StemCell Therapy

The Trump administration doubled its orders from Pfizer and Moderna this month to 200 million doses each. But both vaccines are given as two doses per person, meaning the U.S. supply will only cover 200 million of the nation's 250 million adults. Authorizing more vaccines for emergency use could immediately increase that stockpile, and also help ensure sufficient vaccine when inoculation is allowed for teens and children.

Johnson & Johnson is preparing to release the first efficacy data on its shot, which is given as a single dose, in January. AstraZeneca could also release more data as early as next month from its late-stage trials, officials with the federal government's Operation Warp Speed said recently. (The company said in a statement that it has "no further updates on the US specific trial.")

An early frontrunner in the global vaccine race, AstraZeneca has sold more shots worldwide than any other manufacturer. Between agreements with the World Health Organization, the Coalition for Epidemic Preparedness and Innovation and the Serum Institute, a mass manufacturer in India, the British drugmaker has promised nearly 1 billion shots to other countries not including the 300 million it pledged to the U.S.

AstraZenecas vaccine is vastly cheaper than others and much easier to ship and store than vaccines such as Pfizers, that require ultra-cold freezers or dry ice. That makes it an appealing option for hard-to-reach areas in the U.S., as well as lower-income countries with less advanced infrastructure.

But the outlook for the company's vaccine is hazy after AstraZeneca reported last month that nearly 3,000 trial volunteers in the U.K. were accidentally given a half-strength first dose. The regimen proved 90 percent effective in early data, beating the 62 percent efficacy of two standard doses. Some vaccine experts think the lower dose's success could be a statistical fluke, since 3,000 people is a small slice of the tens of thousands of people enrolled in the company's trials; others say it could indicate a clearly better option.

AstraZeneca would still have to fully test the lower dosing regimen before applying to the Food and Drug Administration for emergency-use authorization. The agency is also requiring that drug companies follow at least half the trial volunteers for two months after their last dose.

A company spokesperson said that there is "nothing to share on U.S. filing plans at this time."

But the FDA's minimum criteria for seeking authorization do not tell the full story of a vaccine's value, said Peter Hotez, a virologist and dean of the National School of Tropical Medicine at the Baylor College of Medicine.

Initial efficacy over the first two months is only one of several aspects that requires consideration," said Hotez, who is also developing a potential coronavirus shot with partners in India. Other vaccines may offer advantages in terms of durability of protection, tolerability, safety, suitability for children or adolescents, and for that well require additional vaccines.

Pfizer and Moderna only recently started studying their vaccines in children as young as 12 years old, and no manufacturer has begun trials in children even younger. Regulators have also called for more data in pregnant women and for certain risk factors like heart disease, diabetes and other illnesses that could affect the immune system. Health experts say that a vaccine that may only work moderately overall may be best for key subpopulations, such as pregnant women.

The latest news in health care politics and policy.

And some of the vaccines still in development may prove easier to manufacture, transport or administer than the Pfizer and Moderna shots.

Both of those authorized vaccines use relatively new messenger RNA technology to instruct cells to make a protein found on the virus, which revs up the body's immune system. J&J and AstraZeneca use a more traditional method, in which small bits of DNA from the coronavirus are edited into a weakened version of another virus called an an adenovirus. When the adenovirus enters cells, they read its DNA and produce a protein found in the coronavirus.

One theory about the AstraZeneca dosing confusion is that a full dose of the adenovirus triggered too big of an immune response so the body didnt have time to learn much about the coronavirus it was meant to protect against, said Rasmussen. There is still value in having that information, because maybe [AstraZeneca] can start assessing that half-dose regimen.

But the AstraZeneca data could present a quandary for FDAs independent vaccine advisory panel, which has been meeting publicly to discuss each candidate in a bid to boost transparency and public confidence. The company has said that combined results so far from its Phase III trials show its vaccine to be 70 percent effective. But the two dosing regimens tell different stories: 90 percent is basically comparable with the existing vaccines; 62 percent is not.

You cant reasonably combine data from two different dosing strategies, two different dosing intervals and two different placebo groups, Paul Offit, a vaccine expert at the University of Pennsylvania who sits on the FDAs expert panel, the Vaccines and Related Biological Products Advisory Committee.

It also presents a sticky situation for the largest national vaccination plan in history. While the two vaccines authorized now have nearly identical efficacy and safety profiles and use the same technology, having a more varied roster of vaccines would be harder to distribute fairly.

There are obvious ethical issues: If one vaccine is more effective than the others, who gets what, right? said Philip Landrigan, director of the global public health program at Boston College, who stressed the importance of clear federal planning if that happens. Transparency and openness have another benefit beyond just ensuring that the system works well it could persuade people who are reluctant to get the vaccine.

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The first Covid vaccines were triumphs. What if the next are only OK? - POLITICO

Researchers found that during pregnancy, the female sex hormones instruct the thymus to produce Tregs specialised in dealing with physiological changes during pregnancy.

How the immune system adapts to pregnancies has puzzled scientists for decades. Now, findings from an international group of researchers, led by experts at Karolinska Institutet in Sweden, reveal important changes that occur in the thymus to prevent miscarriages and gestational diabetes. The study was published today (23 December 2020) in Nature.

The thymus is a central organ of the immune system where specialised immune cells called T lymphocytes mature. These cells, commonly referred to as T cells, then migrate into the blood stream and tissues to help combat pathogens and cancer. An important T cell subset, known as a regulatory T cell or Treg, is also produced in the thymus. The main function of a Treg is to help regulate other immune cells.

Researchers found that during pregnancy, the female sex hormones instruct the thymus to produce Tregs specialised in dealing with physiological changes during pregnancy. The studywhich involved researchers at Karolinska Institutet, the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA) in Vienna, University of British Columbia in Vancouver, further reveals that RANK, a receptor expressed in the thymus epithelia, is the key molecule behind this mechanism.

The study builds on work by a team at the University of Birmingham as researcher and collaboratorProfessor Graham Andersonfrom the Institute of Immunology and Immunotherapy explains: In 2007, our lab provided the first evidence that RANK plays a critical role in controlling thymus function in the steady state immune system. Now, this new research shows how RANK in the thymus regulates the immune system in pregnancy, which is an exciting new direction.

We knew RANK was expressed in the thymus, but its role in pregnancy was unknown, says first and co-corresponding author Dr. Magdalena Paolino, assistant professor at the Department of Medicine, Solna, Karolinska Institutet.

To get a better understanding, the authors studied mice where RANK had been deleted from the thymus.

The absence of RANK prevented the production of Tregs in the thymus during pregnancy. This resulted in less Tregs in the placentas, leading to miscarriages, continues Magdalena Paolino.

This latest study further shows that in normal pregnancies, the produced Tregs also migrate to the mothers fat tissue to prevent inflammation and help control glucose levels in the body. Pregnant mice lacking RANK had high levels of glucose and insulin in their blood and many other indicators of gestational diabetes, including fetal macrosomia.

Similar to babies of women with gestational diabetes, the newborn pups were much heavier than average, explains Magdalena Paolino.

In addition, the deficiency of Tregs during pregnancy was proven to result in long-lasting transgenerational effects on the offspring, which remained prone to diabetes and overweight throughout their life spans. Giving the RANK deficient mice thymus-derived Tregs that had been isolated from normal pregnancies, reversed all issues including fetal loss and maternal glucose levels and the body weights of the pups.

The researchers also analysed women with gestational diabetes, revealing a reduced number of Tregs in their placentas, much similar to the study on mice.

This research changes our view of the thymus, as an active and dynamic organ required to safeguard pregnancies, Magdalena Paolino says. It also provides new molecular insight for gestational diabetes, a disease that affects many women and which we still know little about. It emphasises the importance of clinics detecting and managing glucose metabolism in pregnant women to avert its long-term effects.

Co-corresponding author Dr. Josef Penninger notes that how rewiring of the thymus contributes to a healthy pregnancy was one of the remaining mysteries of immunology until now.

Our work over many years has now not only solved this puzzle pregnancy hormones rewire the thymus via RANK but uncovered a new paradigmatic function: the thymus not only changes the immune system of the mother to allow the fetus, but it also controls metabolic health of the mother, Josef Penninger says.

The study was possible thanks to a close collaboration between the laboratory of Magdalena Paolino at Karolinska Institutet and the laboratories of Josef Penninger at IMBA and UBC. Researchers from the CeMM Institute and the Medical University of Vienna, as well as from the Universities of Birmingham and Oxford also participated.

For more information please contactMagdalena Paolino, Assistant Professor,Department of Medicine Solna, Karolinska Institutet.

Full paper:RANK links thymic Tregs to fetal loss and gestational diabetes in pregnancy, Magdalena Paolino*, Rubina Koglgruber, Shane J. F. Cronin, Iris Uribesalgo, Esther Rauscher, Juergen Harreiter, Michael Schuster, Dagmar Bancher-Todesca, Blanka Pranjic, Maria Novatchkova, Andrea White, Verena Sigl, Sabine Dekan, Juan P. Fededa, Thomas Penz, Christoph Bock, Lukas Kenner, Georg A. Hollnder, Graham Anderson, Alexandra Kautzky-Willer, and Josef M. Penninger*, Nature, in press 23/12/2020

DOI:10.1038/s41586-020-03071-0.

Grant information:

The researchers were supported by grants from Karolinska Institutet, the Ragnar Soderberg Foundation, the Swedish Research Council, the Swiss National Foundation, The Wellcome Trust, MRC, CRUK, Austrian Science Fund, European Training Network, IMBA, a Canada150 Chair, the T. von Zastrow foundation and the European Research Council.

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New research highlights the importance of the thymus in successful pregnancies - University of Birmingham

With a coronavirus vaccine right around the corner, it feels like we are almost out of the woods. Don't get ahead of yourselfaccording to the BBC, healthy Americans under the age of 65 won't start getting the vaccine at least until April, with the inoculation efforts stretching throughout 2021. We still have months ahead of us and still have plenty of time to contract COVID-19 if we let our guard down, which is why it's important to find ways to combat the viruslike this one drink to weaken COVID.

