With Asthma

In 2003, the U.S. Food and Drug Administration (FDA) approved the first biologic for the treatment of severe asthma. That drug, omalizumab, is a monoclonal antibody therapy that works primarily by reducing blood levels of IgE, an immune system antibody that contributes to airway inflammation among people with severe asthma.

Although omalizumab was revolutionary, experts say the past few years have witnessed the arrival of newer and better biologics that have all but eradicated the burden of severe asthma for most patients. These have been totally transformational, says David Jackson, a respiratory medicine specialist at Kings College London. Since 2017, a new biologic has been added to our armory on almost an annual basis, and the number of patients with uncontrolled asthma has gotten smaller and smaller.

Whereas the first biologics blocked IgE, the latest drugs in this category targetwith greater and greater precisionthe specific immune pathways and cells that drive asthma-related inflammation and symptoms. Cells called eosinophils are a hallmark of severe asthma, and these newer biologic therapies can dampen down their production and related pathways in a much more targeted way, Jackson says. He uses a military analogy to highlight the effectiveness of the newest biologics. These are like precision-guided laser bombs, as opposed to the old B52s dropping bombs from 50,000 ft. and just hoping for best.

Some of the newest biologics take aim at two specific immune system proteins: thymic stromal lymphopoietin (TSLP) and interleukin 33. These two activate cells in the airways, which leads to a release of all these [inflammation] players, Brightling explains. Because these two are farther upstream than some of the pathways targeted by older biologics, mellowing their activity may produce broader benefits, he says.

Biologics do come with downsides. For one thing, theyre expensive. They often cost around $30,000 a year in the U.S., Jackson says. They are not always covered by insurance. Also, in the past their administration required regular office or clinic visits. Biologics are traditionally delivered via injection anywhere from once every two months to once every two weeks. However, the coronavirus pandemic has helped shift the use of these drugs away from the clinic and into the home. Theres been a big push to self-administration, Jackson says. What we normally do now is to start in the clinicso give the first one to three administrations herethen go to home administration when its clear the patient is doing well.

Despite any lingering financial and logistical hurdles, the benefits provided by biologics are often profound. The latest and greatest biologics work so well that many patients are effectively relieved of the burden of severe asthma attacks or symptomssomething that would have seemed unbelievable just a decade ago.

Unfortunately, not everyone who would benefit from these drugs is getting them. Awareness of this medicine is not what it should be, Jackson says. A lot of patients continue to have asthma attacks and their doctor hasnt picked up on the fact that there are newer therapies. If every clinician who treats severe asthma was up to speed on these drugsand if everyone who truly needs them had access to these medicinesits possible that virtually every person with severe asthma could avoid the worst symptoms, he says.

Read More: The Breathing Technique a Navy SEAL Uses to Stay Calm and Focused

Asthma used to be thought of as a single disease that could range from mild to severe. But thats changed. The model of asthma as a single entity is now obsolete due to an increased understanding of its underlying heterogeneity, wrote the authors of a 2019 study in Clinical Reviews in Allergy & Immunology.

At this point, asthma is an umbrella term for a number of related but distinct diseases that are differentiated in part by the activation of various immune pathways. Those pathways are now better mapped than ever before. By identifying the ones driving pathology in an individual patienta process often called phenotypingclinicians can better predict how that person will fare on a drug. The phenotyping piece has been one of the big shifts, Brightling says. It can help us understand which patients will respond best to a treatment.

Phenotyping often starts with an assessment of a patients demographic or symptom characteristics. Is the person old or young? Do they have early-onset or late-onset asthma? Are they obese? Do they have atopic involvement? In the near futureand this is where some of the latest advancements have occurredphenotyping may involve blood and breath tests. Brightling says blood tests can provide helpful information on eosinophils and other immune system players that give rise to a persons asthma symptoms. Breath tests of exhaled nitric oxide can reveal the involvement of specific immune system proteins, as well as the presence of airway hyperactivity, he adds.

To be effective, the newest treatments have to find their way to the patients who will benefit from them most. Phenotyping plays a crucial matchmaking role.

Every asthma specialist knows that getting patients to reliably take their medicine can be a struggle. Particularly among young people with severe asthma, adherence is often poor. A 2018 study in the European Respiratory Journal found that even after special educational courses in inhaler use and disease management, only 63% of people with severe asthma adhered to their treatment plan.

I think one of the biggest challenges, especially with severe asthma, is that patients feel fine a lot of the time, and its difficult to remember to take a medication every single day if youre feeling good, says Dr. Ruchi Gupta, a professor of pediatrics, preventive medicine, and medicine (allergy and immunology) at Northwestern Universitys Feinberg School of Medicine and Lurie Childrens Hospital. Other experts say that pricey biologics might be needed far less if more patients with severe asthma reliably took their inhaled corticosteroids.

Theres a new solution to this problem: smart inhalers that can notify patients or their care team when doses are missed. For a 2021 study in Pediatrics, Gupta and her colleagues examined the usefulness of inhalers equipped with Bluetooth connected technologies among children with asthma. The inhalers notified a childs care team if they missed their daily doses several days in a row, or if they took too many rescue doses in a single day. After 12 months of follow-up, treatment adherence had increased by 17% and measures of asthma-symptom burden had likewise improved, the study found. Patients felt like someone was looking out for them and taking care of them, Gupta says.

Some of these smart-inhaler technologies are already available (though usually not covered by insurance). For example, patients can buy inhaler sensors that will remind them when to take their meds. Some health care systems have also set up office notifications similar to the type Gupta and her team studied. But for the most part, these new technologies are not widely deployed. My dream is that every time a patient uses their inhaler, this information would go straight into their electronic medical chart, she says. I know some groups are working on that.

