Category Archives: Immunology

Lilly and Scottish university partner to find new therapies for immunological disorders – BioPharma-Reporter.com

The 4.6m (US$6.4m) research alliance is set to last four years. The partners will work across four diseases psoriatic arthritis, rheumatoid arthritis, fibrosis, and vasculitis.

The project will be led by Glasgow Universitys Institute of Infection, Immunity and Inflammation.

The collaboration is aimed at identifying first-in-class therapeutics for people suffering with these conditions.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation, primarily of the small joints of the hands and feet.

RA affects approximately 0.31% of the adult population worldwide, and it is estimated that within 10 years of diagnosis, 40% of people will be unable to stay in full-time work.This has major socio-economic repercussions. In the UK, this costs the NHS on average 700m per year and indirectly costs the UK economy an estimated 8bn per year, according to a release from the university.

Professor Iain McInnes, vice principal at the University of Glasgow, said with the current backdrop of the pandemic it is particularly important that its research continues to focus on discovering new ways to treat patients with other diseases that affect peoples quality-of-life.

Strengthening links with industry is hugely important as we move to translate our research findings into clinical practice which benefits patients.

Professor Carl Goodyear, professor of translational immunology at that university, said the alliance combines Glasgows world-class clinical and translational skills with Lillys therapeutic capabilities and technology platforms for developing novel therapeutics.

This is a highly unique collaboration that is aimed at harnessing not only cross-disease comparison but also intra-disease pathological comparison across different affected tissues. By providing this disease and tissue contextualization it will enable the identification and validation of unique therapeutic targets.

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Lilly and Scottish university partner to find new therapies for immunological disorders - BioPharma-Reporter.com

ImmuneID Launches with $17M Financing to Profile and Modulate Immune Response at Unprecedented Scale and Resolution – BioSpace

Feb. 17, 2021 12:00 UTC

Unlocking precision immunology to treat severe disease

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- ImmuneID, Inc., a precision immunology company employing a proprietary platform to identify and therapeutically target antibody interactions that drive immune diseases, announced a $17M financing led by founding investor Longwood Fund, as well as Arch Venture Partners, Pitango HealthTech, In-Q-Tel, Xfund, and others. The company plans to use this funding to develop therapeutic programs in areas including severe allergy, autoimmunity, oncology, and infectious disease.

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20210217005096/en/

Lea Hachigian (Photo: Business Wire)

High-quality therapeutic target identification has remained a vexing bottleneck in drug discovery, said Stephen Elledge, Ph.D., ImmuneID co-founder, Lasker Award winner, and Gregor Mendel Professor of Genetics and Medicine, Harvard Medical School. The ImmuneID platform, including the VirScan technology, relieves this bottleneck by using its massively parallel, multiplexed, and unbiased approach to provide previously unavailable insight into human immune responses throughout the course of disease progression.

ImmuneIDs platform is a robust, patented, and well-validated system that makes use of next generation sequencing, robotic automation, and artificial intelligence to interrogate and ultimately drug the immune system. The Elledge Lab has optimized the platform through years of intensive research and development resulting in multiple articles in leading journals such as Science and Cell.

ImmuneID is committed to therapeutically leveraging the powerful data we have generated to create new medicines for patients with severe allergies, autoimmune diseases, cancer, and infectious disease, said Longwood Funds Christoph Westphal, M.D., Ph.D., ImmuneID co-founder and Executive Chair. Lea Hachigian, Ph.D., founding CEO of ImmuneID, and Principal, Longwood Fund, added, We are also applying our platform to generate real-time deep insights into public health risks, and other severe diseases.

The power of the VirScan technology was recently highlighted in Shrock et al., Science 10.1126/science.abd4250 (Sept. 29, 2020), in which deep serological profiling of 232 COVID-19 patients and 190 pre-COVID-19 era controls revealed over 800 epitopes in the SARS-CoV-2 proteome, including 10 high-quality epitopes likely recognized by neutralizing antibodies. ImmuneIDs broader platform was employed in Monaco et al., Nat Commun 12, 379 (2021), to identify strong anti-wheat IgE reactivities in wheat allergic individuals and characterize a key wheat epitope that elicits dominant IgE responses among allergic patients, opening the door to targeted therapeutics.

