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Archive for the ‘Immune System’ Category

Mom’s Mental Health During Pregnancy Tied to Baby’s Immunity – PsychCentral.com

Wednesday, March 4th, 2020

A mothers mental health during pregnancy has a direct impact on the development of her babys immune system, according to a new Canadian study published in the journal Clinical & Experimental Allergy.

Previous research has shown a link between a mothers mental state and the development of asthma and allergies in her babies, but this is the first study in humans to identify the mechanism at work.

Our study shows that what happens to the mother during pregnancy could affect the levels and function of the cells that produce immunoglobulin in children, said Dr. Anita Kozyrskyj, a pediatric epidemiologist and a leading researcher on gut microbes at the University of Alberta (U of A).

The research team analyzed the health records of 1,043 mother-infant pairs who were participating in the CHILD Cohort Study, a project that follows the health of thousands of Canadian children into their teens.

The mothers completed regular questionnaires about their mood during and after their pregnancies, asking, for example, whether they felt sad or overwhelmed. Stool samples from the babies were examined for the presence of intestinal secretory immunoglobulin A (sIgA), an antibody that plays a crucial role in immunity.

This immunoglobulin is really important in the microbiome for developing oral tolerance to environmental antigens, said lead author Liane Kang, who conducted the study for her MSc and is now studying medicine at the U of A.

The findings show that moms who reported symptoms of depression during their third trimester, or persistently before and after the birth, were twice as likely to have babies with the lowest levels of immunoglobulin A in their gut. The mothers symptoms did not have to be severe enough for a clinical diagnosis of depression. No link was found with postpartum depression.

The results remained even when variable factors such as breastfeeding and antibiotic use by the mothers and babies were taken into account.

We know that women who have psychological distress are less likely to breastfeed and interact with their children, said Kang. Antibiotic use could also impact how the infant gut microbiome is developing.

Despite all these factors there was still a link between depression and lower immunoglobulin A in the infant.

Kozyrskyj noted that the lowest levels of immunoglobulin A were found in infants between four and eight months old, when they would normally begin to produce their own immunoglobulin.

The largest impact of depression in the mothers was seen in this startup phase of the childs own immune system, she said.

Lowered immunity places the babies at risk for respiratory or gastrointestinal infections, as well as asthma and allergies, and may also lead to a greater risk for depression, obesity and autoimmune diseases such as diabetes, say the researchers.

Kozyrskyj suggests that higher levels of the stress hormone cortisol may be transferred from depressed moms to their fetuses and interfere with the production of cells that will make immunoglobulin after birth. She said more research is required to understand this link between the maternal microbiome and infant immune development.

New mothers are going through a very different stage in their life where they have to take care of another human being, and there are a lot of stressors that come with that, said Kang.

Both researchers said their study indicates that more mental health supports are needed for pregnant women.

These findings should not be used to blame mothers, said Kozyrskyj. Maternal mental health does not occur in isolation.

Source: University of Alberta Faculty of Medicine & Dentistry

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How to boost your immune system: 5 ways to fend off cold and flu symptoms – Real Homes

Wednesday, March 4th, 2020

Looking for advice on how to boost your immune system? Whether you find yourself coming down with colds more often than you'd like, or you are (understandably) worried about the Coronavirus, now is a pretty good time to give your immune system a bit of TLC. Late winter is a particularly common time for people to catch cold and flu because our immune systems have been depleted over the harsh winter months. Follow these steps to build up your immune defences and (hopefully) avoid catching anything.

For more health and beauty advice, visit out hub page.

Getting more sleep is probably the single best thing you can do for your health in general, and your immune system in particular. Even a single night of poor sleep or not enough sleep makes you more vulnerable to viruses and infections, to say nothing of chronic sleep deprivation.

Find our how to sleep well in our in-depth guide.

Food is another basic building block of your immune system: we need a varied diet not just to survive, but to keep healthy over time. Eating more vegetables, fruit, lean protein, and fibre has multiple health benefits, including strengthening the immune system. try to avoid processed and fas food as much as you can it's nutritionally poor and doesn't give your body enough of the vitamins and minerals it needs to function optimally.

If you're able to, try cooking at home more check our our food hub page for simple and inspiring recipes, most of which can be made in about half an hour.

While supplements cannot replace a healthy diet (you'll read this on every bottle and packet of vitamins), there are a couple of supplements that have been proven to improve your immune system. One of them is vitamin D, which the NHS recommends we all take between late autumn and early spring if we live in the Northern hemisphere.

The other is vitamin C but in order to get the real benefits, you might need to invest in more than fizzy vitamin C tablets. Look for Liposomal vitamin C instead it won't cure a cold that's already there, but it has been clinically proven to improve your immune system (and your skin, which is a bonus).

It is important not to rely on multivitamins to protect your from colds and flu, though sadly, it really doesn't seem to work that way.

Health Plus Vitamin D 400iu...

Yes, drinking more water boosts your immune system. It does so by improving your kidney function, allowing your kidneys to work more efficiently to flush out toxins from your body, making you less likely to fall ill. Water also helps increase blood supply to the brain, which in turn improves melatonin production that is essential for sleeping well.

There no need buy water for hydration, either tap water is perfectly fine and safe for you to drink. Just remember to refill your reusable water bottle.

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Aerobic exercise exercise that quickens your breath and increases your heart rate has been proven to boost your immune system by immunoglobulin (infection- and virus-fighting antibodies) levels in your blood. You should aim to do some form of exercise that makes you slightly out of breath every day. This doesn't have to mean going to the gym daily, but can include fast walking, swimming, gardening, and even cleaning.

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The Traditional Chinese Medicine Ingredients That Can Help To Boost Your Health – Hong Kong Tatler

Wednesday, March 4th, 2020

Photo: Courtesy of Dominik Martin via Unsplash By Kristy Or March 05, 2020

Whether youre trying to fight the flu or build up your immunity, these commonly used ingredients in Traditional Chinese Medicine will help keep you feeling at your best

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Traditional Chinese Medicine has been making its way back into the mainstream with the popularisation of more natural methods of achieving health and wellness. In Chinese medicine, Qi is the vital energy that helps regulate the body and keep it functioning normally. Any disruptions in the Qi are primarily seen as the source of physical and mental health issues including common ailments like the flu, fever, cough, depression and anxiety.We spoke to two Traditional Chinese Medicine practitioners - Gianna Buonocore from Integrated Medicine Institute and Cecilia Cheung from Health Wise- for advice on which herbs to add to your diet to help boost your immune system and improve your wellbeing.

The most commonly suggested ingredient by the two experts to add to your routine to boost your immunity is the Astragalus Root - or Huang Qi - as known in Chinese. The root is a principle herb used in Traditional Chinese Medicine for increasing an individuals vitality and promotes immune boosting compounds. Astragalus Root is typically combined with Atractylodes Rhizome (Bai Zhu) and Ledebouriella Root (Feng Feng) to create a soup. According to Cecilia Cheung, this soup is like building a defensive wall to protect your body from cold and flu and is generally good for everyone at all stages of life.

See also:Urban Escapes: Where To Find The Cleanest Air In Asia

Fresh ginger is often prescribed to boost the energy levels in individuals. According to Gianna Buonocore, it not only soothes an upset stomach but helps fire up your immune system and helps clear the pathogen by inducing sweat. Ginger has been used to treat many initial flu and heat symptoms like dry and sore throat, constipation and fatigue. It can also assist with promoting blood circulation and aids in relieving constipation, vomiting symptoms and morning sickness.

Garlic has been widely recognised for its many antibacterial, antiviral, antifungal and anti-inflammatory effects. The active ingredient inside garlic known as allicin, has antimicrobial properties which is activated through the action of chopping, crushing or chewing raw garlic - though Buonocore warns that these properties are destroyed during cooking. It is great for preventing and treating cold and flus, including relieving symptoms such as coughs, clear(ing) phlegm and enhanc(ing) immunity Cheung adds.

Chrysanthemum is a cooling herb and has antimicrobial properties which has a cleansing effect on the body and can help to clear pathogenic heat. Cheung describes chrysanthemums as a lung clearing herb as it is known to treat ailments like headaches, sore, throats, acne and ulcers. It has also been prescribed for issues like sleeplessness, strained eyes and high blood pressure.

Read more:In Good Health: How Traditional Chinese Medicine Is Evolving In Leaps And Bounds

Buonocore states that Goji Berries or Wolfberry Fruit are often used to improve health, vitality, longevity, energy and stamina. In Chinese Medicine, it is typically prescribed to treat poor eyesight, diabetes and anemia. Add them to your breakfast or include them in your tea for extra nutrients.

For those suffering from insomnia, restlessness, fatigue or loss of appetite, red jujube dates have often been used as a treatment by Chinese medicine doctors. The dates are said to have properties to calm the mind, reduce stress and decrease anxiety. Buonocore recommends a cup of jujube tea before bed (as it can) promote a restful nights sleep or treat insomnia.

See also:Hate The Gym? Here Are 8 Alternatives That You Can Try

In Chinese medicine, rose buds have a warming effect, and are used to alleviate abdominal pain, reduce indigestion, improve blood circulation in the body, and help to regulate menstruation and alleviate abdominal cramps. Buonocore suggests that rose bud tea can be combined with goji berries or red dates to combat tiredness, fatigue and sluggishness, however for those suffering from sore, dry throat, or constipation, Cheung recommends limiting your intake.

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Immune System May Provoke Salt Sensitive Hypertension in CDK – Spark Health MD

Wednesday, March 4th, 2020

Chronic kidney disease commonly known as CDK is a type of kidney disorder in which there is a gradual loss of kidney function and develops complications of high blood pressure and may also lead to heart attacks if the pressure of blood against the walls of blood vessels is not controlled. The new research reveals that the immune system has some link with hypertension.

The research team from TMDU (Tokyo Medical and Dental University) found that in patients of chronic kidney disease, the Tumor Necrosis factor (TNF- ) signaling factor of the immune system may provoke hypertension.

The complete study results are published in the journal Kidney International.

The immune system works very efficiently to provide protection against any pathogen that permeates the body to sustain normal health by finding out all the health-related threats, delivering the immune cells and changing the expression of a gene.

But the researchers from Tokyo Medical and Dental University (TMDU), Japan have discovered that there is a link between salt-sensitive hypertension and the immune system in individuals suffering from CKD (chronic kidney disease).

Also read- Mental Health of a Pregnant Mother may Influence the Immunity of her Unborn Child

Chronic kidney disease is a fundamental cause of about million deaths and has influenced over eight hundred million individuals worldwide. The substantial intricacy of chronic kidney disease is hypertension or high blood pressure.

The researchers have found that the development of CKD can be controlled by regulating normal blood pressure. High blood pressure is the main cause of CKD. Many individuals suffering from CKD have shown an increased sensitivity to salt. Increased salt sensitivity is a condition that is very hard to control because the salt intake from the diet has an excessive impact on blood pressure.

Salt sensitive hypertension is caused by a pathway known as WNK-SPAK-NCC phosphorylation cascade if over activated unsuitably because it causes increased reabsorption of salts in the kidney. it has not been assured that WNK-SPAK-NCC causes high blood pressure in patients of CKD or not and the regulation of phosphorylation cascade is still unknown.

Researchers used a diseased mouse model and found high levels of lysine deficient protein kinase 1 protein (WNK1) in the kidneys of mice suffering from CKD. High levels of WNK 1 protein causes an elevated triggering of the proteins SPAK and NCC. In mice suffering from CKD, the WNK-SPAK-NCC pathway stayed triggered when fed a diet with a high amount of salt, causing salt-sensitive hypertension.