One of the persistent challenges of modern medicine is ensuring the equitable distribution of quality care. Gupta mentions drug costs, Medicare and Medicaid coverage, and access to asthma specialists as some of the barriers between patients and the treatment they need.

In an effort to provide quality care to underserved groups, some asthma specialists are leaving the clinic and meeting patients where they live and work. Doctors here in Chicago are going out into the community and setting up tents where people know theyll be, or going to schools and giving checkups in parking lots, Gupta says.

She also mentions the asthma vans that are now operating in Chicago. These clinics on wheels, staffed by allergy specialists, drive to underserved communities and offer on-site treatment. These have been very effective resources, she says. More solutions like this are needed to improve access to appropriate asthma care.

Read More: How Climate Change and Air Pollution Affect Kids Health

Theres a lot more going on in the field of severe asthma care. For a 2021 study in JAMA, Chu found that triple-drug therapyadding a third medication to the common two-drug combination of corticosteroids and bronchodilatorsled to a lower incidence of severe attacks among patients who use inhalers.

Although the future looks bright, he says that more work lies ahead. The main issues are the critical need for head-to-head studies of active drugs or management approaches, rather than purely placebo-controlled studies, he says. This work could further clarify best treatment approaches.

However, life for many people with severe asthma has never been better. Many patients almost feel like they dont have the disease anymore, says Jackson. They stop having attacks, stop showing up in hospitals, and can function without asthma interfering in their life. Thats worth celebrating.

A mother’s blood may carry the secret to one type of autism – EurekAlert

June 25, 2022 medical

Autism is a neurodevelopment condition affecting 1 in 44 children in the U.S. It has a wide range of characteristics with different intensities and causes. One type of autism is maternal autoantibodyrelated autism spectrum disorder (MAR ASD).

MAR ASD is marked by the presence of specific maternal immune proteins known as autoantibodies that react to certain proteins found in the fetal brain. The maternal autoantibodies (IgG) cross the placenta and access the developing brain. Once there, they may cause changes in the way the brain develops in the offspring, leading to behaviors linked to autism.

Two new UC Davis MIND Institute studies are expanding our understanding of this type of autism. They found support for predictive protein patterns in the blood of expecting mothers and links of MAR ASD to higher intensities of autistic traits.

MAR ASD patterns linked to autism before birth

The MIND Institutes Judy Van de Water and a team of researchers showed that autoantibody binding to nine specific combinations of proteins (known as MAR ASD patterns) successfully predicts autism in previously diagnosed children. They tested maternal blood samples collected during pregnancy to see if they could validate the identified patterns. They wanted to see if the patterns accurately predicted autism in the children. Their study findings were published in Molecular Psychiatry.

Previously, we identified nine patterns linked to MAR ASD. In this study, we wanted to check the accuracy of these patterns in predicting MAR ASD. To do that, we tested plasma from pregnant mothers, collected by the Early Markers for Autism (EMA) study, said Van de Water, the studys senior author. Van de Water is a UC Davis professor of immunology and neurodevelopment.

The study screened the plasma of 540 mothers of autistic children, 184 mothers of kids with intellectual disability but no autism, and 420 general population mothers of kids with no known autism or intellectual disability at the time of the study.

It found reactivity to at least one of the nine MAR ASD patterns in 10% of the autistic group. This is compared with 4% of the intellectual disability group for some patterns, and 1% of the general population group. Four patterns were present only in mothers whose children were later diagnosed with autism, making those particular autoantibody patterns highly predictive.

The study also found that a mother with reactivity to any one of the nine MAR ASD patterns has around 8 times the chance of having an autistic child.

Several MAR ASD patterns were strongly associated with autism with intellectual disability. Others were linked to autism without intellectual disability. The protein pattern most strongly linked to autism was (CRMP1+CRMP2). It increased the likelihood of an autism diagnosis by 16 times and was not found in the non-autism groups.

MAR ASD similarly present across states

Previous research found the MAR subtype of autism in 20% of a Northern California sample of autistic kids Yet, until now, this type of autism has not been studied in any state besides California.

A team of researchers led by Kathleen Angkustsiri explored MAR ASD in two new clinical sites: the Childrens Hospital of Philadelphia (CHOP) and Arkansas Childrens Hospital and Research Institute (ACHRI). Their study, published in The Journal of Developmental and Behavioral Pediatrics, recruited 68 mothers of autistic children ages 2-12 years. The mothers provided blood samples and completed behavioral questionnaires about their children.

The study also included data from the children's clinical diagnostic assessments. It used established diagnostic measures known as ADOS (the autism diagnostic observation schedule) and Social Communication Questionnaire (SCQ) to assess the childrens autistic characteristics.

MAR ASD was present in 21% of CHOPs and 26% of ACHRIs samples. Overall, 23.5% of the blood samples were considered MAR positive (+MAR), showing autoantibodies reacting to known MAR ASD protein patterns.

Our study showed similar MAR ASD frequencies in two other states similar to what we observed in Northern California, Angkustsiri said. Angkustsiri is an associate professor of developmental-behavioral pediatrics at UC Davis Children's Hospital and the UC Davis MIND Institute and the studys lead author. This suggests that the prevalence of MAR ASD is consistent across different demographics and geographic settings.

MAR ASD and autism characteristics

The study also examined the link between MAR ASD and autism severity. It showed that children of mothers with +MAR antibodies had higher autism severity scores than those of -MAR mothers. It did not find significant differences in their IQ, adaptive function or unusual behavior.

MAR ASD positivity may be linked to more severe autism behaviors, Angkustsiri said. Both the SCQ reported by parents and the ADOS assessed by clinicians supported these findings.