If you happen to contract a milder form of the illness, you have some light treatment options at your disposal. According to Johns Hopkins, drinking fluids and taking over the counter medicine to reduce the fever can help get you feeling better, but if you want an extra holistic boost that can help reduce the symptoms of COVID, look no further than a daily glass of pumpkin seed milk.

Here's why, and for more tips during COVID, here's The One Vitamin Doctors Are Urging Everyone to Take Right Now.

"Your immune system right now is very busy filtering your cells to know which are the safe ones and which do not belong to your body," says Jason Hughes, RD and head coach of Vegan Liftz. "Thus, it needs a daily dose of vitamins and minerals from the foods you eat and the beverages you drink, to keep you active."

"[One] drink to weaken the symptoms of viruses such as COVID-19, and to strengthen your immune system, is Pumpkin Seed Milk," Hughes continued. "This drink consists of fresh and natural ingredients, which makes it very healthy, and at the same time, delicious. Pumpkin seed milk boosts your immune system, making it a lot stronger to fight viruses and infections. Pumpkin seed is a great source of zinc, and other vitamins and minerals, which are the nutrients you need to prevent COVID-19."

According to Healthline, pumpkin seed milk has officially been studied in U.S. clinical trials exploring zinc's effect on reducing coronavirus symptomsand has been proven to reduce inflammation and improve one's immune system. Even if you don't have COVID-19 symptoms, the drink helps promote bone, urinary, and prostate health among several other factors, making it an exciting, healthy drink to keep an eye on.

If you test positive for COVID-19, follow the advice of the Harvard School of Health and self-isolate as soon as you can and avoid contact with other family members or roommates. If you begin having trouble breathing or feel like you run out of breath easily, visit the emergency room as soon as possible.

If you have mild symptoms, a glass of pumpkin seed milk might have you back on your feet sooner than expected. Even when you start feeling better, incorporating a glass of this hot, new beverage might be just the thing you need to stay healthy.

For more healthy tips, be sure to sign up for our newsletter.

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Drinking This One Thing Every Day May Help Weaken COVID-19 - Eat This, Not That

Bharat Biotechs indigenous vaccine Covaxin induced immunity against covid-19 through antibodies as well as T-cells and was found to be safe with no serious adverse events during its first two stages of trial, a pre-print of the phase 2 study showed.

It is hypothesised that the humoral and cell-mediated responses reported in this study may persist until at least 6-12 months after the second vaccination dose," showed the trial report, which is yet to be peer-reviewed.

Also Read | Inside the farmer disquiet at Delhis doorstep

Humoral immune responses are caused by antibodies, while cell-mediated responses are caused by T-cells, which are major components of the adaptive immune system whose roles include killing infected host cells, activating other immune cells, producing cytokines and regulating the immune response. They are the second level of the bodys immune system after antibodies that are meant to attach to the pathogen and stop it from infecting cells.

BBV152 induced binding (to both spike- and nucleocapsid protein epitopes) and neutralizing antibody responses that were similar to those induced by other SARS-CoV-2 inactivated vaccine candidates," the study showed, adding that a sizeable memory T-cell population was also observed three months after the second and final dose was given.

The vaccine was tested in 380 healthy children and adults as part of the phase 2 immunogencity study, with half of them getting a 3 microgram of antigen, along with adjuvant, and the rest getting twice that dose of antigen and the adjuvant.

The primary objective of the study was to determine seroconversionhow many of the participants showed antibodies in their immune systemwhile the secondary outcome was to determine the safety and side-effects.

Covaxin was shown to induce T-cell memory responses and showed the ability to make the body secrete spike-specific IgG antibodies. An inactivated vaccine is basically a dead coronavirus, with the company also using an adjuvant to boost the immune response.

A pre-print of the company safety data in phase 1 trials was also released last week. It showed that one of the nearly 300 participants who were part of the vaccine arms of the Covaxin phase 1 trial showed serious side-effect during the trial. The side-effect was deemed as not related to the vaccine, showing that the shots were safe to use.

The company said that the study had several strengths, including the fact that it enrolled participants with a wide range of ages and found no differences in immune responses across age groups.

Davinder Gill, a vaccine expert in the US, said in the phase 2 trial, Bharat Biotech seemed to want to fix the dose for its phase 3 trial and later, and found that the 6 microgram dose with the adjuvant was more effective at inducing the production of neutralizing antibodies.

Compared to the data that I have seen in other phase 2 studies from AstraZeneca, Pfizer and Moderna, Bharat Biotech for sure put out a lot more data. They have looked at various ways of measuring antibodies and various ways to look at neutralizing antibodies. But on the flipside, instead of more data, I would have liked to see a phase 2 maybe in 1,000-1,200 subjects, particularly because they were expanding the age group from 18-55 to 12-65 years," Gill said.

Bharat Biotech is currently conducting a phase 3 study of 26,000 participants to determine the efficacy of the vaccine.

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Covaxin found to be safe, effective in phase 2 trial - Mint

PALM BEACH, FL, Dec. 23, 2020 (GLOBE NEWSWIRE) -- Getting healthy is a popular resolution for the New Year, which is just days away.

The New Year is a perfect time for everyone to think about their health, said Marcus, founder and functional nutritionist for Health Addiction, a wellness company in Mexico City.The COVID-19 pandemic has forced people to think about their health.

During the past nine months, Ms. Marcus said Americans have searched for any health advantage that would boost their immune system and keep them healthy.

For the New Year, I want people to continue to prioritize their health. Make health your number one priority, Ms. Marcus said, adding that people should take a holistic approach to their health.

You should start eating healthy foods. Begin an exercise routine, she added.

Ms. Marcus, who knows that more than 70 percent of American consumers take dietary supplements for their health, plans to introduce eight popular functional supplements to the U.S. market this year.

Our Health Addiction supplements provide a holistic approach to keep people healthy, Ms. Marcus said. We have supplements that target the gut, immune system, cardiovascular health, and joints."

Health Addictionsfunctional supplements that will be available in the U.S. are:

We know people want to get and stay healthy, Ms. Marcus said. The New Year is the perfect time to begin a new health regimen. We branded our supplements, Health Addiction, because we want people to get addicted to good health. Now is an excellent time to start.

For more information, please visit Health Addiction online.

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New Year's Resolution is the Perfect Time to Add Health Addiction's Functional Supplements to Your Health Regimen - GlobeNewswire

NEW HAVEN As the COVID-19 pandemic enters its second year, neurologists are finding that patients frequently suffer difficulties in concentration and memory, even after recovering from the acute illness.

In some cases, chemicals formed to fight the coronavirus are causing bleeding in the brain and even strokes, though the instances of these are rare.

Dr. Serena Spudich, a neurologist with the Yale School of Medicine, is one of a team operating a neuro-COVID clinic, which has been see patients via telehealth visits. The clinic began seeing patients monthly, but now is run four times a month. There have been about 30 patients seen so far, Spudich said.

As the pandemic has progressed, we started to realize that there seemed to be some impact in the nervous system and that was something that other clinicians, other investigators in Asia and Italy and the United Kingdom were seeing, Spudich said.

The neurological issues patients were having after the major COVID symptoms had gone were so frequent that a specialized clinic was created within the Yale Medicine practice, including Dr. Shelli Farhadian and Dr. Lindsay McAlpine.

We wanted to get prepared because we realized there would be a variety of conditions that patients would be coming in with, Spudich said.

Headache has been one of the most common complaints, some of them persistent or severe enough to interfere with daily living, Spudich said. Other issues contribute to brain fog.

The primary concern is the sense that they are having trouble with concentration, memory and daily functioning in their lives, Spudich said.

Patients reported that they could not focus on their work or studies or had difficulty falling asleep or waking up.

Many of these issues are fairly subtle for the patients, so they may be able to function on a daily basis, she said. But the range of neurological symptoms has been broad, including a burning sensation on the skin, weakness and visual changes.

Its not the majority that theyre so debilitated that they cant work, Spudich said. Perhaps a fifth suffer that severely.

For most, its really remarkable what people continue to work through, she said.

Besides physical symptoms, theres also a significant mental health issue that some patients are exhibiting, including depression, anxiety and post-traumatic stress disorder, Spudich said. Theres always been a link thats been presumed between brain inflammation and some mental health and mood disorders.

Dr. Arman Fesharaki-Zadeh, a behavioral neurologist and neuropsychiatrist, is part of the clinics team.

Its not necessarily the coronavirus that causes neurological problems. Often its the bodys attempt to fight off the infection, the doctors noted.

One major issue with COVID is it causes a lot of inflammation in the body, Spudich said. That triggers the bodys immune system, which releases cytokines, proteins such as interferon and interleukin.

While not necessarily a cytokine storm that overwhelms the body, the response still can cause problems when the chemicals pass through inflamed blood vessels into the brain.

It doesnt seem that the virus, SARS-CoV-2, which causes COVID, is robustly affecting the brain, which is good, but even though maybe the virus itself isnt attacking the brain the immune response seems to be causing these problems, Spudich said.

Many of these patients were seeing were never severely ill. They were never severely ill in the ICU, Spudich said, but the cytokines released by immune cells are enough to cause lingering aftereffects.

It may be that addressing immune issues would address all the underlying issues that were seeing, she said. Theres so much we dont know. This is all the best hazard of a guess. What were doing basically is trying to listen to each patients story, how sick were they, what kind of lab values did they have, how long were they sick, what they were treated with.

In some cases, COVID may have exacerbated neurological problems the patient had before; in other cases they could be new symptoms.