The investigators also studied recent researches indicating that the immune system has a great impact on salt sensitivity. High levels of TNF- (a pro-inflammatory cytokine) were certain in the kidney of mice bearing CKD and stipulation of TNF- causes and elevated levels of WNK 1.

Also read- Duration of a Pregnancy is Linked With the Changes in Newborns DNA

Dr. Eisei Sohara, the first author of this study says that the transcription of WNK1 was not increased by TNF- but TNF- controlled the degeneration of mature WNK1 protein.

Normally a protein NEDD4-2E3-ligase degenerates mature WNK1 and it was found that TNF- increases the levels of WNK1 protein and prevents the transcription of protein that degenerates WNK1. Investigators confirmed the relation between salt sensitivity and immune system by restraining TNF- and found that the salt sensitivity of mice bearing CKD fed a diet with a high amount of salt was reversed.

The widely used antihypertensive drugs are thiazide diuretics that are NCC inhibitors but the effectiveness of these drugs vary among chronic kidney disease patients. Considerable response to thiazide diuretics is usually observed from individuals with high activity of NCC. The results of this research play a significant role to choose better NCC inhibitors in the future

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Redefining Cancer Treatment Shines Light on Cancer Immunotherapies – BioSpace

Wednesday, March 4th, 2020

KIRKLAND, QC, March 4, 2020 /CNW/ - Merck (NYSE: MRK), known as MSD outside the United States and Canada launches a new public awareness campaign about cancer immunotherapy, a type of cancer treatment that uses the body's own immune system to fight cancer.1 The campaign, Redefining Cancer Treatment, aims to raise awareness and inform Canadians about cancer immunotherapy by sharing the stories of four Canadians from different parts of the country and their personal journeys.

"When most Canadians think of cancer treatment, typically cancer immunotherapy is not on their radar," said AnnA Van Acker,President and Managing Director, Merck Canada. "The goal of this campaign is to help educate Canadians about the different types of cancer treatments to help empower us all to have more informed conversations with our caregivers."

Shannon, a B.C. local, is one of the patients featured in the campaign. In 2005, not long after she was married, Shannon was diagnosed with melanoma. Despite precautionary methods, she got pregnant. By 2011, her cancer had significantly progressed, and she and her husband were told there was a strong chance neither she nor her unborn child would survive.

"Having cancer was hard enough but learning that there was a strong chance that neither myself nor our child would survive was devastating," said Shannon. "Despite the odds, I gave birth to our daughter, and then started on cancer immunotherapy. Being a mother has changed my life and motivated me to help others with advanced cancer learn about the treatment options available."

The campaign will run on Facebook, YouTube and Twitter, and the patient stories will be also featured on the website, http://www.redefining-cancer-treatment.ca. Here, Canadians can learn more about different cancer treatment options and find useful resources for care and support.

"Cancer immunotherapy is a pillar in cancer care, alongside surgery, radiation and chemotherapy," said Dr. Krista Noonan, medical oncologist, B.C. Cancer Agency. "Continued research and development of cancer treatments are important and can contribute to improved outcomes for patients."

About Cancer ImmunotherapyCancer patients are treated with surgery, chemotherapy and/or radiation, and cancer immunotherapy. Immuno-oncology, a field of medical research which uses the body's own immune system to fight cancer, is an additional pillar in cancer-care treatment.2 Cancer immunotherapyis used to stop or slow the growth of cancer, stop cancer from spreading to other parts of the body, help the immune system work better to destroy cancer cells, and deliver toxins, such as radiation or chemotherapy, directly to cancer cells.3

There are several different types of cancer immunotherapy used to treat cancer.

Canadians are encouraged to visit http://www.redefining-cancer-treatment.ca to learn more.

About Merck CanadaFor more than 125 years, Merck, known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world's most challenging diseases in pursuit of our mission to save and improve lives. We demonstrate our commitment to patients and population health by increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to prevent and treat diseases that threaten people and animals including cancer, infectious diseases such as HIV and Ebola, and emerging animal diseases as we aspire to be the premier research-intensive biopharmaceutical company in the world.

In Canada, Merck markets a broad range of vaccines, pharmaceutical and animal health products and is one of the top R&D investors in Canada, with investments totaling $69 million in 2018 and more than $1 billion since 2000. Based in Kirkland, Qubec, Merck employs approximately 680 people across the country. For more information about our operations in Canada, visit http://www.merck.ca and connect with us on YouTubeand Twitter @MerckCanada.

SOURCE Merck

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Who is most at risk of contracting coronavirus? – The Guardian

Monday, February 24th, 2020

There have been a number of deaths from the coronavirus among doctors who are young and, as far as we know, otherwise healthy.

According to Dr Bharat Pankhania, an expert on communicable disease control at the University of Exeter Medical School, it is not surprising that some young, healthy people die after contracting the virus, noting the risk of infection and even death is not zero for any demographic.

All of us are at risk, and hence the superlative efforts at keeping containment in place, and keeping the virus from circulating as much as we can do, he said.

David Heymann, professor of infectious disease epidemiology at the London School of Hygiene and Tropical Medicine, agreed. This is a new disease in humans, so no-one has immunity health workers, like everyone else, dont have immunity, he said.

What is Covid-19 - the illness that started in Wuhan?

It is caused by a member of the coronavirus family that has never been encountered before. Like other coronaviruses, it has come from animals. Many of those initially infected either worked or frequently shopped in the Huanan seafood wholesale market in the centre of the Chinese city.

Have there been other coronaviruses?

Severe acute respiratory syndrome (Sars) and Middle Eastern respiratory syndrome (Mers) are both caused by coronaviruses that came from animals. In 2002, Sars spread virtually unchecked to 37 countries, causing global panic, infecting more than 8,000 people and killing more than 750. Mers appears to be less easily passed from human to human, but has greater lethality, killing 35% of about 2,500 people who have been infected.

What are the symptoms caused by the new coronavirus?

The virus can cause pneumonia. Those who have fallen ill are reported to suffer coughs, fever and breathing difficulties. In severe cases there can be organ failure. As this is viral pneumonia, antibiotics are of no use. The antiviral drugs we have against flu will not work. Recovery depends on the strength of the immune system. Many of those who have died were already in poor health.

Should I go to the doctor if I have a cough?

UK Chief Medical Officers are advising anyone who has travelled to the UK from mainlandChina, Thailand, Japan, Republic of Korea, Hong Kong, Taiwan, Singapore, Malaysia or Macau in the last 14 days and who is experiencing a cough or fever or shortness of breath to stay indoors and call NHS 111, even if symptoms are mild.

Is the virus being transmitted from one person to another?

Chinas national health commission has confirmed human-to-human transmission, and there have been such transmissions elsewhere.

How many people have been affected?

As of 20 Februrary, China has recorded 2,118 deathsfrom the Covid-19 outbreak.Health officials have confirmed74,576 casesin mainlandChinain total. More than 12,000 have recovered.

The coronavirus has spread to at least 28 other countries. Japan has 607 cases, including 542 from a cruise ship docked in Yokohama, and has recorded one death. There have also been deaths in Hong Kong, Taiwan, France and the Philippines.

There have been nine recorded cases and no fatalities to date in the UK. As of 17 February, a total of 4,501 people have been tested in the UK, of which 4,492 were confirmed negative.

Why is this worse than normal influenza, and how worried are the experts?

We dont yet know how dangerous the new coronavirus is, and we wont know until more data comes in. The mortality rate is around 2% at the centre of the outbreak, Hubei province, and less than that elsewhere. For comparison, seasonal flu typically has a mortality rate below 1% and is thought to cause about 400,000 deaths each year globally. Sars had a death rate of more than 10%.

Another key unknown is how contagious the coronavirus is. A crucial difference is that unlike flu, there is no vaccine for the new coronavirus, which means it is more difficult for vulnerable members of the population elderly people or those with existing respiratory or immune problems to protect themselves. Hand-washing and avoiding other people if you feel unwell are important. One sensible step is to get the flu vaccine, which will reduce the burden on health services if the outbreak turns into a wider epidemic.

Is the outbreak a pandemic?

A pandemic, in WHO terms, is the worldwide spread of a disease. Coronavirus cases have been confirmed outside China, but by no means in all 195 countries on the WHOs list. It is also not spreading within those countries at the moment, except in a very few cases. By far the majority of cases are travellers who picked up the virus in China.

Should we panic?

No. The spread of the virus outside China is worrying but not an unexpected development. The WHO hasdeclared the outbreak to be a public health emergencyof international concern. The key issues are how transmissible this new coronavirus is between people, and what proportion become severely ill and end up in hospital. Often viruses that spread easily tend to have a milder impact. Generally, the coronavirus appears to be hitting older people hardest, with few cases in children.

Sarah Boseley,Hannah DevlinandMartin Belam

Heymann said that who succumbs to the infection and who shrugs it off is often down to individual differences in the bodys response to the virus.

Some groups have a greater risk than others. At the moment it appears that people who are at greater risk are the elderly and probably the very young, said Pankhania.

But, he added, you cannot have that only the elderly and the very young will die, it is part of the natural history of such infections that we will get deaths across the age ranges The same pathophysiology can happen in the young as in the old.

In short, yes. It is not surprising that fellow clinical colleagues have got infected and some have died, said Pankhania, noting that medical professionals were in a special situation as they had multiple potential exposures to infection.

You have got infection control in place, however if you are forever being targeted, on the one rare occasion where your guard slipped, you get infected, he said. It is like being in the battlefield no matter how much protection you have, a stray bullet can catch you sometimes.

Such a slip, he added, was not surprising. A minor slip is eminently possible, especially when you are working under stress, you are tired, you have done long hours and your guard falls and you get infected, he said.

Pankhania said that at present it was thought there was only one form of the virus in circulation, so doctors were not being exposed to a more serious strain.

But Heymann said that if doctors did become exposed to the virus, it might be in a higher dose than would have occurred in a social context for example, they might come into contact with bodily fluids. If there is a massive inoculum of virus, that could make it a more overwhelming infection, he said.

That is a tricky question. Heymann said there was evidence that some patients in China infected with coronavirus also had flu at the same time. If that were the case, this could possibly increase the severity of a coronavirus infection, just because the body is already fighting [flu], and it might overwhelm the system, he said, but added that remained a theory.

However Heymann noted prior exposure to all sorts of bugs meant that health workers in general tended to have quite robust immune systems.

In a clinical setting you need full personal protective equipment, so you would be fully gowned, said Pankhania, adding that airtight masks were also used. You can only breathe through the filter on that mask.

Goggles were used, he added, noting it was possible to be infected through the eyes, while gloves were also important.

A colleague has to watch you put [the equipment] on and a colleague has to watch you take it off, and you would systematically put it on and systematically take it off, said Pankhania. Otherwise you risk contaminating yourself in the process of taking it off. But he added that under stress, mistakes could happen.

Pankhania said the 1918 flu pandemic offered one possibility, noting that some young people showed an exuberant immune response in other words, their immune system reacted too strongly to infection. In some cases, as yet poorly explained, poorly understood, the immune response is over the top that immune response then turns itself upon the persons body itself, he said, adding that could lead to fluid loss and organ damage. Buthe said it was not yet clear if this was at play in the current coronavirus outbreak.

The question remains open, but this week the World Health Organization director-general, Tedros Adhanom Ghebreyesus, told reporters that a number of trials were under way looking at the potential use of two HIV drugs as well as another antiviral called remdesivir that was developed to tackle haemorrhagic fevers including Ebola. Results, it seems, may be expected in three to four months. Meanwhile Columbia University researchers have received a $2m (1.5m) grant to work on possible antivirals drugs and antibodies to tackle coronavirus.