Further study is needed to understand why mothers develop these antibodies and how long these antibodies may persist. Testing for MAR ASD patterns can be used to assess the probability of a child having autism before characteristics are present. The researchers aim to develop an accurate clinical test to provide clinicians with more tools for an earlier diagnosis of ASD.

We hope our work can help develop better-tailored services based on the type of autism and the child's strengths and specific challenges, Van de Water said.

###

Co-authors on Van de Waters study are Alexandra Ramirez-Celis, Joseph Schauer and Paul Ashwood from UC Davis, Lisa Croen, Cathleen Yoshida and Stacey Alexeeff from Kaiser Permanente, and Robert Yolken from Johns Hopkins University. Funding was provided by the NIEHS Center for Childrens Environmental Health and Environmental Protection Agency (EPA) grants (2P01ES011269-11, 83543201), the NIEHS-funded EMA study (R01ES016669), the NICHD-funded IDDRC (P50HD103526) and Consejo Nacional de Ciencia y Tecnologia (CONACYT- UC MEXUS) Doctoral Fellowships.

Co-authors on Angkustsiris study are Jill Fussell, Amanda Bennett, Joseph Schauer, Alexandra Ramirez-Celis, Robin Hansen and Judy Van de Water. The study was funded by the DBPNet Young Investigator Award UT5MC42432 and the NICHD-funded IDDRC (P50HD103526)

The authors recognize that medical terms such as symptom and severity are pathologizing and are making efforts to move away from this historical terminology. In this paper, the analysis is based on the calibrated severity score generated from the use of the diagnostic test the ADOS, which is why theyre using them in this instance.

Molecular Psychiatry

Maternal autoantibody profiles as biomarkers for ASD and ASD with co-occurring intellectual disability

26-May-2022

Judy Van de Water has patents issued for this technology and has founded a UC Davis startup company to develop this technology. The remaining authors have no conflicts of interest.

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

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A mother's blood may carry the secret to one type of autism - EurekAlert

Immunology

Dried samples of saliva and fingertip blood are useful in monitoring responses to coronavirus vaccines – EurekAlert

June 15, 2022 medical

Based on an antibody study, dried samples of easily self-collected saliva and of blood drawn from the fingertip could be useful for monitoring peoples immune responses to vaccination.

In a study by the University of Helsinki and HUS Helsinki University Hospital, the levels of antibodies associated with the SARS-CoV-2 virus were analysed in more than 1,200 employees in the social welfare and healthcare sector to determine whether there were differences in different antibody classes according to viral exposure. Dried saliva and blood samples collected between January and March 2021 were utilised in the study. The exposure and background data were collected using a questionnaire.

Based on the results, immunoglobulin G (IgG) has a 99.5% sensitivity and 75.3% specificity to distinguish people with two vaccinations from non-exposed and exposed individuals, individuals with previous Covid-19 infection, and those with one vaccination. IgG measured from saliva also had an 85.3% sensitivity and 65.7% specificity in distinguishing people with two vaccinations from the other groups.

The results of the study have been published in the Medical Microbiology and Immunology journal.

The study attested to the exposure of social welfare and healthcare employees to coronavirus, visible in the results as elevated antibody levels. A total of 47.5% of nurses and 47.7% of doctors were seropositive due to either a previous infection, vaccination or exposure, whereas only 8.7% of dentists had been exposed to the virus. In addition to dentists, the lowest antibody levels were observed in administrative staff and social workers.

The highest antibody levels in both the blood and saliva were found in those who had both had Covid-19 and had been vaccinated. The lowest antibody levels were seen in individuals who had not been exposed to the virus, who had not had a previous infection and who had not received a vaccination.

Against our expectations, there have been fewer coronavirus infections and instances of exposure among dental care staff compared to, for example, hospital doctors, even though a lot of aerosol-producing procedures are carried out close to the patient in dental care, researcher Laura Lahdentausta says.

At the time of sample collection, the dental care staff had also received the lowest number of coronavirus vaccines, which was reflected in their antibody levels.

Another goal of the study was to develop research methods. In fact, the study provides important information on the use of saliva in the determination of antibody levels.

Based on the results, dried samples reliably reveal antibodies associated with the virus, says Professor Pirkko Pussinen.

The benefit of dried saliva and fingertip blood samples is that they are easy to collect. Samples can be taken at home outside laboratory conditions. Their collection is inexpensive and, in the case of saliva samples, non-invasive.

In the future, this assay technique based on dried spot samples could be effectively utilised to monitor both the immune response produced by vaccination and the need for vaccines in large patient populations, Pussinen adds.

Original article: Lahdentausta L, Kivimki A, Oksanen L, Tallgren M, Oksanen S, Sanmark E, Salminen A, Geneid A, Sairanen M, Paju S, Saksela K, Pussinen P, Pietiinen M. Blood and saliva SARS-Cov-2 antibody levels in self-collected dried spot samples. Medical Microbiology and Immunology. Doi 10.1007/s00430-022-00740-x

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Blood and saliva SARS-Cov-2 antibody levels in self-collected dried spot samples

13-Jun-2022

Immunology

DE Shaw Research Licenses First-in-Class Therapeutic for Immunological Diseases to Lilly – PR Newswire UK

June 15, 2022 medical

NEW YORK, June 13, 2022 /PRNewswire/ -- D. E.Shaw Research (DESRES) today announced that it has entered into an exclusive global license agreement with Eli Lilly and Company (Lilly) for the clinical development and commercialization of DESRES's program of Kv1.3-targeted therapeutics for the treatment of various immunological and inflammatory diseases.

The lead compound, DES-7114, is an orally administered, highly selective small-molecule inhibitor of the ion channel protein Kv1.3. This first-in-class compound recently completed successful Phase 1 clinical trials in healthy volunteers and has demonstrated efficacy in preclinical models of several chronic inflammatory and autoimmune diseases, including ulcerative colitis, Crohn's disease and atopic dermatitis.