While the neuro-COVID clinic treats patients, Dr. Amit Mahajan, assistant professor of radiology and biomedical imaging at Yale School of Medicine, has been researching the effects of the disease on the brain, using CT scans and MRIs. He is corresponding author of a study in the American Journal of Radiology of patients in the New York metropolitan area at the beginning of the pandemic.

What Mahajan and his co-authors found was a number of brain bleeds and clots forming in the brains of COVID patients. The numbers are small. In another study, 8.4 percent of admitted patients had such severe symptoms, he said. The number would be lower if all COVID patients were scanned.

Most of the problems, the real serious problems that happen with COVID, are due to something called inflammation in the blood, Mahajan said. And a lot of the people have developed clots because of the inflammation If they go and occlude the vessels of the brain, they may cause a stroke as well.

Problems also develop when the bodys clotting and anti-clotting processes are out of balance. Then you can not only have clots, you can also have bleeding, Mahajan said. The problem can be made worse if a patient is given blood-thinning medication, he said.

Another issue is what Mahajan called post-infectious phenomena, in which an immune response to the infection can cause its own problems. And that would include things like Guillain-Barre syndrome, in which the immune system attacks the nerves, as well as multisystem inflammatory syndrome in children.

For more information about the neuro-COVID clinic, call 203-785-4085.

edward.stannard@hearstmediact.com

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Aftereffects of COVID-19 can cloud the brain, or even cause strokes - CT Insider

Non-invasive, wearable tech could usher in a new generation of personalized therapeutics. Unveiled ... [+] today, startup Nsos aims to treat rheumatoid arthritis by reinforcing the brains natural pathways.

They look like earbuds, feel like earbudsbut when you put them in, theyre completely silent. Thats because these earbuds arent for playing music or listening in on a video call. Instead, they deliver a finely-tuned electrical field to the brain.

Unveiled today, the earbud-like devices are a revolutionary rheumatoid arthritis treatment pioneered by neurotech startup Nsos.These wearable therapeutics may sound like science fiction. Even Nsos founder and CEO, Konstantinos Alataris, calls them a moonshot idea. But according to the data from Nsoss first clinical study, these devices are hardly far-fetched.

Normally, autoimmune diseases are treated with medication. In the case of rheumatoid arthritis, the current best treatments are over-the-counter pills like ibuprofen or prescription immunosuppressants like Humira. But these medications are not without side effects. And in the case of Humira, the medication must be injected under the skin, an uncomfortable routine for many patients. But what if there was a way to treat painful conditions like rheumatoid arthritis without pills or needles?

What if the medicine was electric?

Thats what Nsos is aiming to achieve through a novel therapeutic approach the company is dubbing e-mmunotherapy. If successful, this will be the first wearable, non-invasive treatment for an immune system disorder.

Neuroscience and immunology were once thought to be completely separate fields. But its now understood that these two systems are in constant communication with each other. The brain simultaneously generates thoughts and actions while taking care of critical functions like heartbeat and body temperature. It turns out that the brain also plays a major part in regulating inflammation. When these neural inflammation networks go haywire, it can result in immune system disorders like rheumatoid arthritis.

Nsos first e-mmunotherapy proof of concept works by sending electrical signals to the brain to reinforce its natural pathways. This is an opportunity to take a biological pathway, how the brain controls an overactive immune response, and restore it using an electrical field, mimicking the brain's language, says Alataris. So far, the companys wearable tech approach looks promising. Patients of the companys pilot clinical trial reported reduced severity of their rheumatoid arthritis symptoms comparable to the results of current medications.

Nsos Founder and CEO, Konstantinos Alataris, PhD.

Alataris already has deep experience in electrical therapeutics. He was previously the founder and CEO of Nevro, a company that produces subdural spinal cord stimulation devices for chronic pain. Similar startups, like Elon Musks Neuralink, rely on implanted electrode arrays. But this is the first time that electrical signals will be delivered through a fully external device.

If approved, these devices could dramatically simplify the treatment for inflammation-driven conditions. The earbuds would only need to be worn for a few minutes each day and the positive effects would increase over time. By reinforcing the proper neural pathways, the devices teach the brain to remember the positive changes. Not only does this provide sustained relief, it also hits closer to the root of the illness, addressing brain signals rather than chemical ones.

Nsos also recognizes the unique nature of each patients condition. Using machine learning, Alataris says the devices will eventually be able to deliver personalized electric fields depending on a patient's disease progression. Your therapy, your electrical field, your path sequence, at the end [they] will be different than mine, says Alataris.

With $16.5 million in funding led by Mayfield Fund, Nsos is already in process to test their devices in randomized control trials. If successful, the results will be submitted for FDA approval. But Alataris is clear that it will be years before these devices can be prescribed for patientsvalidation through data comes first. We don't want to step too far off. Were putting one foot in front of the other based on the data, says Alataris. With the increasing rise of scientific misinformation, establishing trust with the public through data is more important than ever.

If Nsos first devices are effective in retraining the brains inflammatory response, it could open the door to a wide range of therapeutic options. More and more conditions, from diabetes to mental health disorders, are being newly understood in the context of inflammation. Indeed, Nesos is already developing two more products to address migraine prevention and postpartum depression.

For Alataris, this is the next level of neuroscience. We are still at the very early stage of what is possible and what we can possibly do. To have these big dreams, you need data to stand on. We dont want to go chasing dragons here, but its a very exciting time, says Alataris. If validated, Nsos technology may be the first step towards a new future of therapeutics.

Im the founder of SynBioBeta, and some of the companies that I write about are sponsors of the SynBioBeta conference and weekly digest, including the Mayfield Fund. Thank you to Desiree Ho for additional research and reporting in this article.

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What If You Could Change Your Immune System By Wearing Earbuds? Meet The Startup That Could Make It Possible - Forbes

After the initial results of the Pfizer-BioNTech and Moderna vaccines exceeded even the wildest efficacy expectations, one could be forgiven for believing weve found the answer to reclaiming our lives from the grip of COVID-19. In reality, its a little more complicated.

Cases of reinfection are beginning to emerge, showing that protective antibodies may not have the longevity we were hoping for. This poses the question: Is it more important to elicit a robust antibody response, T cell response, or both? Secondly, what is the approach or delivery platform that will achieve the collective robust immune response to finally end the pandemic?

BioSpace spoke with a few companies that have some ingenious ideas at different stages of preclinical and clinical development.

First, Science 101:

The human body contains a B cell responsible for generating and secreting antibodies, which play the important role of blocking viruses. Antibodies do wane, however, and have the potential to become less effective if the virus mutates, which already appears to be happening as cases of COVID-19 reinfection begin to emerge.

Then there are T cells which come in two main types. Helper T cells (CD4+T cells) stimulate the B cells to make antibodies and help killer cells to develop. Killer T cells (CD8+ T-cells) act as a type of clean-up hitter, killing infected host cells and activating other immune cells, enabling viral clearance. Importantly, they can also turn into Memory CD8 T cells which provide a long-lasting immune response.

All of these play a critical role in the adaptive immune system response.

Viral clearance is what is so important to prevent transmission. In my mind, at least, the best way to stop a pandemic is not just to protect the blocking, but to clear the virus if it does get in and reduce transmission, said Dr. Patrick Soon-Shiong, head of NantWorks, the parent company of NantKwest Inc. and ImmunityBio, which are collaborating on a vaccine designed to elicit both an antibody and a T cell response.

Soon-Shiong went on to say that the vaccines currently in late phase development have focused mainly on eliciting a strong antibody response with the Spike (S) protein.

The S protein is the protein that would stimulate an antibody, as well as some level of T cells, but not very strong. The S protein is what every vaccine thats in Phase III right now, Moderna, Pfizer, AstraZeneca, Johnson & Johnson are targeting, because thats the antibody approach, he explained. In fact, none of the phase III protocols actually mention T cells. They do in an exploratory way, but not in a definitive way of measuring the T cells.

The NantKwest and ImmunityBio approach combines the commonly targeted S protein with the lesser known N protein (nucleocapsid protein) which is essential for the virus to survive. They are also using a second-generation adenovirus vector which precludes the possibility of the vaccine becoming ineffective after the first dose, a risk inherent in first-generation adenovirus vector vaccines.

NantKwest Senior Director of Infectious Diseases, Jeffrey Safrit, explained that the nucleocapsid is viewed as a particularly strong stimulator of cellular immunity and improves the generation of memory T cells. T cell mediated immunity has been shown to last significantly longer than antibody-mediated immunity, he added.

In an oft-referenced study published in Nature, Drs. Nina Le Bert and Anthony T. Tan at Duke-NUS Medical School in Singapore showed that patients who recovered from the SARS CoV-1 virus possessed long-lasting memory T cells 17 years after the 2003 outbreak. In addition, the T cells displayed robust cross-reactivity to the N protein of SARS-CoV-2.

This indicates that T cells may just be the ticket to widespread immunity.

The duo announced positive interim safety data from its Phase I dose study on November 10.

Aiming for a More Robust Antibody Response

Abpro Corp., a biotechnology company developing next generation antibody therapies for severe disease, is targeting a more robust antibody response with its therapeutic, ABP 300, which is based on neutralizing monoclonal antibodies.

The company recently completed a Phase 1 study in humans, which will read out in Q1 2021. It also announceddatafrom a challenge study in rhesus monkeyspublished inNature Communications, whichshowed that a single dose of ABP 300 blocks infection of SARS-CoV-2 in prophylactic treatment and clears the virus in three days in a therapeutic setting.

ABP 300 also displayed the potential to neutralize eight SARS-CoV-2 strains with reported high-frequency mutations. This could prove a critical asset in the long-term fight against COVID-19.

Abpro Executive Chairman and Co-Founder Ian Chan said that a neutralizing antibody is exactly the way it sounds. It basically prevents the virus from entering human cells.

Chan further explained that neutralizing antibodies can be an effective one-two punch as both a treatment and a prophylactic.

Neutralizing antibodies have shown that they may be potential first line therapies for mild-to-moderate patients. And then secondly, they can also be used as a preventative type of treatment as well, said Chan.