There are a lot of unknowns, including whether the virus could mutate to a more virulent form, while Pankhania said experts were still looking at the rate of deaths among those infected.

One key number is known as the R0, or basic reproduction number, which indicates how many new cases an infected person generates. At present it is thought to be about 2.6.

However, Pankhania said there was reason to be cautiously optimistic, noting that the figure might be lower outside of China, not least since other countries have had prior warning of the virus, while Wuhan is a densely populated city. He urged people in the UK to stay calm and said there was no reason to give up social events, quit the gym or keep children from playdates.

That is absolutely overreacting, he said. At this point in time there is no coronavirus circulating in the UK in a free way.

No, it is important to try to contain the coronavirus. A new virus has emerged out of the blue, said Pankhania, adding that it was believed to have started in bats, entered another animal and then passed to humans. It can not only infect humans, but be transmitted among humans and cause disease, he said. The upshot is the potential for a new virus circulating around the globe causing illness and death.

It is an extra burden on humanity, an extra infection in addition to influenza, and there is also an unknownness about it, which is we dont know how many people it could make very ill, we dont know how many people it will take, hence our concerns, he said.

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Who is most at risk of contracting coronavirus? - The Guardian

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Pandion Announces First Subject Dosed in a Phase 1 Clinical Trial of PT101, an IL-2 Mutein Fc Fusion Therapy for Autoimmune Disease – Yahoo Finance

Monday, February 24th, 2020

Trial to evaluate safety and tolerability of PT101, as well as expansion of regulatory T cells

Pandion Therapeutics, Inc., a biotechnology company developing modular protein therapeutics for autoimmune disease, today announced the dosing of the first subject in a Phase 1 clinical trial of PT101, a novel and proprietary interleukin 2 (IL-2) mutein Fc fusion protein therapy. PT101 has shown potential to treat autoimmune diseases by expanding populations of regulatory T cells.

"PT101, the lead program in our pipeline of modular protein therapeutics, has the potential to transform the standard of care for patients with a wide array of autoimmune diseases by modulating the immune system through the bodys natural mechanisms, rather than suppressing it," said Rahul Kakkar, MD, chief executive officer of Pandion. "We are extremely pleased to announce the commencement of this first-in-human trial less than three years after we launched Pandion and began discovery work on PT101."

The Phase 1 clinical trial will assess the safety, tolerability, and pharmacokinetics of PT101 in healthy volunteers and will include measures of its pharmacodynamic and immuno-modulatory activity. The trial is designed to demonstrate the safety of PT101 and confirm its ability to expand regulatory T cell populations in human subjects. Pandion intends to investigate PT101 as a treatment for patients with ulcerative colitis and other autoimmune diseases.

In preclinical studies, PT101 demonstrated highly potent and selective expansion of regulatory T cells across a broad dose range. Toxicology studies with PT101 further support a wide therapeutic window and no evidence of toxicity associated with treatment.

"Significant need remains in the treatment of many autoimmune and inflammatory conditions," said Jo Viney, PhD, chief scientific officer of Pandion. "Treatment with low doses of interleukin 2 to expand regulatory T cells has shown promise in treating autoimmune diseases, but a narrow therapeutic index and frequent dosing make such therapy challenging. PT101s novel, proprietary design has achieved high selectivity for the expansion of regulatory T cells. We look forward to evaluating PT101s safety and selectivity in the clinic this year."

About PT101PT101 is an interleukin 2 (IL-2) mutein Fc fusion protein therapy designed to potently and selectively expand regulatory T cells for the treatment of autoimmune disease. Pandions Phase 1 trial of PT101 is designed to assess the safety, tolerability, and pharmacokinetics of PT101 after subcutaneous administration, and will also include measures of regulatory T cell expansion and other pharmacodynamic measures.

About PandionPandion Therapeutics is developing modular biologics for autoimmune regulation that are designed to achieve lasting therapeutic outcomes for patients with autoimmune and inflammatory diseases. The company is developing its lead drug candidate, PT101, an IL-2 mutein Fc fusion protein that preferentially expands regulatory T cells, as well as a robust pipeline of systemic immune modulators and tissue-targeted therapeutics focused on the gut, liver, skin, kidneys, and pancreas. Pandions approach to developing modular proteins, antibodies and bispecifics includes two key elements: first, the innovative biologics are based on cutting-edge immunomodulators such as an IL-2 mutein or PD-1 agonist that work systemically by activating regulatory pathways of the immune system that suppress uncontrolled autoimmune responses; and second, these immunomodulators can be combined with tissue-selective tethers, building modular proteins and antibodies that target the precise location within the organ to deliver the desired effect. Pandion is backed by leading life sciences investors including Polaris Partners, Versant Ventures, Roche Venture Fund, SR One, BioInnovation Capital, and the JDRF T1D Fund. The company is headquartered in Cambridge, Massachusetts. Please visit http://www.pandiontx.com.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200224005192/en/

Contacts

Media:Kathryn MorrisThe Yates Network914-204-6412kathryn@theyatesnetwork.com

Investors:Sarah McCabeStern Investor Relations, Inc.212-362-1200Sarah.mccabe@sternir.com

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Q&A: The curious case of male pregnancy in seahorses and pipefishes – Horizon magazine

Monday, February 24th, 2020

She is studying three of the different types of pregnancy in syngnathids, a fish family including seahorses, pipefish and seadragons as part of a project called MALEPREG. One type is when eggs are glued to the body of the male, who then carries them; the second is full male pregnancy, with transfer of nutrients and oxygen in a placenta-like system including one in which a pouch closes with a skin fold upon egg deposition; and the third is similar to the second but with a closed pouch.

Beyond the novelty value, what is so interesting about studying male pregnancy?

When its a normal pregnancy system, egg production and pregnancy all intermingle with the mother, so its very difficult to differentiate what happens during egg development and pregnancy.

(Another) reason is that when we want to understand the evolution of a trait, when we only have the absence or presence of this trait then its very difficult to study how it has evolved. In syngnathids, what we have is that male pregnancy has evolved on a gradient so we have closely related species that do display different forms.

If we compare those, then we can understand, OK, these genes have (provided) the function for this and this, and now this has happened.

What exactly are you looking at?

One of the main issues were studying is the problem of the immune system. If you accept a non-self embryo because half is from the father and half from the mother in your body, then your body would in principle (reject it). (So for pregnancy to evolve), somehow this rejection has to be circumvented.

In mammalians, (certain immune system) genes are downregulated (during pregnancy) this is why we see that pregnant individuals are often sick. Then there are specific adaptations in the placenta that prevent the rejection of this non-self tissue. We are studying this in syngnathids.

We are doing a comparative genomics approach, so we have sequenced genomes of these different (syngnathid) forms. What we have found is that those genes are lost (in syngnathids with a part-closed pouch and changed in those with a closed one). So one arm of the immune system thats really important for vertebrates is (functionally) entirely lost.

What are the implications of that finding?

Our hypothesis is that this has permitted the evolution of male pregnancy.

When we look at fishes, in general, the parental investment strategies are completely different from humans males have a more important role. For the syngnathids, the problem is that they dont have a stomach, so they have to feed more or less permanently. They are always hunting food. So probably thats why they started to carry (their eggs) with them.

When we look at those species that are only carrying these embryos with them on the belly, those still have a (fully) functional immune system. Only with the evolution of this placenta-like structure full male pregnancy is this part of the immune system lost. Potentially, this (loss) has permitted this extreme evolution.

(Also), we have (here) a system that basically is immunologically deficient. (This) can ultimately help human medicine, because there are so many immunodeficiency diseases (such as HIV) and we are not able to cope with them. (It suggests that theres) a lot more flexibility in the adaptive immune system or in the evolution of adaptive immunity than we thought earlier.

What else have you found so far?

We did transplant experiments to understand better this self/non-self recognition. We transplanted fins (tissue) of the syngnathids to the belly of (themselves and others) to see if they rejected it or not and what we have found there is that those that have lost parts of their immune system are a lot better-accepting of non-self tissues.

We compared (syngnathid pregnancy) genes to the mammalian pregnancy genes, and we actually do find that these are genes from the very same pathways: similar genes have been co-opted in their function towards pregnancy.

(This) suggests that there are not probably so many options in what things have to be changed in their functions (to allow pregnancy). It doesnt really give us an idea of why (pregnancy) has evolved, but more that convergent evolution can come with a similar mechanistic basic.

What are you looking at next?

Now we know which genes might be involved (in the evolution of male pregnancy), but we dont know their function yet. The next step will be to (definitively) identify these.

Then we can study how (these genes) have evolved across the phylogeny (family tree of organisms) and see, for example, where there are mutations involved. We know that in (male) pregnancy they seem to have a role, but not if this is the same function as they have in female pregnancy.

Were (also) working on all the microbiota involved (in syngnathids brood pouches). Weve cultivated these microbes and now were going to deplete all the microbes on the male side and then add them again to see what their function is, to really understand this co-evolution of pregnancy with the immune system, but also with these microbes.

(With parts of the immune system lost, were studying in addition) how is it possible that these fishes can survive and fight against diseases? And what kinds of compensatory mechanisms might they have?

What wider lessons can we draw from studying male pregnancy in syngnathids?

In reproduction, I think we still (often) have the understanding that males are the ones giving the sperm and they dont then have a big function in parental investment. But we know now in terms of epigenetics (gene expression) that fathers are providing a lot more than just the sperm.

In the syngnathids, we really have the chance to see, OK, the males have this and this function. There are so many classical perceptions about how males have to behave and how females have to behave, (but it may not always be the case). We should really go beyond model systems. When we are driven to go and look at these weird creatures, we can (better) understand nature.

The research in this article was funded by the European Research Council. If you liked this article, please consider sharing it on social media.

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Enlivex Therapeutics Announces Plan for Increased Production Capacity of AllocetraTM in Preparation for Potential Treatment of Coronavirus (COVID-19)…

Monday, February 24th, 2020

Nes-Ziona, Israel, Feb. 24, 2020 (GLOBE NEWSWIRE) -- Enlivex Therapeutics Ltd. (Nasdaq: ENLV), a clinical-stage immunotherapy company, today announced that it is initiating a plan to increase its manufacturing capacity of AllocetraTM, following the first confirmed coronavirus (COVID-19) case in Israel, in preparation for potential requests for treatment of coronavirus (COVID-19) patients who are hospitalized with diagnosed organ dysfunctions or failures related to coronavirus.

AllocetraTM is an experimental therapy being investigated for treatment of patients with organ failure associated with sepsis, a syndrome whose lethal pathophysiology cytokine storm followed by organ failure is similar to that of the coronavirus (COVID-19).

Sepsis is the 3rdleading cause of mortality in the United States. One of every three patients who die in U.S. hospitals dies from sepsis. Organ failure resulting from sepsis, as well as in coronavirus (COVID-19), is considered the result of an exaggerated response of the immune system (cytokine storm) in the human body to an infection by a virus or a bacteria.

This exaggerated immune response results in organ damage. The immune attacks typically occur in vital organs such as lungs, heart, kidney and liver. When the organs become distressed, they begin to slowly dysfunction, which can result in organ failure, multiple organ failure, and mortality. Mortality rates from sepsis vary upon the degree of organ failure with which the patient arrived at the hospital. The literature describes an average of 20-40% mortality within 28-90 days for sepsis patients admitted to the ICU in a state of organ failure. Similarly, a cytokine storm was recently reported in patients with COVID-19 that were hospitalized in the ICU, (Huang et al. http://www.thelancet.com Published online January 24, 2020 https://doi.org/10.1016/S0140-6736(20)30183-5) and patients admitted to ICU had higher plasma levels of cytokines and chemokines.