Under the terms of the agreement, Lilly will make an initial payment of $60 million to DESRES, with potential development and commercial milestone payments of up to $475 million, as well as royalties on worldwide sales.

The design of DES-7114 by DESRES was enabled by the use of proprietary special-purpose supercomputers that DESRES developed and constructed to perform ultra-high-speed, atomically detailed simulations of the three-dimensional motion of biologically and pharmaceutically significant molecules. A series of such simulations, in combination with experimental studies, resulted in DESRES's unique understanding of Kv1.3's structural, dynamic, and functional properties, leading to the design of compounds that bind strongly to the target protein while likely avoiding undesirable interactions with other ion channels.

"We're enthusiastic about DES-7114's potential, and are hopeful that it will ultimately have a meaningful impact on the lives of patients throughout the world," said DavidE.Shaw, Ph.D., chief scientist at DESRES. "We're also enthusiastic about teaming up with Lilly, which is one of the global leaders in therapeutics for immunological diseases, and is exceptionally well positioned to carry the compound forward through clinical development and commercialization."

"Kv1.3 inhibition represents a promising new approach in immunology," said AjayNirula, M.D., Ph.D., vice president of immunology at Lilly. "We are particularly excited about DESRES's discovery of DES-7114 because the molecule's properties could translate into significant advantages for addressing unmet patient needs."

About D. E. Shaw Research

D.E.Shaw Research (DESRES) uses advanced computational technologies to understand the behavior of biologically and pharmaceutically significant molecules at an atomic level of detail, and to design precisely targeted, highly selective drugs for the treatment of various diseases. Among its core technologies is a proprietary special-purpose supercomputer that it designed and constructed to perform molecular dynamics simulations more than 100 times faster than the world's fastest general-purpose supercomputers. DESRES uses these machines, together with machine learning methods and other computational techniques, in both internal and collaborative drug discovery programs. For more information, visit http://www.DEShawResearch.com.

ContactMadeleine WeingartenD. E. Shaw ResearchMadeleine.Weingarten@DEShawResearch.com

Logo - https://mma.prnewswire.com/media/1837394/DESRES_Logo.jpg

SOURCE D. E. Shaw Research

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DE Shaw Research Licenses First-in-Class Therapeutic for Immunological Diseases to Lilly - PR Newswire UK

Immunology

A New Era: Creating Defenses Against Disease After COVID-19 – The University of Arizona Health Sciences |

June 15, 2022 medical

As the vortex of the COVID-19 pandemic consumed the world in 2020, scientists worked at a frantic pace to understand the new virus sweeping the globe. The discoveries surrounding SARS-CoV-2 were impressive not only for the speed in which they took place, but also for the new pathways of research they opened.

To the average person, it looked as though scientists were making daily breakthroughs as spike proteins, antibodies and messenger RNA vaccines became topics of everyday conversation. But revolutionary discoveries are rarely Eureka! moments. Instead, scientific advances are almost always the culmination of research that occurs outside of the spotlight. In the realm of immunology, decades of research on the immune system, the human genome and a multitude of other viruses laid the foundation to quickly unravel the mysteries of SARS-CoV-2 and COVID-19.

The immediate end goal was met when COVID-19 vaccines and treatments became available. But the impact of that research is far from over, according to Deepta Bhattacharya, PhD, keynote speaker at the inaugural University of Arizona Health Sciences Tomorrow is Here Lecture Series. He believes the lessons learned during the COVID-19 pandemic have the potential to change the future of science.

The pandemic has shown us that the tools are out there to make infectious disease far less burdensome, not only in the U.S., but globally, said Dr. Bhattacharya, professor of immunobiology in the UArizona College of Medicine Tucson and BIO5 Institute member. We've shown what our technology can do and what our responses can be, and I don't see any reason to accept the status quo anymore.

One of the pandemics biggest lessons, Dr. Bhattacharya said, is that the basics matter.

When people say the COVID-19 vaccines were developed in record time, they really weren't, Dr. Bhattacharya said. They were built on the backs of decades of research that allowed us to move quickly.

Three decades before an unknown virus surfaced in Wuhan, China, scientists were undertaking a massive endeavor known as the Human Genome Project. The intent was to sequence and map all of the genes 3 billion in total that make up the human genome.

In the beginning, the available technology was unreliable and slow, preventing researchers from sequencing more than a few hundred genes at a time. As technology improved, sequencing rates increased dramatically, and in April 2003, the Human Genome Project succeeded in reading the complete genetic blueprint of a human being.

We've shown what our technology can do and what our responses can be, and I don't see any reason to accept the status quo anymore.Deepta Bhattacharya, PhD

The Human Genome Project was criticized by people who asked, What are we really learning from this? What diseases have been cured by understanding and knowing the human genome sequence? Dr. Bhattacharya said. But it's important not to just focus on immediately translatable outcomes. Think about all of the outcomes that came as a result of that project, some of which undoubtedly were the sequencing technologies.

The same sequencing technologies that unraveled the mysteries of the human genome could be applied to viruses. Fast forward to January 2020, and within weeks of being confronted by an unknown pathogen, scientists sequenced and identified the novel coronavirus they dubbed SARS-CoV-2.

Some of the technologies people criticized for not necessarily having an immediate translational impact, now very obviously did, Dr. Bhattacharya said.

The Human Genome Project started in 1990, but the research that laid the foundation for the COVID-19 vaccines has an even longer history. As early as the mid-1970s, immunologists were studying common coronaviruses that affected other species, including mouse hepatitis virus.