If someone has not yet received a vaccine or somehow [is] unable to generate an immune response after vaccination and gets infected, then a therapy will be needed. Together, vaccines and therapies will form a potent combination to help mankind get the pandemic under control.

Chan told BioSpace that Abpro would like to get the drug to patients early in 2021.

Targeting the T Cell Response

OSE Immunotherapeutics, a clinical stage biotech focused on controlling the immune system in immuno-oncology and autoimmune diseases, plans to launch the Phase I trial of its vaccine candidate, CoVepiT, in December.

CoVepiT is based on optimized peptides selected to induce a lasting sentinel T lymphocyte immune response against SARS-CoV-2. OSE Chief Scientific Officer, Nicolas Poirier, is adamant about the advantages of his companys T cell specific approach.

We are developing a vaccine that addresses the T cell response only, and the idea, or the advantage, of that strategy is that we are developing a long term or lasting protective response, Poirier said. We can unfortunately expect that the antibody protection will be transient because of what we learned from the past coronavirus infection. And of course, we do not yet have sufficient data from the first-generation vaccines to say that they will be protective from the longer term or midterm.

OSE researchers analyzed more than 46,000 SARS-CoV-2 samples from patients around the world to identify matching vaccine targets. They then compared these samples to SARS-CoV-1 and MERS in order to identify targets that had the best chance of remaining unchanged in the face of mutations or the emergence of another strain.

Preclinical data show that the vaccine activates T memory cell responses. OSE plans to initiate Phase I trials in December and anticipates clinical data early in 2021.

The Combination Approach

Heat Biologics Inc. in collaboration with the University of Miami, is developing a "combination" vaccine that stimulates both antibody and T cell responses. Founder and CEO Jeff Wolf sees the antibody and T cell approaches as a one-two punch to the coronavirus.

Personally, I think you need both, especially in elderly and patients with comorbidities, because these people are really the most impacted by this, Wolf said. I think its clear from the data thats out there, you have patients who have generated a robust antibody response and then they come down with a severe case of COVID months later. So even though people think they have protection, they really dont.

Heats vaccine works by engineering multiple protein regions of the SARS-CoV-2 virus into its proprietary gp96 platform to create combined antibody and T cell immunity. When delivered to the body through the vaccines cells, the gp96 protein is then able to show the SARS-CoV-2 proteins to the immune system in a powerful way that activates a power T cell response.

Heat has previously used the go96 platform in preclinical studies against Simian immunodeficiency virus (SIV), HIV, and the Zika virus.

In terms of long term immunity against SARS-CoV-2, only time will tell what the magic ingredients turn out to be, but when it comes to a deadly pandemic that has killed more than 1.4 million people globally and more than 260,000 in the U.S. alone, the verdict is clear: we need to cover all our bases with all of our antibodies and T cells on board.

Most read today on BioSpace:

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Biotechs Developing Innovative Ways to Activate the Immune System Against COVID-19 - BioSpace

Q: As we go into the winter months and illness chances increase, what can I do to boost my immune system?

A: Your question is on the minds of many consumers, as more people have been reaching for vitamin supplements and seeking out healthy foods to improve their immune system amid the COVID-19 pandemic. In fact, 77% of consumers say they want to eat healthier to boost their immunity during the pandemic, according to a study by Archer Daniels Midland, a Chicago-based, food-processing company.

Building and maintaining a healthy immune system starts with focusing on good nutrition, said Beth Stefura, a family and consumer sciences educator for Ohio State University Extension. OSU Extension is the outreach arm of The Ohio State University College of Food, Agricultural, and Environmental Sciences (CFAES).

Our bodys ability to fight infection and disease depends on our immune system, she writes in Live Well and Boost Your Immune System, a blog post at the Live Healthy Live Well website. Eat well by choosing nutrient-rich foods, she adds.

The site, which can be found at livehealthyosu.com, is a free information resource that offers science-based consumer information and insights. Its written by OSU Extension educators and specialists in family and consumer sciences who promote health and wellness.

In the blog post, Stefura lists multiple foods that can help boost your immune system, including foods rich in:

Vitamin D, which plays a wide variety of roles in boosting the immune system, including helping the body absorb calcium, which builds strong bones and prevents osteoporosis. Your muscles, nerves, the immune system, and many other bodily functions all require vitamin D to do their jobs properly. Good food sources of vitamin D include fortified milk and fortified orange juice; fatty fish such as salmon, tuna, and mackerel; eggs and egg yolks; mushrooms; beef liver; cheese; and fortified breakfast cereals.

Vitamin C, which is essential for the growth and repair of tissue throughout the body. Good food sources of vitamin C include kiwi, broccoli, tomatoes, berries, Brussels sprouts, cantaloupe, cauliflower, grapefruit, honeydew, kale, mango, nectarine, orange, snow peas, sweet potato and strawberries. Red, green, and yellow peppers are also great sources of vitamin C.

Beta carotene, which studies suggest may enhance immune cell function and has been shown to strengthen the bodys infection-fighting methods. Good sources of beta carotene include carrots, sweet potatoes, winter squash, mango, tomatoes, beets, broccoli, cantaloupe, green peppers, kale, mangoes, turnip and collard greens, nectarines, peaches and watermelon.

Zinc, which helps the immune system fight off invading bacteria and viruses and is key to optimal immune function. Foods containing zinc include red meat, seafood, sunflower seeds, pumpkin seeds, oysters, poultry, beans, nuts, whole grains and some fortified cereals.

Stefura also says that minimizing your intake of sugar, processed foods and alcohol, as well as managing stress and getting enough sleep is key to boosting your immune system.

Lack of sleep contributes to a variety of health concerns, including a weakened immune system, she writes. Seven to nine hours is recommended each day for adults, and children need eight to 14 hours depending on their age.

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Chow Line: Healthy ways to improve immunity - The Bryan Times

Although COVID-19 primarily attacks the respiratory system, the virus can affect almost every organ and tissues in the human body, including immune and digestive systems.

An approach to reduce the impact of COVID-19 on health and well-being includes looking after what you eat and your lifestyle.

The GMFH editing team had time to speak with INRAE Research Director Jol Dor on what have we learned from the last months on the role of nutrition and a healthy gut microbiome for reducing the risk of contracting COVID-19.

Not only do chronic conditions, promoted by unhealthy eating, clearly increase the risk of contracting or developing a more severe form of Covid-19, but also it is well established that these come with low-grade inflammation. It is also clear that anti-inflammatory drugs may beneficially contribute to avoid severe forms involving the so-called inflammatory storm* typical of severe Covid-19. It is hence reasonable to speculate that improving gut microbiota profile by personalized nutrition and supplementation known to improve immunity can be one of the prophylactic ways by which the impact of this disease can be minimized.

The risk of developing a severe form of Covid-19 is higher in older people, and in people of all ages with pre-existing medical conditions that share as a common feature an inflammatory context (heart or lung conditions, weakened immune systems, severe obesity, diabetes, asthma).

In this context, any means of promoting immune homeostasis could possibly be protective. For example, probiotics with the ability to protect from diarrhea or to reduce gut permeability could help.

The current concept is that the dialogue between the microbiota and the immune system is central to mechanisms of infection and expression of the disease in Covid-19. Alteration of natural defenses (immunosuppression, immunosenescence, low grade inflammation) will induce dysbiosis. In turn, altered natural defenses and altered microbiota may mutually sustain one-another, favoring uncontrolled inflammation. Persistence of dysbiosis following resolution of major symptoms could explain long and difficult recovery from associated symptoms (altered gut transit, joint pain, headaches, anxiety, allergic symptoms, loss of taste and smell).

The scientific literature on microbiota changes in the old age documents a loss of richness which is associated with diminished reactivity of natural defenses. With loss of microbiota richness, the ecosystem will be less robust to assaults such as infection. It will neither fight nor recover as well. If in addition natural defenses are also diminished, infectious bacteria or viruses will induce more severe consequences. In such contexts it is a good preventive attitude to take care of the microbiota with a rather high diversity of fibers, in other words a large variety of raw or cooked vegetables and fruits that may confer protective benefits on the gut barrier and thereby the microbiota. Ideally, one would want to include probiotics from food sources or in the form of supplements and micronutrients documented for their ability to protect from gut hyper-permeability, inflammation, oxidative stress and possibly visceral sensitivity. For instance, the combination of yogurt and fruits contributes to intake of beneficial probiotic bacteria and key nutrients associated with increased gut microbiota diversity, including prebiotic fibers, vitamins and minerals.

We are truly microbial, we are ecosystems and we live in symbiosis with our microbiota that provides numerous beneficial functions. Preserving the richness and functionality of our gut microbiota will certainly help and possibly reduce the risk of contracting or developing a severe form of Covid. We should see this as a preventive and protective measure that should in addition have many more benefits as it will reduce the risk of numerous chronic conditions.

* Proteins that play a role in signalling to other cells how to regulate their activity and function (fight off disease for example).** Meaning the absence of the virus in the organism.

See the article here:
Nutrition, immunity and COVID-19: what have we learned during last months? - Gut Microbiota for Health

We could all use a little extra immune support this year. And, if were being honest, we will probably need to keep our focus on immune support for quite a while to come.

While there are many ways to support our immune system, these are the supplements that I consider to be foundational for immune health.

Vitamin D: Study after study has shown that one of the most important things that we can do to support our immune system is to make sure that we have adequate vitamin D levels. Its much tougher to keep our vitamin D levels in a healthy range during the winter months due to lack of sunshine. Therefore, many health care providers suggest that we take a little extra vitamin D in supplement form in the winter. I usually suggest supplementing with somewhere around 5,000 iu per day in the colder months, but check with your doctor because they can fine tune your levels and suggest an amount that is right for you. If you find that it is tough for you to get your vitamin D levels into a healthy range, then talk with your doctor about adding supporting co-factors like magnesium and vitamin K2.