There is no currently approved treatment for sepsis or for complicated corona virus infections. Enlivex recently announced the interim results from its first clinical trial in patients with sepsis. When compared with matched historical controls with sepsis from the same hospital, there were clear differences in (i) mortality -- none of the six Allocetra-treated patients died, vs 29% mortality in 28 days for the matched controls group; (ii) organ failure measures 78% of the matched controls had an increase of organ failure markers post admission to the hospital, while none (0%) of the six treated patients had any increase in organ failure score, despite similar presentation, and the average organ failure state of the matched controls worsened by a factor of two, while the treated group had not a single case of any organ failure increase; (iii) all the treated patients had their organ failures eliminated and they were subsequently released from the hospital. Each of the patients had organ dysfunction in two to five systems prior to administration of Allocetra. A Full summary of this trial is expected to be published in March 2020.

Enlivex has publicly announced its plan to initiate in 2020 two clinical studies: (i) a Phase II/III clinical trial for sepsis later in the year, and (ii) a Phase II/III for the prevention of GvHD in patients who undergo bone-marrow transplantations. The manufacturing capacity of Allocetra was planned to match the expected recruitment rate of patients in those two clinical trials.

To accommodate potential requests for treatment of COVID-19 patients who are hospitalized with diagnosed organ dysfunctions and/or failures, Enlivex has initiated a plan to increase the production capacity of Allocetra.

ALLOCETRATMby Enlivex was designed toprovide a novel immunotherapy mechanism of actionthat targets life-threatening clinical indications that are defined as unmet medical needs, includingprevention or treatment of complications associated with bone marrow transplantations (BMT) and/or hematopoietic stem cell transplantations (HSCT); organ dysfunction and acute multiple organ failure associated with sepsis; and enablement of an effective treatment of solid tumors via immune checkpoint rebalancing.

ABOUT ENLIVEX

Enlivex is a clinical stage immunotherapy company, developing an allogeneic drug pipeline for immune system rebalancing. Immune system rebalancing is critical for the treatment of life-threatening immune and inflammatory conditions which involve an out of control immune system (e.g. Cytokine Release Syndrome) and for which there are no approved treatments (unmet medical needs), as well as solid tumors immune-checkpoint rebalancing. For more information, visit http://www.enlivex.com.

Safe Harbor Statement: This press release contains forward-looking statements, which may be identified by words such as expects, plans, projects, will, may, anticipates, believes, should, would, intends, estimates, suggests, has the potential to and other words of similar meaning, including statements regarding expected cash balances, market opportunitiesfor the results of current clinical studies and preclinical experiments, the effectiveness of, and market opportunitiesfor, ALLOCETRATMprograms, which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that forward-looking statements involve risks and uncertainties that may affect Enlivexs business and prospects, including the risks that Enlivex may not succeed in generating any revenues or developing any commercial products; that the products in development may fail, may not achieve the expected results or effectiveness and/or may not generate data that would support the approval or marketing of these products for the indications being studied or for other indications; that ongoing studies may not continue to show substantial or any activity; and other risks and uncertainties that may cause results to differ materially from those set forth in the forward-looking statements. The results of clinical trials in humans may produce results that differ significantly from the results of clinical and other trials in animals. The results of early-stage trials may differ significantly from the results of more developed, later-stage trials. The development of any products using the ALLOCETRATMproduct line could also be affected by a number of other factors, including unexpected safety, efficacy or manufacturing issues, additional time requirements for data analyses and decision making, the impact of pharmaceutical industry regulation, the impact of competitive products and pricing and the impact of patents and other proprietary rights held by competitors and other third parties. In addition to the risk factors described above, investors should consider the economic, competitive, governmental, technological and other factors discussed in Enlivexs filings with the Securities and Exchange Commission, including under the heading Risk Factors contained in Enlivexs most recently filed Annual Report on Form 20-F. The forward-looking statements contained in this press release speak only as of the date the statements were made, and we do not undertake any obligation to update forward-looking statements, except as required under applicable law.

ENLIVEX CONTACT:Shachar Shlosberger, CFOEnlivex Therapeutics, Ltd.shachar@enlivex-pharm.com

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Masitinib Slows Disability Progression in PPMS and Non-active… – Multiple Sclerosis News Today

Monday, February 24th, 2020

AB Sciencesmasitinib significantly slowed disability progression in people with primary progressive multiple sclerosis (PPMS) and non-active secondary progressive MS (SPMS) at a lower dose of 4.5 mg/kg a day, top-line results from a Phase 2b/3 clinical trial show.

Masitinib, formerly known as AB1010, is an oral therapy that inhibits the activity of cells in the innate immune system, specifically mast cells, microglia, and macrophages. In doing so, the therapy is expected to limit the inflammatory processes that cause damage to the nervous system in MS.

It may also have applications in other conditions, including other neurological diseases and certain cancers.

People with primary progressive (PPMS) and non-active secondary progressive (nSPMS) forms of multiple sclerosis account for half of all MS patients, Patrick Vermersch, PhD, a professor at University of Lillein France and a trial investigator, said in an AB Science press release.

PPMS is estimated to affect about 15% of all MS patients, while non-active SPMS affects about 30% to 35%.

While numerous treatments based on targeting of B-cells and T-cells of the adaptive immune system are available for patients with relapsing forms of MS, these strategies have failed or had inconclusive results in PPMS and nSPMS. Consequently, there remains a very high medical need for people with progressive MS forms, Vermersch added.

In the AB07002 Phase 2b/3 clinical trial (NCT01433497), a group consisting of 301 MS patients were enrolled, with 200 randomized to 4.5 mg/kg of masitinib daily, and 101 to a placebo. The trials primary endpoint (goal) was changes in disability, measured through the Expanded Disability Status Scale (EDSS) score, from the studys start (baseline) through week 12 to week 96 of treatment.

Results showed the primary endpoint was met, with significantly lower increases in EDSS seen in the masitinib-treated group compared to the placebo group. This treatment effect was maintained for both the PPMS and non-active SPMS subpopulations. (Higher EDSS score represent worsening disability levels.)

Treatment also significantly delayed disease progression, as measured by the time to reach an EDSS score of 7.0 functionally, this score means a person requires the use of a wheelchair.

[T]he results from this study represent a scientific breakthrough because this is the first time that the novel strategy of targeting the innate immune system via mast cells and microglia has been able to significantly slow progression of clinical disability in progressive forms of MS, Vermersch said. These data are extremely encouraging, and may provide new hope for progressive MS patients.

Added Olivier Hermine, MD, PhD, president of AB Sciences scientific committee:This positive result in progressive MS is an important new finding that further validates the mechanism of action of masitinib in neurodegenerative diseases.

Masitinibs safety was consistent with the therapys known profile. Overall, 95% of people on 4.5 mg/kg masitinib daily, and 87.1% of those in the corresponding placebo group, experienced at least one reported adverse event. AB Science did not specify what these events were.

People in another trial arm were given masitinib a daily dose of 6.0 mg/kg, with titration starting at 4.5 mg/kg/day. This group consisted of 310 people, with 203 treated with masitinib and 107 given a placebo. No significant beneficial effects over placebo with masitinib at this higher dose were seen.

Further details were not released, which AB Science said would be given at an upcoming scientific conference. The company also announced a new patent filing for masitinib based on AB07002 trial results, and said it will be in contact with regulatory authorities to discuss further development of masitinib as a treatment for progressive forms of MS.

Masitinib is also being tested patients withamyotrophic lateral sclerosis (ALS), where a single-site Phase 3 trial (NCT03127267) is expected to open in March in Montreal, Canada. A Phase 3 trial (NCT01872598) in people withAlzheimers diseaseor probable Alzheimers also recently concluded.

This MS trial is the second piece of supportive evidence delivered by the masitinib clinical program. The first one was thepositive Phase 2B/3 study with masitinib in amyotrophic lateral sclerosis, Hermine said.

The two studies taken together clearly demonstrate that targeting the innate immune system via macrophage/microglia and mast cells, as masitinib does, is one of the right strategies to treat neurodegenerative disorders, Hermine concluded.

Marisa holds an MS in Cellular and Molecular Pathology from theUniversity of Pittsburgh, where she studied novel genetic drivers ofovarian cancer. She specializes in cancer biology, immunology, andgenetics. Marisa began working with BioNews in 2018, and haswritten about science and health for SelfHacked and the GeneticsSociety of America. She also writes/composes musicals and coachesthe University of Pittsburgh fencing club.

Total Posts: 1,053

Patrcia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.

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Harvard and the Guangzhou Institute of Respiratory Health Team to Fight SARS-CoV – Harvard Magazine

Monday, February 24th, 2020

Ever since the earliest reports of a pneumonia-like illness spreading within Hubei province in China, the resemblance to the SARS outbreak of 2002-2003 has been uncanny: probable origins in the wild-animal markets of China; an illness that in some people resembles the common cold or a flu, but in others leads to pneumonia-like symptoms that can cause respiratory failure; community transmission that often occurs undetected; super-spreader events; and reported vertical transmission in high-rises or other living spaces where the waste systems are improperly engineered or drain catch-basins are dry, allowing aerosolized particles to pass from one floor of a building to another (see The SARS Scare for an in-depth description of the epidemiology and virology of the SARS outbreak of 2002-2003 and the four independent zoonotic transmissions of 2003-2004).

At first, this latest outbreak was referred to as a novel coronavirus, then in the media as COVID-19 (formally, the name for the disease in an infected person who has become sick, a distinction analogous to that between a person who is HIV positive and one who has developed AIDS). Now that the virus has been characterized and its relationship to SARS firmly established, its designation is SARS-CoV-2severe acute respiratory syndrome coronavirus 2.

Will public-health measures be sufficient to contain its spread? How infectious is it? What is the incubation period? Is this a pandemic? What role does the immune-system response play in the progression of the disease? Which populations are most at risk? Can scientists develop a vaccine, and how quickly? These are some of the questions that scientists worldwide are asking, and that a collaboration among Harvard University and Chinese researchers will address as part of a $115-million research initiative funded by China Evergrande Group, which has previously supported Universitygreen-buildings research at the Graduate School of Design, research onimmunologic diseases, and work inmathematics. (See below for the University press release describing the initiative.)

Harvard Magazinespoke with some of the researchers involved in fighting the first SARS outbreak, and those who will be collaborating with Chinese colleagues, in what is already a worldwide effort to control SARS-CoV-2.

Michael Farzan 82, Ph.D. 97, who in 2002 was an assistant professor of microbiology and molecular genetics at Harvard Medical School (HMS) studying the mechanism that viruses use to enter cells, was the first person to identify the receptor that SARS used to bind and infect human cells. SARS-CoV-2 is a close cousin to SARS, and uses the same human receptor, ACE2, reports Farzan, who is now co-chair of the department of immunology and microbiology at Scripps Research. The ACE2 receptor is expressed almost exclusively in the lungs, gastrointestinal tract, and the kidneys, which explains why the disease is so effectively transmitted via both the respiratory and fecal-oral routes.

But there are subtle differences in the new virus behind the current outbreak, he explained in an interview. The viruss receptor binding domainthe part that attaches to the human receptorhas undergone a lot of what we call positive selection, meaning there has been a good deal of evolutionary pressure on that region from natural antibodies, probably in bats or some other animal host that is a reservoir for this disease. So while the virus retains its ability to bind ACE2, Farzan explains, it no longer binds the same antibodies. That is unfortunate, because as the first SARS epidemic wound down, HMS professor of medicine Wayne Marasco had identified a single antibodyfrom what was then a 27-billion antibody librarythat blocked the virus from entering human cells. (Marasco is actively testing new antibodies, hoping to find one that will have the same effect on SARS-CoV-2.) Still, we are not starting from square one, says Farzan.