It was, in some ways, thankless work. The researchers were asked, why are you studying this? This is a mouse coronavirus why do you care what disease it causes? Dr. Bhattacharya said. What the pandemic has shown us is that those studies taught us an awful lot in terms of preparedness. From these studies, it turned out that the immune response needed to be aimed at a particular protein that the virus makes called spike.

Identifying the viruss Achilles heel wasnt enough, though. Researchers needed to find a way to engineer the spike protein to create an immune response against the virus. That work happened at the National Institutes of Healths Vaccine Research Center. There, scientists were studying respiratory syncytial virus, which causes severe respiratory infections in children, and another common coronavirus that causes cold-like symptoms.

Once engineered, the spike protein needed to be safely delivered to the cells nucleus without killing the cell. Again, the answer came from research that was decades in the making in this case, messenger RNA (mRNA) research at the University of Pennsylvania.

All of that early work that sort of circuitous path science sometimes takes led us to figure out the perfect solution to generate vaccines and immune responses to emerging pathogens, said Dr. Bhattacharya.

On the scientific front, one of the biggest applications from the pandemic can be found in the immunology that led to the development of the highly effective COVID-19 vaccines.

I think structure-based vaccinology is the wave of the future, said Dr. Bhattacharya, whose primary research focuses on a family of viruses known as flaviviruses, which cause diseases including dengue, Zika, Japanese encephalitis, yellow fever and West Nile. The pandemic really showed the power of that particular approach to actually control the immune system and what it's aimed at. Some of the technologies that came from COVID-19 can absolutely be applied to the flaviviruses, as well.

Dr. Bhattacharya, who hopes to develop an effective vaccine for flaviviruses, says none of the flaviviruses have come close to causing the worldwide destruction perpetuated by SARS-CoV-2, though scientists were surprised by the spread of the Zika virus, which reached epidemic status in Brazil in 2016. Still, no one knows which virus could be the source of the next pandemic.

We don't really know what's going to come next, so that means studying families of not just viruses, but also bacteria and fungi, and building up that broad knowledge base and technology that allows us to move quickly, he said. Prevention and preparedness are worth many tons of cure for infectious diseases.

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A New Era: Creating Defenses Against Disease After COVID-19 - The University of Arizona Health Sciences |

Immunology

3 summers of COVID and now monkeypox – you have questions, Vaneet has answers – WUKY

June 15, 2022 medical

From UK Now:

Monkeypox has exploded into the news recently, with the Centers for Disease Control and Prevention (CDC) closely tracking cases that have been recently reported in several countries that dont normally have monkeypox activity, including the U.S.

University of Kentucky immunology and virology expert Ilhem Messaoudi, Ph.D., answered our questions about the monkeypox virus. Messaoudi, chair of the College of Medicines Department of Microbiology, Immunology, and Molecular Genetics, shares what you need to know about monkeypox including symptoms, risk and treatment.

Q: What is monkeypox?

A: Monkeypox is a disease caused by the monkeypox virus, which is a member of the orthopoxvirus genus within the Poxviridae family. It is in the same genus as variola virus, which causes smallpox.

Is Monkeypox the next COVID? No. Unlike SARS-CoV-2, monkeypox is contagious once the person has developed symptoms, and it is not easily transmitted between individuals. Vaccines against smallpox/monkeypox are available. We also have access to therapeutics in the form of antiviral and vaccinia immune globulins.

Q: What are the symptoms of monkeypox?

A: The incubation period is often seven to 14 days but can be as long as 21 days. Symptoms first start with chills, fever, aches and swollen lymph nodes. This is followed by the appearance of a rash that progresses to blisters.

Q: How does monkeypox spread?

A: Monkeypox is spread via close prolonged contact with body fluids/lesion materials, for example, by caring for or interacting closely with someone exhibiting symptoms, getting bit by an infected animal or manipulating sick animals, or handling contaminated materials. It can be spread via the respiratory route, mucosal route or through broken skin.

Q: As of now, how would you assess the risk for Kentuckians?

A: The risk for Kentuckians is pretty low. However, please note that there is a suspected case in Virginia. Given global travel and increased activities now that several COVID-19 restrictions have been lifted, and the potential of large gatherings at upcoming events, everyone should be vigilant.

Q: How can one best prevent or avoid monkeypox?

A: Practice good hand hygiene, which we should all be very good at by now. If you find yourself in an area where monkeypox has been detected, avoid contact with animals that are sick or found dead. For health care workers caring for monkeypox patients, PPE including respiratory protection and patient isolation are needed.

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3 summers of COVID and now monkeypox - you have questions, Vaneet has answers - WUKY

Immunology

Antibodies in breast milk help shape infants’ gut bacteria and immunity | Cornell Chronicle – Cornell Chronicle

June 15, 2022 medical

Researchers have known for some time that maternal breast milk provides critical nutrients for newborns, and antibodies from mothers vaccinated against a specific disease-causing bacterium or virus can be transferred via breast milk to babies. Now a new preclinical study by Weill Cornell Medicine investigators shows that one specific set of antibodies that is induced naturally by gut beneficial bacteria can be transferred from mothers to infants through breast milk and help infants defend against infection-induced diarrheal illness.

The study suggests boosting these naturally-produced antibodies in mothers might enhance infants immunity against bacterial pathogens that cause infectious gastrointestinal diseases.

In the study, published June 10 in Science Immunology, the team focused on a class of antibodies called IgG, which help rid the body of infectious bacteria and viruses.Little was known about how IgG antibodies that are naturally induced by gut bacteria influence infant gut immunity. So the investigators used a mouse model to determine how these IgG antibodies are transferred from a mothers blood to her breast milk and how they protect young mice from Citrobacter rodentium (equivalent to pathogenic E. coli in humans) that causes potentially dangerous intestinal infections.