Vitamin C: Everybody knows we need vitamin C for a healthy immune system. And while many foods contain this important vitamin, I like to make sure to supplement with a little extra during the winter months just to make sure Im getting a reliable daily amount. I shoot for around 2,000 mg to 3,000 mg a day, and since vitamin C is usually found in its water-soluble forms, I suggest taking 1,000-mg tablets or capsules three times a day with your meals if possible.

Zinc: New research has been showing that we need to also be focusing on the amount of zinc we get daily. Low levels of this important mineral have been linked to a harmful inflammatory response during certain illnesses. Zinc is available in capsules, tablets, liquid and lozenges. All of those options are fine just try to get the one that you are most likely to keep up with. Personally I like the lozenges in the winter months because most lozenges contain other immune helpers like elderberry, echinacea and vitamin C. Try to supplement with between 15 mg and 30 mg per day.

We need to treat our immune systems with care, especially these days. So, give these simple supplements a try.

Travis Lemon is a certified herbalist and co-owner of Tulsi at The Market in Huntington. He has worked in the natural health and wellness industry for more than 14 years. He can

be contacted at travislemonmh@gmail.com.

See the article here:
Travis Lemon: Are you taking these immune heavy hitters? - Huntington Herald Dispatch

Dr. Jeff Hersh| Correspondent

Q: Whats the difference between the different COVID-19 vaccines?

A: Our immune system, both the innate and adaptive parts of it, is designed to identify and attack non-self, that is proteins -whether on the surface of a virus, bacteria, fungi, parasite or other cell, or other protein- called antigens.When these antigens attach to special receptors on certain specialized immune system cells, the bodys immune response is stimulated.

The innate immune system is a non-specific defense, where immune cells (natural killer cells and phagocytes) identify and then directly destroy invading substances (so this part of the immune system is especially active on the skin and in the gastrointestinal tract).

The adaptive (acquired or learned) system utilizes cells that produce antibodies (certain types of lymphocytes) to tag and destroy invading substances/cells (each antibody is specific for a particular antigen), which are then engulfed by other cells of the immune system (macrophages).The immune system will "remember"this antigen (the length of this memory depends on many things), so the body is prepared to fight off this invader again in the future.The goal is to have these be neutralizing antibodies, which will effectively destroy the invading antigen.

A vaccine works by "presenting"an antigen to the immune system to "prime"it so that it is ready to mount a response to a specific "invader." For the SARS-CoV-2 virus that causes the COVID-19 disease, the spike protein on the surface of the coronavirus has been a key candidate for an antigen to be used in a vaccine.So, how can the vaccine antigen be "presented"to the immune system?

Inactivated/killed virus vaccine: This approach uses a weakened/attenuated (the target virus is modified so it no longer causes illness) or inactivated (killed) virus (the target virus is treated so it can no longer invade cells and reproduce) in the vaccine. After injection, this manipulated virus presents itself (and its surface proteins, etc.) to the immune system.This is the approach used in the yearly flu (because the flu virus mutates rapidly a new vaccine is prepared each year), hepatitis A, inactivated poliovirus, rabies, MMR (Measles/Mumps/Rubella), chickenpox and many other vaccines. The challenge in this approach is to inactivate/kill the virus in a way which still allows the vaccine to stimulate a robust immune response.

Protein Based:This approach uses a specific protein in the vaccine to stimulate the immune system, and is used in the hepatitis B, shingles, human papillomavirus and many other vaccines.This approach can also be used to "prime"the immune system to respond to a disease-causing toxin that is produced by an invading organism (such as with tetanus or diphtheria).The challenge in this approach is to select an appropriate protein that allows the vaccine to stimulate a robust immune response.

mRNA and DNA Plasmid Based:In order to understand this approach (a new, novel approach to vaccine development) we need to understand how our cells produce proteins (the workhorses which control and execute the cells functions).The DNA in the nucleus of our cells (whether our own DNA or DNA that gets inside the cells nucleus by DNA plasmid transfer or even from a virus entering the nucleus) is an instruction set on how to build a protein The code for a specific protein in these instructions is transcribed (copied) to messenger RNA, mRNA, to be carried from the nucleus to the ribosomes (the protein manufacturing site in cells).This information is then translated (read and decoded) so the correct amino acid sequence can be manufactured (and then have some post-manufacturing manipulation done) to create the desired protein.Once the mRNA has done its job, it degrades.

This approach "teaches"some of the bodys own cells to produce a protein (or proteins) that will then prime the bodys immune system.One benefit of this approach is that the mRNA/DNA plasmid can be created simply by knowing the genetic sequence of the pathogenic virus (and figuring out the specific sequence that codes for a protein that would make an appropriate antigen), so the virus does not need to be inactivated/killed nor a specific protein manufactured in the laboratory.However, the specific protein selected must still be one that will stimulate an appropriate immune response.And the specifics of how to transfer the mRNA (the mRNA must be encapsulated in a lipid covered nanoparticle) or DNA plasmid into some of the bodys cells is a fairly new technology (although one that has been successfully used in other therapeutic approaches).

Viral Vector: In this approach a modified (so it carries the DNA of an antigenic protein from the target virus), inactivated virus (not the pathogenic target virus) is used to infect some of the bodys cells, getting into the cells nucleus but NOT integrating into the patients own DNA, to utilize the normal cell protein manufacturing apparatus (as described above) to create a desired protein to stimulate the immune system.The virus vector selected is one that most patients will not have been exposed to in the past, so their immune system does not respond to the viral vector itself.Conceptually this is similar to the mRNA/plasmid DNA approach above, except the cells are being used to produce an appropriate antigenic protein with the instructions transferred by the modified virus.Although this is also a fairly new approach for a vaccine, this technological approach has been used for a couple of decades in other therapeutic treatments.

All four of these approaches are being pursued to develop a vaccine for SARS-CoV-2. Since only the genetic sequence of the pathogen virus is needed to begin development of the mRNA/DNA and viral vector approaches, it is not surprising that these are the approaches furthest along in the development process, specifically the clinical trials utilized to verify that the vaccine is safe and effective.

Bottom line: a safe and effective vaccine is likely to be approved very soon. When that happens, I urge everyone to get vaccinated as soon as it is available for them. That is clearly the pathway to get us out of this pandemic and back to a more normal situation.

CORRECTION: Due to a reporting error on my part, my column of Dec.2, incorrectly stated the number of nurses who have died of COVID. The column should have stated that 1,700 health care workers have died of COVID, including 213 nurses. I apologize for the error. I did not look at the source for the data closely enough.

Jeff Hersh, Ph.D., M.D., can be reached at DrHersh@juno.com

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What's Up Doc? What's the difference between COVID-19 vaccines? - MetroWest Daily News

Dr. Vidan is here to share how we can keep our immune system healthy.

ST. LOUIS The colder weather is sticking around, and that means flu season is on its way while we are already dealing with a global pandemic. How do we protect ourselves and our families through all of it? Dr. Alex Vidan, owner of Vidan Family Chiropractic, has some recommendations for us.

Dr. Vidan is here to share how we can keep our immune system healthy. He mentions that Dr. Fauci recommends taking Vitamin D and Vitamin C to keep your immune system healthy. Dr. Vidan also says that University of Chicago Medicine recently found that there is a link between Vitamin D deficiency and the likelihood of being infected with COVID-19.

Dr. Vidan has high-quality supplements available in office, so if you are interested you can call 314-678-9355, or just text SHOW CD to the same number.

Vidan Family Chiropractic is located at 2230 South Brentwood Blvd. Give them a call at 314-678-9355 or visit drvidan.com.

THIS ARTICLE INVOLVES COMMERCIAL CONTENT. THE PRODUCTS AND SERVICES FEATURED APPEAR AS PAID ADVERTISING. FOR MORE INFORMATION, EMAIL US AT SMSL@KSDK.COM.

SHOW ME ST. LOUIS IS A PART OF 5 ON YOUR SIDE AND FEATURES ST. LOUIS EVENTS, COMPANIES, BUSINESS PEOPLE AND OTHER GUESTS FROM AROUND THE COUNTRY.

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Dr. Vidan has tips to keep your immune system healthy this winter - KSDK.com

The addition of CDK4/6 inhibition with trilaciclib prior to gemcitabine and carboplatin (GCb) chemotherapy significantly improved overall survival (OS) in patients with previously treated metastatic triple-negative breast cancer (mTNBC), according to final results of a randomized phase 2 trial (NCT02978716) presented at the 2020 San Antonio Breast Cancer Symposium.1

OS benefits were maintained across subgroup analyses and observed in patients irrespective of CDK4/6 dependence, immune signature, and PD-L1 expression status.

Subgroup analyses suggest that administering trilaciclib prior to GCb enhances antitumor efficacy, regardless of CDK4/6 dependence and PD-L1 expression. Furthermore, adding trilaciclib prior to GCb appears to preserve and enhance immune system function, Joyce OShaughnessy, MD, said in a poster presentation of the final analysis. These data support further investigation of the association between enhanced antitumor immunity and improved survival in patients with TNBC receiving trilaciclib prior to chemotherapy.

The randomized, open-label, multicenter study enrolled patients with mTNBC who had previously received up to 2 prior lines of chemotherapy for recurrent or metastatic disease. Patients were randomized equally to 1 of 3 groups: group 1 received gemcitabine and carboplatin chemotherapy alone on days 1 and 8, group 2 received trilaciclib prior to chemotherapy on days 1 and 8, and group 3 received trilaciclib on days 1 and 8 and prior to chemotherapy on days 2 and 9.

Treatment consisted of gemcitabine 1000 mg/m2 and carboplatin area under the curve 2 with or without intravenous trilaciclib 240 mg/m2 given over 30 (5) minutes prior to chemotherapy; the regimens were administered in 3-week cycles until progressive disease or unacceptable toxicity.