In animal studies,Remdesivir [a new and experimental antiviral drug] has seemed to work against SARS-like viruses, he says. Its effectiveness will probably hinge on getting it early enough, in the same way that the antiviral drug Tamifluis most effective against the seasonal flu when given to patients early in the course of infection.

And there is a reasonable hope that a vaccine canbe developed, Farzan adds, because the part of the virus that binds the human receptor is exposed and accessible, making it vulnerable to the immune systems antibodies. In addition, the viral genome is relatively stable. That means SARS CoV-2 wont evolve much over the course of an epidemic, so a vaccine that is relatively protective at the beginning of an epidemic will remain effective until its end.

Another reason for optimismdespite the long road to deploying any vaccine in humansis that the science that allows researchers to understand the viruss structure, life cycle, and vulnerabilities is progressing far more rapidly today than during the first SARS outbreak 17 years ago. So, too, is the understanding of the human immune response to the virus, and of the most effective public-health strategies based on the epidemiology of the disease.

When epidemiologists assess the severity of an epidemic, they want to know how effectively the disease can propagate in a population. The first measure they attempt to calculate is the reproductive number (R0)the number of people that an infected individual will in turn infect in an unexposed population, in the absence of interventions. When the reproductive number is greater than 1 (meaning each infected person in turn infects more than one other person), more and more people become infected, and an epidemic begins. Public-health interventions are therefore designed to lower the rate of transmission below 1, which eventually causes the epidemic to wind down. The second number epidemiologists focus on is the serial intervalhow long it takes one infected person at a particular stage of the disease to infect another person to the point of the same stage of the disease. The serial interval thus suggests how rapidly the disease can spread, which in turn determines whether public-health officials can identify and quarantine all known contacts of an infected individual to prevent their retransmitting the disease to others.

Marc Lipsitch, a professor of epidemiology at the Harvard Chan School of Public Health (HSPH), and director of the schoolsCenter for Communicable Disease Dynamics, helped lead one of the two teams that first calculated the reproductive number of SARS in the 2002-2003 outbreak. SARS had an R0 of 3, he recalls: each case led to three others. In that outbreak, about 10 percent of those who became sick died. The good news is that SARS CoV-2 appears to have a much lower R0 than SARS, ranging from the high ones to low twos, and only 1 percent to 2 percent of those who become sick have died. On the other hand, the serial intervalstill being worked outappears to be shorter, meaning the new virus has the potential to spread faster.

In the current epidemic, Lipsitch notes a further concern: the fact that the incubation-period distribution and the serial-interval distribution are almost identical. Thats a mathematical way of saying that people can start transmitting the virus even when they are pre-symptomatic, or just beginning to exhibit symptoms. That makes tracing and quarantining contacts of infected individualsa classic, frontline public-health measurenearly impossible.

Tracing, quarantining, and other public-health interventions, such as distancing measures (closing workplaces or asking employees to work from home, for example) proved sufficient to defeat SARS in the early 2000s. But with SARS-CoV-2, public-health measures alone may prove inadequate. Controlling this version of SARS may require antivirals, stopgap antibody therapies, and ultimately, vaccines, deployedtogetherwith robust public-health containment strategies.

Unfortunately, SARS-CoV-2 is almost certainly already a pandemic, Lipsitch continues: demonstrating sustained transmission in multiple locations that will eventually reach most, if not all places on the globe. The disease appears to be transmitting pretty effectively, probably in Korea, probably in Japan, and probably in Iran. He has estimated that 40 to 70 percent of the adult global population will eventually become infected.

That said, Infected is different from sick, he is careful to point out. Only some of those people who become infected will become sick. As noted above, only about 1 percent to 2 percent of those who have becomesickthus far have died, he says. But the number of people who areinfectedmay be far greater than the number of those who are sick. In a way, he says, thats really good news. Because if every person who had the disease was also sick, then that would imply gigantic numbers of deaths from the disease.

I'm very gratified, Lipsitch continues, to see that both China and Harvard recognize the complementarity between public health and epidemiology on the one hand, and countermeasure-development on the other hand. We can help target the use of scarce countermeasures [such as antivirals or experimental vaccines] better if we understand the epidemiology; and we will understand the epidemiology better if we have good diagnostics, which is one of the things being developed in this proposal. These approaches are truly complementary.

In the short term, Lipsitchwho has sought to expand the modeling activities of the Center for Communicable Disease Dynamics to better understand the current outbreaks epidemiologysays, It would be great toexpand collaborations with Chinese experts. Longer term, I see a really good opportunity for developing new methods for analyzing data better, as we have in previous epidemics. After the first SARS outbreak, for example, epidemiologists developed software for calculating the reproductive number of novel diseases; that software now runs on the desktop computers of epidemiologists around the world. And in 2009, during an outbreak of swine flu in Mexico, Lipsitch and others developed a method for using the incidence of the disease among awell-documented cohort of travelerswho had left Mexico, to estimate the extent of the disease among amuch larger and less well surveyedpopulation of Mexican residents.

What they found then was that the estimated number of cases in Mexican residents likely exceeded the number of confirmed cases by two to three orders of magnitude. The same method is being used to assess the extent of SARS-CoV-2 in China right nowso far without any hiccups. In the Mexican case, Lipsitchreports, the estimates suggested that severe cases of the disease were uncommon, since thetotal numberof cases was likely much larger than the number ofconfirmedcases. So I think we have learned from each epidemic how to do more things. And in between them, you solidify that less visible, less high-profile research that builds the foundation for doing better the next time. His group, for example, has been developing ways to make vaccine trials faster and better once a vaccine candidate exists.

A vaccine is the best long-term hope for controlling a disease like SARS-CoV-2. Higgins professor of microbiology and molecular genetics David Knipe, who like Lipsitch will participate in the newly announced collaboration, works on vaccine delivery from a molecular perspective. Knipe has developed methods to use the herpes simplex virus (HSV) as a vaccine vector and has even made HSV recombinants that express the SARS spike proteinthe part of the virus that binds the human ACE2 receptor. He now seeks to make HSV recombinants that express the new coronavirus spike protein as a potential vaccine vector.

But Knipe also studies the initial host-cell response to virus infection, which is sometimes called the innate immune response. And he has used HSV vectors that expressed the first SARS spike protein to study how it activates innate immune signaling. That is important because inSARS 1, initial symptoms lasted about a week, but it was the second phasecharacterized by a massive immune-system response that began to damage lung tissuethat led to low levels of oxygen saturation in the blood, and even death.The inflammation in the lungs is basically a cytokine storm, an overwhelming and destructive immune response thats the result of innate signaling, Knipe explains. So were going to look at that with the new coronavirus spike protein, as well. This could help to determine the actual mechanism of inflammation, and then we can screen for inhibitors of that that might be able to alleviate the disease symptoms.

The idea, he says, is to stop theinflammatoryresponse now killing people in the respiratory phase of the disease by targeting the specific molecular interaction between the virus and the host cell. This, he explains, aligns with one of the principal initial goals of the collaboration, which is to support research both in China and at Harvard to address the acute medical needs of infected individuals during the current crisis.

In the last days of 2019 and the first days after the New Year, we started hearing about a pneumonia-like illness in China, says Dan Barouch, an HMS professor of medicine and of immunology known for his anti-HIV work, whose lab has developed a platform for rapid vaccine development. (During the Zika virus outbreak of 2016, for example, his group was the first to report, within a month, a vaccine protective in animal models.) When the genome of the virus was released on Friday, January 10, we started reviewing the sequence that same evening, working through the weekend. By Monday morning, we were ready to grow it.

His concern about this latest outbreak was that the rate of spread seemed to be very rapid. In addition, the outbreak had the clinical features of an epidemic. We reasoned that this might make it difficult to control solely by public-health measures, he says, particularly because the virus can be transmitted by asymptomatic individuals. Thus, if the epidemic is still spreading toward the end of this year or early 2021, by which point a vaccine might be available, Barouch explains, such a remedy could prove essential. Historically, when viral epidemics don't self-attenuate, the best method of control is a vaccine.

Although Barouchs Beth Israel Deaconess Medical Center lab is working on DNA and RNA vaccines, a new technology that has the potential to cut vaccine development times in half, large-scale manufacturing using so-called nucleotide vaccines is unproven. That's why I think there needs to be multiple parallel vaccine efforts, he emphasizes. Ultimately, we don't know which one will be the fastest and most protective. At the moment, he reports, there are at least a half dozen scientifically distinct vaccine platforms that are being developed and he believes that vaccine development for this pathogen will probably go faster than for any other vaccine target in human history.

Ever since I graduated from medical school, he points out, there have been new emerging or re-emerging infectious disease outbreaks of global significance with a surprising and disturbing sense of regularity. There is Ebola. There was Zika. There were SARS, MERS; the list keeps growing. With climate change, increasing globalization, increasing travel, and population shifts, the expectation is that epidemics will not go away, and might even become more frequent.

In this global context, Barouch emphasizes the importance of a collaborative response that involves governments, physicians, scientists in academiaandin industry, and public-health officials. It has to be a coordinated approach, he says. No one group can do everything. But I do think that the world has a greater sense of readiness this time to develop knowledge, drugs, and therapeutics very rapidly. The scientific knowledge that will be gained from the vaccine efforts [will] be hugely valuable in the biomedical research field, against future outbreaks, and in the development of a vaccine to terminate this epidemic.

University provost Alan Garber, a physician himself, adds that Global crises of such magnitude demand scientific and humanitarian collaborations across borders. Harvard and other institutions in the Boston area conduct research on diagnostics, virology, vaccine and therapeutics development, immunology, epidemiology, and many other areas.With its tremendous range of expertise and experience, our community can be an important resource for any effort to address a major global infectious disease outbreak. Our scientists and clinicians feel an obligation to be part of a promising collaboration to overcome the worldwide humanitarian crisis posed by this novel virus.

The official Harvard press release follows:

Harvard University Scientists to Collaborate with Chinese Researcherson Development of Novel Coronavirus Therapies, Improved Diagnostics

At a glance:

Since its identification in December, the novel coronavirus has quickly evolved into a global threat, taking a toll on human health, overwhelming vulnerable health care systems and destabilizing economies worldwide.

To address these challenges, Harvard University scientists will join forces with colleagues from China on a quest to develop therapies that would prevent new infections and design treatments that would alleviate existing ones.

The U.S. efforts will be spearheaded by scientists at Harvard Medical School, led by DeanGeorge Q. Daley, working alongside colleagues from the Harvard T.H. Chan School of Public Health. Harvard Medical School will serve as the hub that brings together the expertise of basic scientists, translational investigators and clinical researchers working throughout the medical school and its affiliated hospitals and institutes, along with other regional institutions and biotech companies.

The Chinese efforts will be led by Guangzhou Institute of Respiratory Health and Zhong Nanshan, a renowned pulmonologist and epidemiologist. Zhong is also head of the Chinese 2019n-CoV Expert Taskforce and a member of the Chinese Academy of Engineering.

Through a five-year collaborative research initiative, Harvard University and Guangzhou Institute for Respiratory Health will share $115 million in research funding provided by China Evergrande Group, aFortuneGlobal 500 company in China.

We are confident that the collaboration of Harvard and Guangzhou Institute of Respiratory Health will contribute valuable discoveries to this worldwide effort, said Harvard University President Lawrence Bacow. We are grateful for Evergrandes leadership and generosity in facilitating this collaboration and for all the scientists and clinicians rising to the call of action in combating this emerging threat to global well-being.