We found that these IgG antibodies were protective against gut infection in the babies and that we could enhance this protection, said senior author Melody Zeng, an assistant professor of immunology in pediatrics within the Department of Pediatrics and a member of the Gale and Ira Drukier Institute for Childrens Research at Weill Cornell Medicine.

Just as antibodies against the SARS-CoV-2 virus are detected in the breast milk of women who had been vaccinated with mRNA vaccines for COVID-19, the researchers sought to confer extra protection against intestinal infections in infants by inducing IgG antibodies that could be transferred this way. They developed a vaccine using a component found in gut bacteria, then immunized female mice with it before they became pregnant.

The same concept, in which vaccination enhances mothers IgG antibody levels and transfers this immunity to her babies, could protect human babies, Zeng said. This strategy could especially benefit premature babies, since they tend to be at much higher risk from diarrheal diseases.

Such infections pose significant dangers for young children in general. Diarrheal illnesses are the second leading cause of death among children under five, according to the World Health Organization.

In their experiments, the researchers, including co-first authors Katherine Sanidad and Mohammed Amir, both postdoctoral associates in the Zeng lab, first demonstrated that when passed to infant mice through breast milk, IgG prevented disease-causing bacteria from attaching themselves to the lining of infants intestines, an early step in infection.

They also studied how IgG interacted with another set of microbes beneficial bacteria that live in the gut to facilitate healthy development of gut bacteria in infants. Scientists are finding that these microbes contribute to the development and function of the immune system. For instance, helpful bacteria train the immune system to recognize their pathogenic relatives.

This study uncovered long-term effects of these protective IgG antibodies too. Mice that never received IgG from their mothers developed abnormal microbial communities within their guts, which led to changes to their immune systems. Specifically, the researchers found an increase in gut immune cells that produce IL-17, a proinflammatory cytokine that is linked to inflammatory diseases. As adults, the IgG-deprived mice were more susceptible to abnormal inflammation associated with inflammatory bowel disorder.

Our findings really underscore the benefits of breastfeeding, both immediately and for the long-term development of the immune system in the offspring, Zeng said.

Melody Zeng is a consultant for Guidepoint.

Wynne Parry is a freelance writer for Weill Cornell Medicine.

Immunology

OSE Immunotherapeutics Appoints its International Scientific Advisory Board – StreetInsider.com

June 15, 2022 medical

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NANTES, France, June 09, 2022 (GLOBE NEWSWIRE) -- OSE Immunotherapeutics SA (ISIN: FR0012127173; Mnemo: OSE) today announces the appointment of six leading international experts to its newly formed Scientific Advisory Board (SAB) to guide the Company in its next phases of growth and scientific orientations.

We are proud to have gathered this team of independent world-renowned key-opinion leaders in immunology, immuno-oncology and inflammation, commented Nicolas Poirier, Chief Scientific Officer of OSE Immunotherapeutics. Since OSEs inception, it has been an incredible journey at the forefront of immunology for translating our scientific discoveries into first-in-class innovative immunotherapy treatments against cancers, autoimmune or inflammatory diseases. We will now benefit from their outstanding and highly complementary expertise to further develop our R&D capabilities and nurture the science developed by OSE.

Dominique Costantini, Chief Executive Officer of OSE Immunotherapeutics, adds: We are very pleased and honored to bring together experts with such scientific high level and strategic insight in immunology to guide the Company in its scientific orientations. Together with the OSE team, this Board will help addressing novel issues and challenges pertaining to our current and future research to prepare the Companys new phase of growth focused on bringing new entities into our portfolio and advancing our preclinical and diversified first-in-class products in immuno-oncology and immunology & inflammation.

The SAB, chaired by Pr. Wolf-Herv Fridman who will lead the Board's reflections and discussions, will comprise the followings:

Prof. Wolf-Herv Fridman, MD, ChairmanProfessor Emeritus of Immunology at the Universit de Paris Medical School in Paris, FranceDr. Fridmans research focused on the analysis of the tumor microenvironment. Since 2005, his studies have changed the paradigm of host/cancer interactions by demonstrating that the immune contexture, taking into account the functionality, the location and the density of the immune infiltrate in colorectal tumors, is the major prognostic factor for human cancers. He is involved in the development of bioinformatic tools to quantify cells of the tumor microenvironment which are being successfully applied to predict prognosis and immunotherapeutic responses in Renal Cell Cancers, Colorectal Cancers or Sarcomas. One major achievement is the establishment of an immune classification of soft tissue sarcoma tumors that allowed to demonstrate that Tertiary Lymphoid Structures (TLS) and B cell signatures, better than T cells, predicted favorable clinical outcome and therapeutic response to anti-PD- 1 therapy in patients. These findings were recently extended to other cancers treated with immune check-point blockers showing that plasma cells generated inside TLS produce anti-tumor antibodies associated with patients response to immunotherapy. They open the way for novel immune-based tools for efficient prognosis and therapy of cancers.

Dr. Sophie BrouardImmunologist and Doctor in veterinary sciences, Director of Research at the Institut National de la Sant et Recherche Mdicale (INSERM, National Institute for Health and Medical Research) in Nantes, France Dr. Sophie Brouard is Director of Research in the INSERM unit located in Nantes (France) and is working in immunology (auto-immune diseases and transplantation). She is an immunologist interested in fundamental and translational questions on the process of inflammation, chronicity, rejection and tolerance. Previously, she served as Director of the Centaure national RTRS (Rseau Thmatique de Recherche et de Soins) transplantation network in France. Dr. Brouard received the Bronze medal from the French National Center for Scientific Research (CNRS) in 2004, the price from Medicine Academy in 2012, the medal of innovation of the CNRS in 2020 and the Trophe of Academy-Biotech partnership from the Nantes University in 2021. She funded three companies, TclandExpression, Effimune and BioMadvanced.