Progression-free survival (PFS) and OS were key secondary end points, but the primary end point of the study was the duration of severe neutropenia in cycle 1 and occurrence of severe neutropenia at any time during treatment. Additional analyses explored outcomes based on CDK4/6 and immune subtyping as well as by PD-L1 status.

A total of 102 patients were enrolled in the study, including 34 in group 1, 33 in group 2, and 35 in group 3. Baseline characteristics were considered to be similar between the arms.

Preliminary results of the study demonstrated that the mean duration of severe neutropenia was 0.8 days in group 1, 1.5 days in group 2, and 1.0 day in group 3. Severe neutropenia was reported in 26%, 36%, and 23% of the 3 groups, respectively.2

Although the myelosuppression was not significantly different with the addition of trilaciclib prior to chemotherapy, the OS results were encouraging.

The final results showed that the addition of trilaciclib prior to chemotherapy resulted in higher objective response rates (ORRs), longer PFS, and statistically significant improvements in OS compared with chemotherapy alone. Mature data from this study were consistent with the primary analysis, said OShaughnessy, who is co-chair of Breast Cancer Research and chair of Breast Cancer Prevention Research at Baylor-Sammons Cancer Center and The US Oncology Network.

As of the earlier May 15, 2020, data cutoff, the ORR was 29.2% in group 1, 50.0% in group 2, and 38.7% in group 3. Among all 68 patients who were treated with trilaciclib, the overall ORR was 44.3%.

In group 1, the median PFS was 5.7 months (95% CI, 3.3-9.9) compared with 9.4 months (95% CI, 6.1-11.9) in group 2 (HR, 0.62; 95% CI, 0.32-1.20; P = .2099) and 7.3 months (95% CI, 6.2-13.9) in group 3 (HR, 0.63; 95% CI, 0.32-1.22; P = .1816). The median PFS for all patients treated with trilaciclib was 9.0 months (95% CI, 6.4-11.3) (HR, 0.62; 95% CI, 0.36-1.10; P = .1291).

With the final data cutoff of July 17, 2020, the final OS results showed a median OS of 12.6 months (95% CI, 6.3-15.6) for patients in group 1. The median OS was not reached (NR; 95% CI, 10.2-NR) in group 2 (HR, 0.31; 95% CI, 0.15-0.63; P = .0016) and 17.8 months (95% CI, 12.9-32.7) in group 3 (HR, 0.40; 95% CI, 0.22-0.74; P = .0004). For all patients treated with trilaciclib, the median OS was 19.8 months (95% CI, 14.0-NR) (HR, 0.37; 95% CI, 0.21-0.63; P <.0001).

Tumors were retrospectively characterized for CDK4/6 subtyping by the PAM50 and Lehmann TNBCtype-4 signatures as either CDK4/6 dependent, independent, or variable/indeterminate. By the PAM50 signature, basal-like tumors have known CDK4/6 independence and HER2-enriched, normal-like, and luminal A/B tumors have variable dependence. According to the Lehmann TNBCtype-4 signature, luminal androgen receptor types have a known dependence and some basal-like and mesenchymal tumors have variable dependence.

By the PAM50 signature, in group 1 the median OS was 10.1 months. In group 2, the median OS was NR (HR, 0.30; 95% CI, 0.1-0.8; P = .0164). The median OS in group 3 was 22.3 months (HR, 0.32; 95% CI, 0.1-0.8; P = .0095). For groups 2 and 3 combined, the median OS was 22.3 months (HR, 0.33; 95% CI, 0.2-0.7; P = .003).

According to the Lehmann signature, the median OS in group 1 was 9.7 months. In group 2, the median OS was NR (HR, 0.18; 95% CI, 0.0-0.7; P = .0052). For group 3, the median OS was 15.3 months (HR, 0.49; 95% CI, 0.2-1.3; P = .1397). In groups 2 and 3 combined, the median OS was 15.3 months (HR, 0.32; 95% CI, 0.1-0.8; P = .008).

Antitumor efficacy outcomes were similar in patients with tumors characterized as CDK4/6 dependent, confirming that trilaciclib did not antagonize the antitumor effects of GCb in the CDK4/6-dependent population, OShaughnessy said.

Of 85 patients evaluable for PD-L1 expression, 49 (57.6%) were positive. The benefit of trilaciclib treatment was seen irrespective of PD-L1 status, but a larger OS benefit was seen for patients who were PD-L1 positive.

Within the PD-L1positive population, the median OS in group 1 was 10.5 months compared with 20.1 months in group 2 (HR, 0.38; 95% CI, 0.2-1.0; P = .037) and 32.7 months for group 3 (HR, 0.30; 95% CI, 0.1-0.8; P = .01). The combined trilaciclib groups had a median OS of 32.7 months (HR, 0.34; 95% CI, 0.2-0.7; P = .004).

In the PD-L1negative population, the median OS was 13.9 months in group, NR in group 2 (HR, 0.35; 95% CI, 0.1-1.2), 17.8 months in group 3 (HR, 0.55; 95% CI, 0.2-1.4; P = .198) and 17.8 months in combined groups 2 and 3 (HR, 0.48; 95% CI, 0.2-1.2; P = .093).

Both PFS and OS were increased with added trilaciclib prior to GCb regardless of patients immune subtypes or high/low immune-related gene expression.

When we assessed the effect of trilaciclib on the peripheral T-cell repertoire, we saw a significant decrease in Simpson clonality among patients receiving trilaciclib [P interaction = .012]. When patients were stratified above or below median Simpson clonality at baseline, there was a significant improvement in survival among patients with decreased clonality receiving trilaciclib [P = .02], OShaughnessy said. Survival also appeared to be improved among patients with a higher fraction of newly expanded T-cell clones who received trilaciclib [P = .3]. These data suggest the addition of trilaciclib to GCb activates T-cell immunity, potentially leading to the antitumor benefit observed in the study.

In a spotlight poster presentation, Cristina Saura Manich, MD, PhD, head of the Breast Cancer Program at the Vall dHebron University Hospital in Barcelona, Spain, noted that the trial was not powered to detect differences in OS, so a powered trial is needed to confirm these results.

As such, the developer of trilaciclib, G1 Therapeutics, has announced that a registrational trial for trilaciclib in combination with GCb chemotherapy in patients with mTNBC will begin in 2021. The combination will be explored in patients with mTNBC who have not received a PD-1/PD-L1 inhibitor being treated in the frontline setting, and in patients who have received a PD-1/PD-L1 inhibitor being treated in the second-line setting. A total of 250 patients are expected to be enrolled, with the majority in the frontline cohort.3

The primary end point of this randomized, double-blind trial will be OS with secondary end points of patient-reported outcomes, safety, tolerability, myelopreservation, and PFS.

References

Read more:
Trilaciclib Administered Prior to Chemotherapy Enhances Immune System Reaction in Metastatic TNBC - Targeted Oncology

LEXINGTON, Ky. (LEX 18) With COVID-19, flu season and winter weather starting to arrive, there are a lot of things right now that affect ones health. Having a strong, balanced immune system can help people stay healthy.

So that they're much less likely to get an infection or if they happen to get sick, they might have an easier time or an easier recovery, said Dr. Madeline Fisher with CHI Saint Joseph Health.

Overall, it's important to know the immune system is just that - a system, so there is no one magic trick to strengthening it. It comes down to a balance of healthy habits.

Dr. Fishers first tip is to maintain a healthy diet of whole foods, including fruits and vegetables. Vitamin supplements can help, but its better to get nutrients from a natural source.

Also making sure to drink enough water, so that your body is able to flush out any toxins that would be in your system, said Dr. Fisher.

Some people with certain health concerns may need supplements. Dr. Fisher says if thats the case, its important to consult with a doctor first.

Exercise is also important, but that can be difficult to keep up with during winter weather and gym restrictions. Dr. Fisher says even a short brisk walk every day or every couple of days can help.

Also, take advantage of colder temperatures to grab a blanket and head to bed a little earlier.

Making sure to get enough sleep so that you're well-rested so your immune system is able to fight off infections, said Dr. Fisher. The amount of sleep that someone needs can vary depending on the person, but most adults need eight or nine hours a night.

Other tips include minimizing stress, practicing frequent handwashing, and keeping up with regular doctor visits.

The rest is here:
How to keep your immune system strong this winter - LEX18 Lexington KY News

In trials these vaccines have shown to be at least 94% effective at preventing people from falling ill with Covid-19. But how safe is this new technology? We spoke to Michel Goldman, a professor of immunology and founder of the I3h Institute for Interdisciplinary Innovation in healthcare at the Universit Libre de Bruxelles in Belgium. Here are five things to know.

Vaccinessuch as the inactivated polio vaccine, or most flu vaccines, use inactivated virusesto trigger a persons immune system to respond to that disease-causing organism. In other vaccines, such as the hepatitis B vaccine, an individual protein made by that organism is injected instead to trigger a similar response.

mRNA vaccines, however, trick the body into making the viral protein itself which, in turn, triggers an immune response.

Although the COVID-19 vaccines made by Pfizer/BioNTech are the first mRNA vaccines to complete all clinical trial stages and be licensed for use, the technology has been around for a while.

Human trials of cancer vaccines using the same mRNA technology have been taking place since at least 2011. If there was a real problem with the technology, wed have seen it before now for sure, said Prof. Goldman.

Because the technology can be deployed extremely rapidly, and clinical trials have been so successful, mRNA platforms will be an important means of preparing for future epidemics, he says.

A concern that some have had about the mRNA vaccines is that they could change peoples DNA. But that idea is completely false and has no scientific basis, says Prof. Goldman.

The (vaccine)mRNA will not enter the nucleus of the cells, where our DNA is.

Once the injected mRNA enters a human cell, it degrades quickly and only stays in the body for a couple of days.This is why people need two injections to develop the best immune response, he says.