Evergrande is honored to have the opportunity to contribute to the fight against this global public health threat, said Hui Ka Yan, chair of the China Evergrande Group. We thank all the scientists who responded so swiftly and enthusiastically from the Harvard community and are deeply moved by Harvard and Dr. Zhongs teams dedication and commitment to this humanitarian cause. We have the utmost confidence in this global collaborative team to reach impactful discoveries against the outbreak soon.

While formal details of the collaboration are being finalized, the overarching goal of the effort is to elucidate the basic biology of the virus and its behavior and to inform disease detection and therapeutic design. The main areas of investigation will include:

With the extraordinary scale and depth of relevant clinical and scientific capabilities in our community, Harvard Medical School is uniquely positioned to convene experts in virology, infectious disease, structural biology, pathology, vaccine development, epidemiology and public health to confront this rapidly evolving crisis, Daley said. Harnessing our science to tackle global health challenges is at the very heart of our mission as an institution dedicated to improving human health and well-being worldwide.

We are extremely encouraged by the generous gesture from Evergrande to coordinate and supportthe collaboration and by the overwhelmingly positive response from our Harvard colleagues, said Zhong, who in 2003 identified another novel pathogen, the severe acute respiratory syndrome (SARS) coronavirus and described the clinical course of the infection.

We look forward to leveraging each of our respective strengths to address the immediate and longer-term challenges and a fruitful collaboration to advance the global well-being of all people, Zhong added.

Harvard University ProvostAlan M. Garbersaid outbreaks of novel infections can move quickly, with a deadly effect.

This means the response needs to be global, rapid and driven by the best science. We believe that the partnershipwhich includes Harvard and its affiliated institutions, other regional and U.S.-based organizations and Chinese researchers and clinicians at the front linesoffers the hope that we will soon be able to contain the threat of this novel virus, Garber said. The lessons we learn from this outbreak should enable us to respond to infectious disease emergencies more quickly and effectively in the future.

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Youre Likely to Get the Coronavirus – The Atlantic

Monday, February 24th, 2020

The Harvard epidemiology professor Marc Lipsitch is exacting in his diction, even for an epidemiologist. Twice in our conversation he started to say something, then paused and said, Actually, let me start again. So its striking when one of the points he wanted to get exactly right was this: I think the likely outcome is that it will ultimately not be containable.

Containment is the first step in responding to any outbreak. In the case of COVID-19, the possibility (however implausible) of preventing a pandemic seemed to play out in a matter of days. Starting in January, China began cordoning off progressively larger areas, radiating outward from Wuhan City and eventually encapsulating some 100 million people. People were barred from leaving home, and lectured by drones if they were caught outside. Nonetheless, the virus has now been found in 24 countries.

Despite the apparent ineffectiveness of such measuresrelative to their inordinate social and economic cost, at leastthe crackdown continues to escalate. Under political pressure to stop the virus, last Thursday the Chinese government announced that officials in the Hubei province would be going door to door, testing people for fevers and looking for signs of illness, then sending all potential cases to quarantine camps. But even with the ideal containment, the viruss spread may have been inevitable. Testing people who are already extremely sick is an imperfect strategy if people can spread the virus without even feeling bad enough to stay home from work.

Lipsitch predicts that, within the coming year, some 40 to 70 percent of people around the world will be infected with the virus that causes COVID-19. But, he clarifies emphatically, this does not mean that all will have severe illnesses. Its likely that many will have mild disease, or may be asymptomatic, he said. As with influenza, which is often life threatening to people with chronic health conditions and of older age, most cases pass without medical care. (Overall, around 14 percent of people with influenza have no symptoms.)

Lipsitch is far from alone in his belief that this virus will continue to spread widely. The emerging consensus among epidemiologists is that the most likely outcome of this outbreak is a new seasonal diseasea fifth endemic coronavirus. With the other four, people are not known to develop long-lasting immunity. If this one follows suit, and if the disease continues to be as severe as it is now, cold and flu season could become cold and flu and COVID-19 season.

At this point, it is not even known how many people are infected. As of Sunday, there have been 35 confirmed cases in the U.S., according to the World Health Organization. But Lipsitchs very, very rough estimate when we spoke a week ago (banking on multiple assumptions piled on top of each other, he said) was that 100 or 200 people in the U.S. were infected. Thats all it would take to seed the disease widely. The rate of spread would depend on how contagious the disease is in milder cases. On Friday, Chinese scientists reported in the medical journal JAMA an apparent case of asymptomatic spread of the virus, from a patient with a normal chest CT scan. The researchers concluded with stolid understatement that if this finding is not a bizarre abnormality, the prevention of COVID-19 infection would prove challenging.

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TLR2 could be targeted to treat age-related macular degeneration – Drug Target Review

Monday, February 24th, 2020

Scientists have implicated toll-like receptor 2 (TLR2) in age-related macular degeneration and shown that knocking it out can improve symptoms in animal models.

Researchers have shown that toll-like receptor 2 (TLR2) may play a role in age-related macular degeneration (AMD), the most common cause of central-vision blindness in adults. The scientists suggest targeting TLR2 in the eye may be a future therapy for AMD.

The paper, published in Cell Reports, stated that AMD is associated with two biological processes; uncontrolled oxidative stress resulting in the formation of a bleach-like chemical in the retina and the tagging of cell contents with complement protein. These tags signal for the elimination of the cell contents.

The scientists suggest in this paper that these two processes are linked by TLR2. Found on cell surfaces, TLR2 recognises chemical signals from bacterial infections in the environment outside the cell and activates the immune system.

In the case of the eye, TLR2 appears to act as a sensor of oxidative-stress, recognising a chemical pattern that is generated during oxidation, rather than infection and triggering a signal cascade that ends in promoting the laying down of complement, explained first author on the paper, Dr Kelly Mulfaul, from Trinity College Dublin, Ireland.

Dr Sarah Doyle, study leader and assistant professor of immunology at Trinity, said: A function for TLR2 has not previously been reported in retinal neurodegenerative disease pathology but it is likely to play an important role, because when we remove TLR2 from our experimental model systems we reduce the level of complement and this has the effect of protecting cells that are essential for vision from dying.

With the continual increase in life expectancy outpacing the rate at which drugs for age-related conditions are developed new avenues of therapy are badly needed, so the fact that blocking this single protein can have such a protective effect in the eye is a particularly exciting discovery.

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Muddy issues: Mastitis and scours Ohio Ag Net – Ohio’s Country Journal and Ohio Ag Net

Monday, February 24th, 2020

By Christine Gelley, Agriculture and Natural Resources Educator, Noble County, Ohio State University Extension

We finally got some snow and freezing temperatures! At our house, we didnt get snow a single day that our Christmas decorations were up, but snow on Valentines Day was appreciated. Fresh snow provides a refreshing look to the landscape when it covers up all the muck and brown underneath it. However, those cold temperatures are still not lasting long enough to firm up the ground and as soon as we track through that snow, our break from reality is over.

Mud creates challenges with mobility both for our animals and equipment. Aside from complicating the logistics of caring for the farm, mud increases our risks for herd health complications too. Many producers have babies on the farm right now. It is important to watch out for signs of mastitis with the mothers and scours with the young.

Lactating animals are at greater risk of mastitis infections when it is muddy. Contaminants on the udder tissue can enter the mammary glands through the milk ducts and cause inflammation. Mothers with mastitis may not allow their young to nurse at the needed length of time or frequency due to pain. The udder may feel hard or hot. Many cases of mastitis occur and pass before we ever notice, but some more acute cases can cause lasting damage to the mothers mammary tissue and reduce the growth of her young.

As soon as possible after birth and if you are able, check that each teat produces colostrum (the first and most crucial milk). Getting colostrum into a newborn within the first few hours is critical for the long-term health of the animal. The best source of colostrum is from the newborns mother. If this is not possible, the next best choice is another mother of the same species from your farm. After that, the next best choice is a colostrum replacer. The nutrient composition of milk is different from species to species and there are diseases that can be passed through milk from farm to farm. Therefore, do not substitute across species or with milk from another farm.

In addition, do not pasteurize colostrum. It will denature the components that make it so special. If you have a mother that produces extra colostrum or in the unfortunate event that a mother dies giving birth or shortly after, milks as much colostrum from her as you can and freeze it. Thaw frozen colostrum/milk in a warm water bath, never in the microwave. For more tips consult https://u.osu.edu/beef or https://u.osu.edu/sheep by typing colostrum into the search bar. There are many helpful articles available on the OSU Extension Team websites that you can access 24/7.

Another very helpful article is by my colleague in Belmont County Dan Lima about scours. It can be viewed online at https://go.osu.edu/scoursbydan. In his article, Dan reminds us that muddy conditions put calves (and other young) at a higher risk of developing scours, which is most obviously noticeable as diarrhea. Scours can be caused by a variety of organisms present in mud. The most common being E. coli. Often the young will pick up the bacteria (or other pathogens) from mothers udder tissue while nursing. Scours can be very detrimental to young animals because it causes dehydration and weight loss.

Young that receive adequate amounts of colostrum at birth receive helpful antibodies from their mothers that provide the immune system responses needed to combat the pathogens that cause scours. Vaccines can be administered to mothers in the weeks before calving that can also increase immunity in their young to scours.

In both mastitis and scours cases, the best way to keep issues at bay is through prevention. Do everything in your power to provide a relatively clean birthing environment and promote healthy immune systems.

Cull mothers that do not adequately care for their young or that have poor udder structure. If the udders are not conformed to aid the young nursing, they will struggle. If the udder bag is abnormally saggy, there is a greater chance of contamination of manure on the teats. Make notes at birth and after regarding mothering capabilities and resist the urge to give too many chances to mothers that create problems for you. A mother that does not do her job is a liability rather than an asset and will likely pass those traits on to her young. For lasting success, only keep the assets on your farm.

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Why the Coronavirus Seems to Hit Men Harder Than Women – The New York Times

Friday, February 21st, 2020

The coronavirus that originated in China has spread fear and anxiety around the world. But while the novel virus has largely spared one vulnerable group children it appears to pose a particular threat to middle-aged and older adults, particularly men.

This week, the Chinese Center for Disease Control and Prevention published the largest analysis of coronavirus cases to date. Although men and women have been infected in roughly equal numbers, researchers found, the death rate among men was 2.8 percent, compared with 1.7 percent among women.

Men also were disproportionately affected during the SARS and MERS outbreaks, which were caused by coronaviruses. More women than men were infected by SARS in Hong Kong in 2003, but the death rate among men was 50 percent higher, according to a study published in the Annals of Internal Medicine.

Some 32 percent of men infected with Middle East Respiratory Syndrome died, compared with 25.8 percent of women. Young adult men also died at higher rates than female peers during the influenza epidemic of 1918.

A number of factors may be working against men in the current epidemic, scientists say, including some that are biological, and some that are rooted in lifestyle.

When it comes to mounting an immune response against infections, men are the weaker sex.

This is a pattern weve seen with many viral infections of the respiratory tract men can have worse outcomes, said Sabra Klein, a scientist who studies sex differences in viral infections and vaccination responses at the Johns Hopkins Bloomberg School of Public Health.

Weve seen this with other viruses. Women fight them off better, she added.

Women also produce stronger immune responses after vaccinations, and have enhanced memory immune responses, which protect adults from pathogens they were exposed to as children.

Updated Feb. 10, 2020

Theres something about the immune system in females that is more exuberant, said Dr. Janine Clayton, director of the Office of Research on Womens Health at the National Institutes of Health.