Dr. Brouard participates and is co-authors of 11 patents. She published around 200 scientific papers (h-factor = 43).

Bernard Malissen, PhDGroup Leader at Centre dImmunologie de Marseille-Luminy and Founding-Director of Center for Immunophenomics, Marseille, FranceDr. Bernard Malissen pioneered the use of gene transfer approaches to dissect the function of Major Histocompatibility Complex (MHC) molecules. He also succeeded reconstructing a full T cell antigen receptor (TCR) complex and demonstrated that the present-day signaling subunits associated with antigen receptors stem from a common primordial building block. He provided the first evidence for chromosomal inversion during TCR gene rearrangements.

His team was also the first to elucidate the atomic structure of an alloreactive TCR in complex with its peptide-MHC ligand, providing a molecular explanation for the basis of transplant rejection and TCR binding-degeneracy. His recent interests extend to dendritic cells and macrophages, leading him to disentangle their functional complexity primarily in the skin. To make sense of the complexity of the signal transduction networks involved in T cell activation, he recently used omic approaches to provide a systems level picture of the TCR signal transduction network and of its tuning by costimulatory and coinhibitory receptors.

Bernard Malissen published 400 scientific papers, (h-factor of 94) and ranked for the last 5 years among the most highly cited researchers in Immunology.

Dr. Myriam Merad, MD, PhDDirector of the Precision Immunology Institute at Mount Sinai School of Medicine in New York and the Director of the Mount Sinai Human Immune Monitoring Center (HIMC), USDr. Merad is an internationally acclaimed physician-scientist and a leader in the fields of dendritic cell and macrophage biology with a focus on their contribution to human diseases. Dr. Merad identified the tissue resident macrophage lineage and revealed its distinct role in organ physiology and pathophysiology. She established the contribution of this macrophage lineage to cancer progression and inflammatory diseases and is now working on the development of novel macrophage-targeted therapies for these conditions. In addition to her work on macrophages, Dr. Merad is known for her work on dendritic cells, a group of cells that control adaptive immunity. She identified a new subset of dendritic cells, which is now considered a key target of antiviral and antitumor immunity.

Dr. Merad leads the Precision Immunology Institute at the Icahn School of Medicine (PrIISM) to bring immunology discoveries to the clinic. PrIISM integrates immunological research programs with synergistic expertise in biology, medicine, technology, physics, mathematics and computational biology to enhance our understanding of human immunology. She also founded the Human Immune Monitoring Center at Mount Sinai, one of the worlds most sophisticated research centers, which uses cutting-edge single-cell technology to understand the contribution of immune cells to major human diseases or treatment responses.

Dr. Merad has authored more than 200 primary papers and reviews in high profile journals. Her work has been cited several thousand times. She receives generous funding from the National Institutes of Health (NIH) for her research on innate immunity and their contribution to human disease, and belongs to several NIH consortia. She is an elected member of the American Society of Clinical Investigation and the recipient of the William B. Coley Award for Distinguished Research in Basic and Tumor Immunology.She is the President-elect of the International Union of Immunological Societies (IUIS). In 2020, she was elected to the National Academy of Sciences in recognition of her contributions to the field of immunology.

Prof. Charles N. Serhan, PhD, DScPr. Serhan is the Simon Gelman Professor of Anaesthesia (Biochemistry and Molecular Pharmacology) at Harvard Medical School, Professor of Oral Medicine, Infection and Immunity at Harvard School of Dental Medicine, USHe is Director of the Center for Experimental Therapeutics and Reperfusion Injury at Brigham and Womens Hospital and Co-Director of the Brigham Research Institute. Charles received a Bachelor of Science in biochemistry from Stony Brook University followed by a Doctorate in experimental pathology and medical sciences from New York University School of Medicine. He was a visiting scientist and postdoctoral fellow at the Karolinska Institutet, Stockholm with Professor Bengt Samuelsson (Nobel Laurate Medicine 82). In 1987, he joined the faculty at Harvard Medical School and in 1996 received the honorary degree from Harvard University.

Pr. Serhan has experience leading multidisciplinary research teams as PI/PD for several NIH supported Program Project Grants and a P-50 Center Grant. He is currently Program Director of the Program Project entitled Resolution Mechanisms in Acute Inflammation: Resolution Pharmacology (P01-GM095467).

He received several research awards including an NIH MERIT and recent international awards: 2016 Ross Prize in Molecular Medicine, International Eicosanoid Research Foundations 2017 Lifetime Achievement Award, the American Society of Investigative Pathology 2018 Rous Whipple Award, the 2018 British Pharmacology Societys Gaddum International Prize and Award Lecture, and the2019 Honorary Lifetime Award, Society for Leukocyte Biology, for excellence in leukocyte biology research.

His h-index is 172 in google scholar.

Dr. Jennifer Wargo,M.D., M.M.Sc.Professor of Genomic Medicine & Surgical Oncology, UT MD Anderson Cancer Center, HoustonAfter completing her medical degree, she entered surgical residency training at the Massachusetts General Hospital/Harvard Medical School where she became interested in the biology and treatment of cancer. During her training, she completed 2 fellowships in surgical oncology with a focus on immunotherapy for cancer.

Dr. Wargo was recruited to the Division of Surgical Oncology at Massachusetts General Hospital in July 2008 and had an active research laboratory focusing on melanoma tumorigenesis and immunotherapy for cancer. One exciting finding involved data describing the effect of BRAF-targeted therapy on tumor antigen expression in melanoma as a basis for combining targeted therapy and immunotherapy in the treatment of this disease. Dr. Wargo validated those findings in patients treated with BRAF inhibitors. She has continued critical studies to better understand the effects of BRAF inhibition on immune responses in melanoma and established a unique set of serial tumor biopsies and blood samples from patients enrolled in clinical trials on BRAF inhibitors. Through analysis of these samples, she contributed significantly to the world literature regarding resistance mechanisms and the effect of targeted therapy on anti-tumor immunity.