The highest risk right now (especially for vulnerable people) is not to be vaccinated.

Prof. Michel Goldman, Universit Libre de Bruxelles, Belgium

The novel coronavirus, or SARS-CoV-2, has a complex structure, and different parts of the virus trigger the immune system to produce different antibodies to neutralise the virus.

If an unvaccinated person catches the virus, they will produce antibodies that prevent the virus from entering human cells. They may also generate antibodies that do not have much impact. And in some cases, a person may produce antibodies which actually help the virus enter cells.

mRNA vaccines are much more specific. They are designed to only trigger an immune response to the viruss spike protein, which is just one component of the viral membrane and enables the virus to invade our cells.

To be sure this is the case, researchers are carefully monitoring that the vaccine does not trigger an unwanted immune response.

So far this has not been shown for the (Covid-19) vaccines. But it will remain important to ensure the immune response triggered by the vaccine is focused on the viral spike protein, said Prof. Goldman.

Vaccine trials take place in stages, starting with trials on animals, and then three trials on people Phase 1, Phase 2 and finally Phase 3.

The Pfizer/BioNTech vaccine Phase 3 trial involved more than 40,000 people. It began in July and will continue to collect efficacy and safety data for another two years.

Safety issuesthat would affect significant numbers ofvaccines mostly appear within two months, Prof. Goldman says.

However, after a vaccine is given to millions of people, very rare side effects that cannot be anticipated from clinical trials might develop, so researchers and regulators will be keeping a close eye on how the vaccine rollout goes. This will be especially important for Covid-19 vaccines based on innovative technology.

Regulatory agencies reviewed the data from Covid-19 vaccine trials more quickly than usual by looking at it on a rolling basis rather than only once the trials were complete, but they did not fundamentally change their rules. I really dont think that corners were cut in terms of safety, said Prof. Goldman.

The process was faster than usual because researchers had already built an mRNA platform a way of getting viral mRNA into the body for cancer and other vaccines under trial. It meant this could be put into action as soon as the genomic sequence of the virus was shared.

Companies and governments also took the risk of producing large numbers of vaccines even before the the first stages of experimentation had been completed, which meant they were ready to beginlarge human trials as soon as the results were in.

Its a financial risk, because if you were wrong all this is lost. Thats why the risk is shared between the private companies and the governments, said Prof. Goldman.

The vaccine partly works by inducing local inflammatory reactions to trigger the immune system. This means that its normal for many people to experience pain at the site of the injection and sometimes fever and discomfort for one or two days after the vaccine.

This is something that has not been advertised enough, says Prof. Goldman.

A November survey in 15 countries found 54% of people were worried about possible side effects from a Covid-19 vaccine.

One unwanted response to the Pfizer-BioNTech mRNA vaccine came to light during the first day of mass vaccination in the UK after two people with a history of significant allergies reacted to the injection. The UK regulatory authority updated its advice to specify that people with a history of anaphylaxis to medicine or food should not get the shot.

In the clinical trials, allergic reactions occurred in 0.63% of people given the Pfizer-BioNTech vaccine, and in 0.5% of people given a placebo.

My main concern is that people will use (possible side-effects) as an argument not to be vaccinated, said Prof. Goldman The highest risk right now (especially for vulnerable people) is not to be vaccinated.

Prof. Goldman was the first executive director of the Innovative Medicines Initiative, a partnership between the EU and the European pharmaceutical industry to speed up the development of, and access to, innovative medicines.

Read the original here:
Five things you need to know about: mRNA vaccine safety - Horizon magazine

The new coronavirus vaccine appears to be extremely effective - blocking serious illness entirely in randomized trials - and it has passed strict safety reviews and won emergency authorization from regulators in five countries so far, including the United States. But news bulletins in the past week provided a reminder that this remains a revolutionary pharmaceutical agent that will be scrutinized in the months ahead as shots go into arms.

Among the unknowns: To what extent does the vaccine prevent infection vs. simply preventing clinical illness?

Can a vaccinated person who becomes infected, but not sick, transmit the virus to someone else? Thats a pivotal factor in forecasting how rapidly the pandemic will be quashed once there is widespread distribution of vaccines.

Another unknown: How long will the protective effect of the vaccine last?

Scientists will also be vigilant for severe allergic reactions. Last week, two health-care workers in the United Kingdom who were among the first batch of people to get the vaccine after it was authorized developed anaphylaxis, a severe allergic response.

Both were known to have a history of severe allergic reactions, and both were treated and recovered. A third person reportedly suffered a rapid heartbeat. British authorities issued new guidance saying people with a history of anaphylaxis should consult with their doctor before taking the vaccine. Researchers do not know what substance in the vaccine formula triggered the severe allergic response.

When you make a decision to launch a vaccine like this, its not because you know everything, said Paul Offit, a pediatrician and vaccine expert at Childrens Hospital of Philadelphia and member of a Food and Drug Administration advisory panel that endorsed the vaccine Thursday. But he added, I think we know enough.

Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said Saturday, I dont think that the allergic reactions are even close to being a show-stopper for the Pfizer vaccine.

He said the criteria for participation in the random trials excluded people with a history of severe allergic reactions, and it is not surprising that, as the vaccine reached the general population, such rare allergic responses emerged. He said officials will continue to monitor the safety of the vaccines long after they have received emergency authorization.

Observation of safety does not end when you start administering vaccines to the general public, he said.

The big picture is that covid-19, the illness caused by the coronavirus, is a known killer, and has already taken nearly 300,000 lives in the United States and more than 1 million worldwide. Vaccines are essential to crushing the pandemic. U.S. public health officials hope at least 70 percent of the population will agree to be inoculated with one of the vaccines rolled out in the coming months.

I feel like were doing something historic, and theres multiple vaccines, and we should be able to lick this, said immunologist Stanley Perlman of the University of Iowa, who is also a member of the advisory panel that voted Thursday to bless the Pfizer-BioNTech vaccine.

But he acknowledged he is concerned about potential side effects that may not yet have been identified.

I worry about something coming up that we dont know anything about. The unknown, he said.

Two criteria for a good vaccine are effective and safe. The coronavirus vaccine technically named BNT162b2 and developed by industry giant Pfizer and BioNTech meets both standards, according to the professionals who have developed the vaccine, conducted randomized clinical trials and reviewed resulting data during the past several months.

It has received emergency authorization from the FDA and from regulators in the United Kingdom, Canada, Bahrain and Saudi Arabia. Another, similar vaccine frombiotechnology companyModerna is poised to be greenlighted by the FDA this week after a meeting of an advisory panel.

Data from the randomized Pfizer-BioNTech trial showed the two-dose vaccine to be 100 percent effective in preventing severe illness from covid-19.

But in roughly half the people who get the shot, it can produce modest side effects, including fever, headache, fatigue and pain at the injection site. Thats typical for most vaccines.

This is not a flaw or a failure, vaccine experts hasten to point out. Side effects are a sign the immune system is kicking into gear, as intended. Theyre a feature and not a bug, to borrow the language of computer programmers.

Things like fever or soreness at the injection site are normal, and actually they indicate that your body is reacting to the vaccine, which is what you want, said Ellen F. Foxman, an immunologist at the Yale School of Medicine. Thats a good thing.

Side effects were roughly the same in trial volunteers who got the vaccine and those who got a saltwater placebo.

The immune system needs a better public-relations team, because its just the immune system doing what it does, Offit said.

The newly authorized vaccine, like the Moderna shot, uses a synthesized scrap of genetic information, called messenger RNA, that is wrapped in a protective fat layer to keep it from disintegrating. When it goes into cells in the muscle of the upper arm, it incites cellular machinery to manufacture a protein that mimics the shape of the spike protein that protrudes from the surface of the coronavirus.

At no point, in this type of vaccine, is the coronavirus itself or even part of the coronavirus injected into the body. The body, in effect, becomes the vaccine maker, creating a new protein that triggers an immune response. The immune system manufactures antibodies that can disable anything with structural features resembling this protein - including the coronavirus.

Such a vaccine has never been deployed before.

Its very important to think about the whole picture, Foxman said. The vaccine prevents a disease that we know has a lot of bad outcomes, right? Mortality is an outcome - death.

She added, To me its very clear its very beneficial to avoid all the known problems of getting covid 19. I would take this vaccine in a minute if I were offered it.

Read the rest here:
Coronavirus vaccines can have side effects - that typically means they're working - Anchorage Daily News

Male and female Schistosomes.

Credit: Alaa. Source: creativecommons.org/licenses/by-sa/4.0>, via Wikimedia Commons https://commons.wikimedia.org/wiki/File:Couple_of_Schistosoma_mansoni.jpg

Schistosomes are a group of parasitic flatworms responsible for causing the neglected tropical diseases of intestinal and urinary schistosomiasis. According to the World Health Organisation, human schistosomiasis is prevalent across 78 countries, in both tropical and sub-tropical regions, and is estimated to affect over 200 million people globally. Schistosomiasis is also considered by the W.H.O. to rank second only to malaria among parasitic diseases in terms of prevalence and socioeconomic burden in an infected community.

The enormous public health and economic burden results in infected individuals and their families being stuck in a cycle of poverty; where they are unable to improve their health due to financial constraints, but also struggle to maintain economic productivity because of their poor health.

In large part, these health, economic and social consequences of schistosome infection are caused by chronic, long-term infections. Without treatment, these parasitic worms have been shown to be able to persist inside a human host for over a decade (here is a case where they had been present for over 38 years!), but how can they survive inside a hosts blood vessels for so many years?

Schistosome physiology enables long-term infection

Schistosomes have a hugely complex life cycle, with an intermediate snail host and a definitive mammalian host.

Upon mammalian host invasion, schistosomes transform through multiple body plans (Cercariae, Schistosomula and Adult), where they eventually reside in their mammalian hosts vasculature, pair with an individual of the opposite sex, and produce thousands of eggs.