But theres a high price, she added: Women are far more susceptible to autoimmune diseases, like rheumatoid arthritis and lupus, in which the immune system shifts into overdrive and attacks the bodys own organs and tissues.

Nearly 80 percent of those with autoimmune diseases are women, Dr. Clayton noted.

The reasons women have stronger immune responses arent entirely clear, and the research is still at an early stage, experts caution.

One hypothesis is that womens stronger immune systems confer a survival advantage to their offspring, who imbibe antibodies from mothers breast milk that help ward off disease while the infants immune systems are still developing.

A stew of biological factors may be responsible, including the female sex hormone estrogen, which appears to play a role in immunity, and the fact that women carry two X chromosomes, which contain immune-related genes. Men, of course, carry only one.

Experiments in which mice were exposed to the SARS coronavirus found that the males were more susceptible to infection than the females, a disparity that increased with age.

The male mice developed SARS at lower viral exposures, had a lower immune response and were slower to clear the virus from their bodies. They suffered more lung damage, and died at higher rates, said Dr. Stanley Perlman, a professor of microbiology at the University of Iowa who was the senior author of the study.

When researchers blocked estrogen in the infected females or removed their ovaries, they were more likely to die, but blocking testosterone in male mice made no difference, indicating that estrogen may play a protective role.

Its an exaggerated model of what happens in humans, Dr. Perlman said. The differences between men and women are subtle in mice, its not so subtle.

Health behaviors that differ by sex in some societies may also play a role in disparate responses to infections.

China has the largest population of smokers in the world 316 million people accounting for nearly one-third of the worlds smokers and 40 percent of tobacco consumption worldwide. But just over 2 percent of Chinese women smoke, compared with more than half of all men.

Chinese men also have higher rates of Type 2 diabetes and high blood pressure than women, both of which increase the risk of complications following infection with the coronavirus. Rates of chronic obstructive pulmonary disease are almost twice as high among Chinese men as among women.

In the United States, women are more proactive about seeking health care than men, and some small studies have found the generalization applies to Chinese students at universities in the United States, as well.

In unpublished studies, Chinese researchers have emphasized that patients whose diagnoses were delayed, or who had severe pneumonia when they were first diagnosed, were at greatest risk of dying.

One study of 4,021 patients with the coronavirus emphasized the importance of early detection, particularly in older men. And men have been turning up in hospitals with more advanced disease.

But in areas of China outside Hubei Province, the disease's epicenter and where the majority of those affected are concentrated, the patterns are different: The disease appears to have dramatically lower mortality rates, and men are being infected at much higher rates than women, according to the Chinese C.D.C. analysis.

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Men may have a false sense of security when it comes to the coronavirus, said Akiko Iwasaki, a professor of immunology at Yale University who studies why some viruses affect women more severely.

Gathering and analyzing data about the new virus by sex is important both for the scientists studying it and for the general public, experts said.

Since the start of the outbreak, for example, public health officials have emphasized the importance of washing hands well and often, to prevent infection. But several studies have found that men even health care workers are less likely to wash their hands or to use soap than women, Dr. Klein said.

We make these broad sweeping assumptions that men and women are the same behaviorally, in terms of comorbidities, biology and our immune system, and we just are not, Dr. Klein said.

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Recently Discovered Immune Cell Type May Be Key to Improving Pancreatic Cancer Immunotherapy – On Cancer – Memorial Sloan Kettering

Friday, February 21st, 2020

Summary

Current immunotherapies dont work for most people with cancer. Researchers have identified an overlooked immune cell type that may react to targeted therapies to rally a more powerful immune response in more cancer patients.

Immunotherapy is showing great promise for treating cancer. But so far, this approach has been effective in only about 20% of all cancers. To advance those results, researchers are looking for new ways to mobilize the immune system to destroy tumors.

Most immunotherapy drugs act on one type of immune cells called T cells. Drugs called checkpoint inhibitorsrelease the brakes on these cells, spurring them to mount an attack against a tumor. Researchers have learned that checkpoint inhibitors seem to work best in people whose tumors have been invaded by T cells sensing some kind of threat from the cancer before the treatment is started.

The problem is that most tumors dont have many T cells in them. In order to design an immunotherapy that works on more people, researchers have been looking for additional immune cell types to rally against cancer.

Now, an MSK research team reports finding a promising candidate: a group of immune cells called innate lymphoid cells (ILCs). These cells are present in many different tissues and appear to have mild antitumor effects in their normal resting state. The researchers showed that activating ILCs with drugs mobilizes T cells to shrink pancreatic cancer tumors. This could be an important step, as pancreatic cancers have not responded to checkpoint inhibitor drugs.

We think this is an important finding both for pancreatic cancer research and cancer immunotherapy overall, says Vinod Balachandran, a surgeon-scientist affiliated with theDavid M. Rubenstein Center for Pancreatic Cancer Researchand a member of theParker Institute for Cancer Immunotherapy. We are learning there are multiple ways to use the immune system to fight cancer. We think this is a sign that new immunotherapies are on the horizon.

Dr. Balachandran made the discovery in collaboration with cancer immunologistsTaha Merghouband Jedd Wolchokof the Human Oncology and Pathogenesis Program. The finding is reported today in Nature.

This is a novel treatment that works together with one of the most successful immunotherapies we have today.

ILCs are part of the bodys innate immune system where immune cells are programmed to put up an initial defense against infections and other threats, and further amplify the immune response by activating T cells. But ILCs were discovered only 10 years ago, so they have not been the focus of immunotherapy efforts. Now, innate immune cells are beginning to draw more interest from the cancer-research community. Dr. Balachandran and colleagues investigated if and how these cells played a role in the bodys response to cancer.

For the Nature study, the team looked in human pancreatic tumors to see if ILCs were present. They saw that a subtype of these cells called ILC2s were present in larger numbers in tumors compared with normal organs, suggesting they were responding to the tumors. The researchers also found that pancreatic cancer patients with more ILC2s in their tumors lived longer, suggesting ILC2s possibly had an anticancer function.

The team then tested if ILC2s could help control tumors in mice. Removing ILC2s caused pancreatic tumors to grow faster.

We thought, if these cells have protective tendencies against cancer, maybe we can figure out ways to activate them, Dr. Balachandran says.

ILC2s have receptors on their surface that control whether they multiply. The researchers found that dosing the ILC2s with a protein called interleukin 33 (IL-33) activated them, and caused both them and T cells to expand, which in turn caused tumors to shrink. IL-33 did not shrink tumors in mice that didnt have ILC2s, proving the ILC2s were the key cells mediating the effects.

The research team then looked for ways to further amp up ILC2 antitumor activity. Checkpoint proteins on the surface ofT cells act as brakes to prevent them from attacking the bodys own tissues. But this also limits the T cells antitumor activity. As ILC2s are related to T cells, Dr. Balachandrans team wondered whether checkpoint proteins also acted as brakes on ILC2s.

Immunotherapy at MSK

Cancer is smart, but your immune system is smarter. Discover how Memorial Sloan Kettering is deploying immunotherapy to fight cancer.

They discovered that when activated by IL-33, ILC2sexpress an important checkpoint protein on their surface called PD-1. This has interesting immunotherapy implications: PD-1 is one of the most important brakes on T cells, yet PD-1-blocking checkpoint inhibitors have not worked well against pancreatic tumors. This suggested treating mice with IL-33 may make pancreatic tumors sensitive to PD-1-blocking checkpoint inhibitors.

When the researchers gave IL-33 plus a PD-1 inhibitor to the mice, the tumors shrank even more. Activating ILC2s by adding IL-33 appeared to be the key for PD-1 checkpoint inhibitors to work well against the mouse pancreatic tumors.

Dr. Balachandran and his team are currently working on developing a drug that can activate ILC2s in humans as the next step.

This is a novel treatment that works together with one of the most successful immunotherapies we have today, Dr. Balachandran says. This could be a way to sensitize cancers that typically would not respond to PD-1 checkpoint inhibitors.

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Dr. Katz: A healthy lifestyle will be best defense against coronavirus threat – Your Valley

Friday, February 21st, 2020

Dr. Steven Katz

(Photo by Aaron Kes Photography)

Dr. Steven Katz

Coronavirus is on the verge of being the next worldwide pandemic.

Thousands of people, mostly in China, have contracted the virus. However, at least two Arizonans are suspected of having the virus.

With no known cure for this virus, researchers are working furiously to find a way to treat those with this potentially deadly infection.

And while the world is focused on a cure, not enough of the conversation is focused on the things people can do to avoid contracting the disease.

Naturopathic doctors, however, are opting to address just that.

As with most of these epidemics, the people who generally die are the people with weak immune systems. Naturopathic physicians are combating this issue by using natural and safe approaches rather than through chemicals created in the lab that just suppress our immune systems.

Naturopathic physicians take a holistic approach to treating patients and eschew from prescribing pharmaceuticals unless deemed necessary. Just like conventional medical doctors, naturopathic physicians undergo a four year medical school doctoral program. The difference is that naturopathic physicians look to natural solutions to cure any of the bodys ailments.

And our solutions to avoiding diseases and viruses such as the coronavirus are particularly prescient today as the world confronts this pandemic. I have a practice in Scottsdale where I stress to my patients that the best way to fight off something like the coronavirus is living a healthy lifestyle where a strong body and immune system can create a barrier to many different infections.

To promote a strong immune system, we must maintain a healthy diet and lifestyle. An exercise regimen that combines cardio and strengthening as well as a healthy diet is an integral part to promoting a strong immune system.

A diet rich in fruits, vegetables, and healthy fats while avoiding processed non-nutritious foods creates an immune system ready for whatever the world throws at us and allows our bodies to be protected from these aggressive viruses.

A treatment to consider that you may not have heard of is intravenous dosages of immune system boosting vitamins. Supplements such as vitamin C, echinacea, elderberry, and garlic are all beneficial nutrients to help fight off an infection. However, many of them are limited due to dosing restrictions and absorption ability.

When you do an IV of vitamin C, zinc and selenium, these nutrients get absorbed right into the blood stream and provide maximum immune system benefits and protection both treating and preventing many infections.

So as the world grows more concerned about the coronavirus, the best defense against this new disease is to adhere to a healthy lifestyle and build up our immune systems to fight off any attempt by the virus to attack the body.

Seeing a naturopathic physician is a great way to start protecting your health!

To find a naturopathic doctor near you, please go to http://www.aznma.org.

Editors Note: Dr. Steven Katz, NMD is a Scottsdale-based naturopathic doctor, and president of AZNMA.

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Four Questions: The Parasite in Your Cat Box – UANews

Friday, February 21st, 2020

Among the many health tips for expectant moms: Pregnant women shouldn't clean up the litter box. But why not? A common parasite called Toxoplasma gondii is to blame. Although the parasite, which can be found in cat feces, is relatively harmless to people with healthy immune systems, those who are immunocompromised including developing fetuses can suffer serious consequences from an infection by Toxoplasma gondii.

On National Love Your Pet Day, Oscar Mendez, a doctoral candidate in neuroscience at the University of Arizona and self-proclaimed cat lover, discusses the "cat litter parasite" and what his research might help us better understand about it. Mendez studies how the parasite affects neurons in the mammalian brain in the Koshy Lab, a laboratory in the university's BIO5 Institute led by neurologist and immunobiologist Anita Koshy.

Q: What is Toxoplasma gondii?