Dr. Wargo was recruited to MD Anderson Cancer Center in September 2013 to continue this work and to build a program to collect serial biopsies in patients with melanoma and other cancers on targeted therapy and immunotherapy, and to better understand responses to therapy and to develop novel strategies to combat resistance.

ABOUT OSE ImmunotherapeuticsOSE Immunotherapeutics is an integrated biotechnology company focused on developing and partnering therapies to control the immune system for Immuno-Oncology and Immuno-Inflammation. Its balanced first-in-class clinical and preclinical portfolio has a diversified risk profile:

Immuno-Oncology first-in-class products

Immuno-Inflammation first-in-class products

CoVepiT: a prophylactic second-generation vaccine activating cytotoxic T lymphocytes against COVID-19, developed using optimized epitopes from SARS-CoV2 viral proteins, epitopes non impacted by multi-variants. Shows good tolerance and very good level of T cell immune response. In clinical testing, a long-term memory response was confirmed at 6 months.

Click and follow us on Twitter and LinkedInhttps://twitter.com/OSEIMMUNOhttps://www.linkedin.com/company/10929673

Contacts

Forward-looking statementsThis press release contains express or implied information and statements that might be deemed forward-looking information and statements in respect of OSE Immunotherapeutics. They do not constitute historical facts. These information and statements include financial projections that are based upon certain assumptions and assessments made by OSE Immunotherapeutics management in light of its experience and its perception of historical trends, current economic and industry conditions, expected future developments and other factors they believe to be appropriate.

These forward-looking statements include statements typically using conditional and containing verbs such as expect, anticipate, believe, target, plan, or estimate, their declensions and conjugations and words of similar import. Although the OSE Immunotherapeutics management believes that the forward-looking statements and information are reasonable, the OSE Immunotherapeutics shareholders and other investors are cautioned that the completion of such expectations is by nature subject to various risks, known or not, and uncertainties which are difficult to predict and generally beyond the control of OSE Immunotherapeutics. These risks could cause actual results and developments to differ materially from those expressed in or implied or projected by the forward-looking statements. These risks include those discussed or identified in the public filings made by OSE Immunotherapeutics with the AMF. Such forward-looking statements are not guarantees of future performance. This press release includes only summary information and should be read with the OSE Immunotherapeutics Universal Registration Document filed with the AMF on 15 April 2022, including the annual financial report for the fiscal year 2021, available on the OSE Immunotherapeutics website. Other than as required by applicable law, OSE Immunotherapeutics issues this press release at the date hereof and does not undertake any obligation to update or revise the forward-looking information or statements.

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OSE Immunotherapeutics Appoints its International Scientific Advisory Board - StreetInsider.com

Immunology

22pc of people tested for Covid-19 are positive as a ‘return to normal’ sees cases rise – Independent.ie

June 15, 2022 medical

Twenty-two percent of people tested for Covid-19 are positive as cases are rising, an immunology expert has said.

rofessor of Experimental Immunology at Trinity College Dublin Kingston Mills, said the fact that people are back to normal has contributed to a rise in cases.

"The number of cases has risen here, but its not just in Ireland.In the UK, Portugal and Germany, there has been a risein the past couple of weeks, he said on RT Radio 1s This Week.

"This is really on the back of the variants BA.4, BA.5, theseare sub-variants of Omicron, which are distinct from the original Omicron, they have mutated further. They are moretransmissible.

Mr Mills also pointed to the fact that people are now back to normal, and there's no social distancing, no mask-wearing.

There is a lot of contact,a lot of hospitality, so all of that is contributing to the rising case numbers.

He pointed out that the numbers in hospital are rising, so that does suggest that the case numbers are rising.

As of 8am, there were 397 people in hospital with Covid-19, this is an increase of 37 from yesterdays statistics.

The positivity rate of those that are tested has gone up from16 to 22pc, ProfMills said.

"So 22pc of all people that are tested are turning out to be positive, andthats an indication that we are getting an increase in the number of cases, as well as the number ofhospitalisations.

Omicron and its sub-variants largely infect theupper respiratory tract and they dont go as much into the lung, unless somebody has an underlying lung condition.

Prof Mills said that for a normal, healthy person this is not a very serious disease, but for people who are older, or people with underlying medical conditions or on some immunotherapy that might make their immune system suppressed, it is still a concern.

And these are the ones that are vulnerable now. It's important that if they havent been vaccinated with a fourth dose, or have recently had Covid, they should get a booster vaccine."

Prof Mills saidhe knew of a lot of older people, and people with underlying health conditions who havent yet had Covid who are still worried about getting it, because they feel that they may end up in hospital if they do get it and that is a big concern.

"And that is the big worry in this with increasing case numbers, it isinevitable that some will end up in hospital.

For the normal healthy person, its not a big deal getting this infection, in fact getting the infection now, especially if youve had the vaccine, three doses of the vaccine, will add to your immunity and probably prevent you from getting re-infected at this stage.

But the trouble is, even getting infected with the original Omicron is not now having as much protection against reinfection with B.A4 and B.A5 and thats the worry about this virus, it keeps changing and if it changes again, that will make it even more difficult for the vaccines to work.But the good news is the vaccines do prevent severe disease."

Prof Mills said those who have had their vaccine doses are in a better place than those who have not been vaccinated.

There is a lot of concern for those who are not vaccinated in the older age group or with underlying medical conditions, he said.

The rest is here:
22pc of people tested for Covid-19 are positive as a 'return to normal' sees cases rise - Independent.ie