However, this is not a happily ever after for our pair of parasitic worms. The hosts vasculature is an extremely hostile environment, brimming with a range of immune components and molecules, tirelessly trying to recognise, bind and kill the parasites. To survive for such a long time inside a human host, schistosomes have (had to) become master manipulators of their environment and display evolutionarily refined characteristics to ensure their long-term survival.

It is well documented that the Schistosome outer surface layers (the tegument) are crucially important in facilitating host immune evasion and maintaining long-term intravascular infection, as this area is highly accessible to immune molecules. However, the parasites digestive tract has now been found to be equally as valuable in helping the parasite to evade the hosts immune system.

The oesophageal gland is essential for survival inside the mammalian host

Jayhun Lee and colleagues at the Morgridge Institute for Research and Howard Hughes Medical Institute of UoW- recently published invaluable research into schistosome digestive tract development, potential mechanisms behind prolonged schistosomiasis infection, and methods of host immune system evasion.

The researchers found, much to their surprise, that an accessory organ of the schistosome digestive tract called the oesophageal gland (OG) develops before the rest of the digestive system. As the digestive system hasnt been fully formed, and blood feeding hasnt started yet, it led Jayhun and colleagues to suggest that the OG has a role in schistosome processes beyond just nutrient uptake and host blood digestion.

For example, the OG is known to secrete a diverse assortment of proteins and other molecules, many of which have unknown functions beyond their demonstrated host protein interaction capabilities. One hypothesis (increasingly being shown to be true) is that OG protein secretions can bind, block, and mop up host antibodies and certain other immune cells before they enter the schistosomes blind gut, acting as a barrier to the hosts immune system. This OG secreted protein barrier could prevent immune molecules from causing direct damage to the gut, or indirect damage by further enhancing the immune response.

In one of their experiments to test the role of the OG in parasite survival, FoxA (a Forkhead-box transcription factor), a key regulator in OG development and maintenance was knocked out using RNAi, resulting in the complete absence of a normal functioning OG.

These parasites lacking an OG were rapidly killed by the hosts immune system in normal immunocompetent mice. However, in mice genetically engineered to lack an immune response, the parasites without an OG survived- showing that, without the OG to mediate protection from the hosts immune molecules, white blood cells could gain access to the parasites gut, enabling recognition of parasite gut tissues, and significantly enhancing killing of the parasite from the inside out.

How can we take advantage of these mechanisms?

Identification of OG-secreted proteins (that manipulate the hosts immune system) and analysis of their interactions with host immune molecules could provide novel antigens with great potential as vaccine targets.

One such group of secreted proteins with considerable promise are the Venom Allergen-Like (VAL) proteins, a group found in a variety of other parasitic worms and organisms. Several VAL proteins have been shown to be released from the OG in Schistosoma mansoni, namely VAL-6, VAL-7 and VAL-13 proteins; however, the specific roles and exact functions of these proteins in the immune evasion process still remains largely unknown.

Additionally, the authors suggest that the identification of genes and proteins downstream of FoxA may help us to selectively disrupt the proper function of the OG, promoting and facilitating schistosome killing by the hosts immune system. Also, as the OG develops during schistosome larval stages, any therapeutic targets could be effective against both immature/larval stages and adult worms, something that the current drug of choice, Praziquantel, cannot do.

With future efforts and continued research into the OG and its associated protein secretions it is possible we may discover a highly promising, novel antigen with great promise as a vaccine target something that will be essential to control and eliminate this disease going forward.

Continue reading here:
Investigating the importance of the Schistosome digestive tract in host immune evasion, parasite survival and novel vaccine development - BugBitten -...

A new approach for COVID-19 testing that detects a distinct pattern of immune gene expression in infected individuals could be used as a check against possible errors generated by the standard tests that directly detect the SARS-CoV-2 virus.

Researchers from University of California, San Francisco (UCSF; San Francisco, CA, USA) and Chan Zuckerberg Biohub (San Francisco, CA, USA) have developed the new COVID-19 testing approach that measures a patients immune response for better diagnosis. The new testing approach analyzes completely different molecules - from the person infected, rather than from the virus that infects the person although it can be implemented using the same PCR technology on the same nasal swab samples. It could be used as a standalone test, or even combined into the same testing panels used in standard PCR tests to detect the virus. Combining the technologies could lessen the chances of false negative or false positive results, according to the researchers.

The UCSF scientists created three proof-of-concept versions of the new test - one based on readouts of gene activity from three key genes, one based on readouts from 10 genes, and one based on 27 genes. The tests independently detected COVID-19 infection in clinically confirmed cases, increasing in sensitivity with the number of genes included. The researchers aim to use one of these measures of gene activation both to flag false negative viral PCR tests, in which direct viral detection fails, and to rule out false positive results, which may arise from cross-contamination between samples in testing labs.

To determine which changes in gene activity were distinctive to SARS-CoV-2 infection the researchers first surveyed all the genetic material in swab samples from the upper respiratory tract, so that they could identify the most important and predictive indicators. The researchers examined samples from patients with respiratory symptoms who were tested for COVID-19 as a possible explanation of their illness. The tests showed many of the patients did have COVID-19, but some of them turned out to be infected with more common respiratory viruses (like the flu) or to be suffering from nonviral conditions.

With computer algorithms and a great deal of number crunching, the UCSF scientists were able to identify a distinct pattern of gene expression associated with a tamping down of specific immune responses that occurs early during SARS-CoV-2 infection. The changes differed from those seen in other viral respiratory infections or non-viral respiratory illnesses, allowing for a specific diagnosis of COVID-19. The pattern of immunosuppressive gene expression the researchers identified in COVID-19 may explain the stealthy nature of this highly transmissible virus, according to the researchers.

"Without even having to detect the virus itself, these tests to measure changes in the expression of immune-related genes can determine whether or not someone has COVID-19," said co-senior study author Chaz Langelier, MD, PhD, assistant professor in the Division of Infectious Diseases in the UCSF Department of Medicine.

"We have concluded from our work that there is an immunosuppressive effect taking place that prevents symptoms from developing early during infection despite high levels of viral replication. It's a brilliant strategy, if you're a virus," added Langelier. "Our findings of a diminished inflammatory response by the innate immune system suggest that treatments that suppress the immune system early during COVID-19 infection are unlikely to be beneficial."

Related Links:University of California, San Francisco Chan Zuckerberg Biohub

Read the rest here:
New COVID-19 Testing Approach That Measures Immune Response Can Be Combined with Standard PCR Tests for Accurate Diagnosis - HospiMedica

We can readily understand why investors are attracted to unprofitable companies. For example, although software-as-a-service business Salesforce.com lost money for years while it grew recurring revenue, if you held shares since 2005, you'd have done very well indeed. But the harsh reality is that very many loss making companies burn through all their cash and go bankrupt.

Given this risk, we thought we'd take a look at whether ISR Immune System Regulation Holding (STO:ISR) shareholders should be worried about its cash burn. In this article, we define cash burn as its annual (negative) free cash flow, which is the amount of money a company spends each year to fund its growth. Let's start with an examination of the business' cash, relative to its cash burn.

Check out our latest analysis for ISR Immune System Regulation Holding

A company's cash runway is the amount of time it would take to burn through its cash reserves at its current cash burn rate. As at June 2020, ISR Immune System Regulation Holding had cash of kr49m and such minimal debt that we can ignore it for the purposes of this analysis. In the last year, its cash burn was kr28m. So it had a cash runway of approximately 21 months from June 2020. That's not too bad, but it's fair to say the end of the cash runway is in sight, unless cash burn reduces drastically. You can see how its cash balance has changed over time in the image below.

ISR Immune System Regulation Holding didn't record any revenue over the last year, indicating that it's an early stage company still developing its business. Nonetheless, we can still examine its cash burn trajectory as part of our assessment of its cash burn situation. Over the last year its cash burn actually increased by 4.9%, which suggests that management are increasing investment in future growth, but not too quickly. However, the company's true cash runway will therefore be shorter than suggested above, if spending continues to increase. ISR Immune System Regulation Holding makes us a little nervous due to its lack of substantial operating revenue. We prefer most of the stocks on this list of stocks that analysts expect to grow.

While its cash burn is only increasing slightly, ISR Immune System Regulation Holding shareholders should still consider the potential need for further cash, down the track. Issuing new shares, or taking on debt, are the most common ways for a listed company to raise more money for its business. One of the main advantages held by publicly listed companies is that they can sell shares to investors to raise cash and fund growth. We can compare a company's cash burn to its market capitalisation to get a sense for how many new shares a company would have to issue to fund one year's operations.

ISR Immune System Regulation Holding's cash burn of kr28m is about 14% of its kr195m market capitalisation. Given that situation, it's fair to say the company wouldn't have much trouble raising more cash for growth, but shareholders would be somewhat diluted.

Even though its increasing cash burn makes us a little nervous, we are compelled to mention that we thought ISR Immune System Regulation Holding's cash runway was relatively promising. While we're the kind of investors who are always a bit concerned about the risks involved with cash burning companies, the metrics we have discussed in this article leave us relatively comfortable about ISR Immune System Regulation Holding's situation. On another note, ISR Immune System Regulation Holding has 4 warning signs (and 2 which make us uncomfortable) we think you should know about.

Of course ISR Immune System Regulation Holding may not be the best stock to buy. So you may wish to see this free collection of companies boasting high return on equity, or this list of stocks that insiders are buying.

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This article by Simply Wall St is general in nature. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. We aim to bring you long-term focused analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Simply Wall St has no position in any stocks mentioned. *Interactive Brokers Rated Lowest Cost Broker by StockBrokers.com Annual Online Review 2020

Have feedback on this article? Concerned about the content? Get in touch with us directly. Alternatively, email editorial-team@simplywallst.com.

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We Think ISR Immune System Regulation Holding (STO:ISR) Can Afford To Drive Business Growth - Simply Wall St