A: Toxoplasma gondii is a common parasite that lives in a host cell to survive. Toxoplasma naturally infects a wide range of warm-blooded animals including birds, rodents and even humans. Infection usually arises from consuming contaminated food or water. The previously listed hosts are known as intermediate hosts, hosts in which Toxoplasma can only reproduce asexually. Felines, including domestic cats, are the definitive hosts of Toxoplasma. In the gut of cats, Toxoplasma can undergo sexual reproduction. The first time a cat is infected, it can poop out millions of infectious forms of Toxoplasma. One unique characteristic of Toxoplasma is that in some hosts, including humans and rodents, the parasite establishes a chronic infection of neurons in the central nervous system, or CNS. Unlike other CNS pathogens, this lifelong CNS infection does not seem to be detrimental to the life of the host as long as they have a normal immune system.

Q: What is already known about how it affects humans, and what are you trying to add to that knowledge?

A: Toxoplasma is estimated to chronically infect the CNS of up to one third of humans across the globe. For the most part, if someone has a working immune system, this persistent brain infection does not cause problems. Problems can arise in those with limited immune responses, such as AIDS patients or developing fetuses. We know a lot about the parts of the immune system that are needed to keep Toxoplasma in check, and we even know a little bit about how different cells in the CNS help keep Toxoplasma controlled. But even though we think neurons are the major CNS cell that get infected with Toxoplasma, we still know very little about the Toxoplasma-neuron interaction. My work is focused on understanding how Toxoplasma alters neurons themselves.

Q: Why is it important to understand how Toxoplasma gondii affects neurons specifically?

A: Neurons are the signaling cells of the brain, and if something goes wrong with the neurons, it can affect the brain's ability to function properly. For example, some patients with symptomatic CNS toxoplasmosis have seizures. These seizures have to be coming from abnormal neuron signaling and, from what we know, most would think this abnormal firing is caused by the massive CNS immune response to uncontrolled Toxoplasma. Yet my work suggests that part of the abnormal signaling could come directly from Toxoplasma's effect on single neurons, which no one has studied until now. In other words, the effect of the immune response may be much more localized than we know.

Q: Do cat owners generally have anything to worry about?

A: I always joke that if you are eating the cat litter, you might have to worry. In reality, for the most part, if you are washing your hands after cleaning the litter, you should be fine. Pregnant women and those who have compromised immune systems should be extra careful and consider not being the one to change the litter. I have a cat at home and do not worry about becoming infected with Toxoplasma. Even in a laboratory setting, the chances of infection are quite low.

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The Therapeutic Antibody Revolution – Technology Networks

Friday, February 21st, 2020

A crucial component of our immune system, antibodies are now the most rapidly growing class of approved biopharmaceutical drugs. We explore the past, present and future of therapeutic monoclonal antibodies.In the 1970s, the Nobel-prize winning work of Kolher and Milstein enabled researchers to produce individual or monoclonal antibodies infinitely in culture using hybridoma technology. This key innovation paved the way for the development of therapeutic antibodies.When we have an immune response, we normally generate lots of different antibodies to different parts of a pathogen, says Mark Cragg of the Cancer Research UK Southampton Centre. Monoclonal antibody technology enabled us to just take just a single antibody to a specific antigen and produce it infinitely in culture.In 1986, the Food and Drug Administration (FDA) approved the first therapeutic monoclonal antibody for the prevention of transplant rejection. By the end of 2019, a total of 79 antibody-based drugs were approved to treat a range of autoimmune conditions, infectious diseases and cancers. Many more potentially exciting therapies are also in the pipeline including against HIV or Ebola.With recent advances in antibody engineering technologies helping to further accelerate progress, therapeutic antibodies are set to remain a feature of the drug development landscape for many years to come.

These Y-shaped proteins have a variable binding domain at one end, which recognizes and binds with a specific protein (or antigen) on a pathogen. At the other end, they have a constant region that interacts with other molecules on immune cells to trigger a response. Collectively, our bodys army of antibody-generating cells B cells have the potential to recognize countless antigens.

You can generate an antibody against a specific target molecule and then use it to block or manipulate how that target works, says Cragg.

Traditional hybridoma technologies involved injecting mice with an antigen and then isolating and immortalizing a single B-cell clone to produce a specific antibody.

But when you put this type of antibody into a person, their immune system will invoke an anti-mouse response which can limit their effectiveness and potentially cause serious side effects, explains Cragg.The next generation were chimeric human antibodies, where the mouse antigen-binding region is placed within a human framework.We still use chimeric antibodies as drugs today one of the most successful is rituximab, which is used to treated lymphoma and autoimmune diseases, says Cragg.

Replacing more and more of the mouse antibody regions has led to "humanized" antibodies where the only remaining amino acids of mouse origin are those that make direct contact with the antigen.

But the latest generation of therapeutic monoclonal antibodies are fully human. These are generated either by using mice that have been genetically engineered to carry human antibody genes, or through recombinant display screening technologies that involve inserting a library of human antibody gene sequences into bacteriophage or yeast.

You basically express your antigen and pan across your display library to find one that binds to it, explains Cragg.

A major advantage of this approach for generating a monoclonal antibody is its speed compared to traditional hybridoma technologies: You can go from three to six months to generate an antibody down to only one to two weeks, says Cragg.

Functional evaluation of bsAbs during pharmaceutical development is critical to their success, but this is not without challenges. Existing evaluative methods such as ELISA and SPR are commonly used but are often time consuming. Therefore, there is high demand for a rapid, simple method for the functional assessment of two or more interactions of bispecific therapeutics. In this app note, discover an assay that caters to this demand with a method that is versatile, high-throughput, and low-cost.

But there is a problem with achieving native pairing of the heavy and light chain molecules that make up each antibody. In nature, these genes sit on different chromosomes and the polypeptide chains are only paired after translation. The traditional approach to creating a display library involves collecting the heavy chain genes in one group and the light chain series in another and then randomly combining these together.

Previously, display screens have involved panning random combinations of libraries containing largely non-native pairs in order to find binders, explains DeKosky.These non-native gene pairings can lead to antibodies that arent good enough quality to become effective therapeutics. But newer display platforms maintain the native pairing of human antibodies by physically linking the heavy and light chain genes together.We can use these display libraries to screen millions of natively-paired antibodies to find natural human antibodies that can bind to the antigen in a much faster and more powerful way than hybridoma technology can do, says DeKosky.

Instead of it taking maybe four months to look at 50 or 100 genes, were looking at more like two weeks to look at 50 to 100,000, says DeKosky. So its really changed the way we can understand and mine patient immune responses.

Another game-changer is rapid DNA synthesis, which removes the need to physically identify and recover a gene using PCR.

If you can sequence it, you can synthesize it, clone it and make it, describes DeKosky.

After identifying an antibody, researchers also have the option to carry out genetic engineering to further improve its binding affinity a process known as affinity maturation.

You effectively make random changes to the antibody binding site, put these sequences into a display library and carry out another screen to find the ones that bind more tightly, explains Cragg.6 Steps for Optimizing Recombinant Antibody Expression

Monoclonal antibodies (mAbs) have pioneered discovery and development in biological science and medicine, playing an increasingly important role in research and drug discovery. To meet this rising demand, researchers have developed alternative methods to accelerate antibody production the generation of recombinant antibodies (rAbs), often in mammalian cell lines. In this white paper, discover the steps to optimizing rAb expression.

The next frontier is more of an intellectual or design problem knowing about what you want the drug to achieve in the body and how youre going to do it, says Cragg.For example, cancer researchers are trying to understand more about one of the most important determinants of antibody activity, the efficient interaction with Fc receptors on the surface of immune cells.Were seeing early signs of that with therapeutics that potentiate T cell responses, says DeKosky. And within the coming decades, I think were going to be using antibodies to recruit more and more cells in one way or another into the game.We are also likely to see the development of more bispecific antibodies, which can simultaneously target two different antigens.Theyre more sophisticated as theyre able to bring in more mechanisms all at the same time, comments Cragg.

Within the next 10 years, well have a larger armory of different monoclonal antibodies and a better understanding of which patients to treat with which antibodies and in what combinations, predicts Cragg. In the longer term, we may remove the need to produce antibodies outside the body at all and instead introducing DNA constructs into the patients to make them on-site making it much, much cheaper.

Researchers are increasingly excited about what the future holds for therapeutic antibodies.

I think in some ways were just getting started exploring what these molecules can really do, concludes DeKosky.

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Discovery of gene associated with 20 autoimmune diseases leads to promising drug trials – The Conversation UK

Friday, February 21st, 2020

No matter how many times a day we wash our hands, clean our house or wash our dishes, were still surrounded by bacteria and viruses which can cause illness and disease. So we rely on our immune system to fight off these potential threats constantly. In most people, the immune system operates as an effective - even if not perfect defensive mechanism.

But in some people the immune system may go awry, causing it to perceive parts of the body itself as a threat and attack the bodys own tissues and cells. This is what happens in type 1 diabetes, where the immune system targets cells in the pancreas that make insulin. It also happens in rheumatoid arthritis, when the immune system attacks the lining of the joints. Both of these are examples of autoimmune diseases.

There are more than 80 different autoimmune conditions that affect more than 4 million people in the UK alone. While treatments that reduce autoimmune attacks have been developed, there is still no cure for these diseases. Existing drugs might also not be effective in all patients, and can cause severe side effects. In order to develop better treatments, we need to have a better understanding of how these diseases develop.

Over the past decade, many studies investigating the genetics of autoimmunity have found a common feature: a particular gene, called TYK2. This gene has been associated with at least 20 autoimmune diseases, including multiple sclerosis, type 1 diabetes, rheumatoid arthritis, lupus, and psoriasis.

Since the discovery of this gene, a drug that targets TYK2 has been developed and is showing promise for the treatment of psoriasis, a disease that causes raised, red, scaly patches on the skin. Based on the results, this clinical trial gives hope not only for treating psoriasis, but for the treatment of other autoimmune conditions as well.

TYK2 plays an integral role in regulating how active the immune system is. But key to the effect of TYK2 on autoimmunity is what scientists call gene variants. Every person will have one of several possible variants of the TYK2 gene. These variants are essentially slightly different versions of the gene, which might make the immune system more or less active depending on what variant a person has.

Certain variants that increase activity in the immune system have been found to increase the likelihood that a person will develop an autoimmune disease, while other variants can actually protect against more than 20 different autoimmune diseases. While genetics is only one of many factors which influence whether a person develops autoimmunity, this discovery may be a major help in improving treatments of many autoimmune diseases.

Since a higher level of TYK2 activity results in autoimmunity, a team of researchers tested the use of a drug, called BMS-986165, which inhibits TYK2 function in treating autoimmune conditions. The drug works by reducing the genes activity in the immune system. Promising results were reported when testing the drug both in pre-clinical and clinical settings.

The team first studied the effects of the drug in human blood cells. After having observed the effect of the drug on the cells, they then moved on to animal models to test the effect it had on a whole organism. The drug was shown to protect mice from several different autoimmune diseases, including lupus, which causes long-term inflammation to the skin, joints, and organs. Treatment with the drug reduced the number of attacking immune cells by 50% in some cases.

These promising results follow on from a 2018 study, which successfully trialled the drug for the treatment of psoriasis. The study found 75% of patients showed a reduction in the size of skin lesions and severity by 75%. Of these patients, 25% had complete clearance of lesions.

These studies, in conjunction with the evidence of the role of TYK2 in another 20 autoimmune diseases, suggest a potential for the use of this drug in the treatment of the other conditions as well. Currently, BMS-986165 is under evaluation in clinical trials in patients with Crohns disease, lupus and further trials for psoriasis.

This article is part of a series tied to Medicine made for you, a series by The Anthill podcast on the future of healthcare and how it could soon get a lot more personal. Read more here.

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Discovery of gene associated with 20 autoimmune diseases leads to promising drug trials - The Conversation UK

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