ImmuneIDs Scientific Advisory Board includes co-founder Stephen Elledge, Ph.D.; co-founder H. Benjamin Larman, Ph.D., Assistant Professor Pathology, Johns Hopkins; co-founder Tomasz Kula, Ph.D., Harvard Society of Fellows, Harvard University; and Michael Mina, M.D., Ph.D., Assistant Professor, Epidemiology, Harvard T.H. Chan School of Public Health.

About ImmuneID

ImmuneID is a precision immunology company using its proprietary platform to simultaneously identify and therapeutically target millions of antibody interactions that drive immune diseases. Based on technology developed by scientific founders Stephen Elledge (Harvard), Ben Larman (Johns Hopkins), and Tomasz Kula (Harvard), we are employing our massively parallel, multiplexed, and unbiased systems to develop therapeutics for autoimmunity, severe allergy, oncology and infectious disease. ImmuneID was founded in 2020 by Longwood Fund and is headquartered in Cambridge, MA.

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ImmuneID Launches with $17M Financing to Profile and Modulate Immune Response at Unprecedented Scale and Resolution - BioSpace

When Foreigners Invade, the Body Fights Back. And It Can hurt. – CU Anschutz Today

Ross Kedl, PhD, doesnt mince words when he describes the effects of his COVID-19 vaccine: It packs a wallop, said the University of Colorado School of Medicine professor.

Kedl, who studies vaccines and teaches in the Department of Immunology and Microbiology at the CU Anschutz Medical Campus, took part in a Phase 3 clinical trial for the Moderna vaccine on campus this past summer.

It hit me hard for a day, he said of receiving his second dose, that was obviously not a placebo. I felt like Id been hit by a truck.

But thats a good thing, Kedl and his colleague, Aimee Bernard, PhD, said.

Our immune cells are responding to the components in the vaccine and building an immune army that is actively training to fight and destroy the pathogen. Aimee Bernard, PhD

Soon after clinical trials for COVID-19 vaccines began, the word began spreading that the effects of stimulating an immune response, particularly after the second dose, were sending people to the couch.

It just means its doing its job, the two immunologists say, addressing the widely prevalent misconception that vaccine injection may mean the shot gave them the illness it was designed to prevent.

Our immune cells are responding to the components in the vaccine and building an immune army that is actively training to fight and destroy the pathogen, said Bernard, assistant director for the CU Human Immunology & Immunotherapy Initiative.

Its immunological warfare, and it generally starts right at the injection site, Bernard said of the arm soreness sometimes followed by body aches, fatigue and even fever. These are all signs that the immune system is working, she said.

The same thing happens when people are infected with the actual virus, Kedl said. When you feel lousy with the flu, those flu-like symptoms are actually immune-like symptoms. Fever sets in almost exclusively because of the triggering of the molecule Interleukin-1, he said. And the reason you feel super achy is because of something called interferon, and thats also an immune molecule thats stimulated because of the infection.

When you feel lousy with the flu, those flu-like symptoms

are actually immune-like symptoms. Ross Kedl, PhD

Vaccines prompt the immune system to recognize and respond to a non-harmful form of a pathogen in order to produce memory cells (T- and B-lymphocytes), Bernard said. These memory cells then patrol the body looking for the infectious pathogen they were trained to fight.

When the second dose enters the body, those memory cells are well-armed and ready for attack, initiating an even more robust immune-system response. Feeling sick is a very good sign, Bernard said.

The data for the vaccines being used in the ongoing national rollout suggest about 70% to 80% of people will experience some notable symptoms after the second shot, Kedl said. But in a vaccine setting, the symptoms generally last only 24 to 48 hours, unlike with a real infection which, in COVID-19s case, can take people down for weeks or worse, he said.

Because their immune systems begin tapering off after age 65, older people often have fewer symptoms post-vaccine because of a weaker immune response. But the data seem to indicate they will still have protection, Kedl said.

Even young, healthy people can have different reactions because of different immune systems and different genetics, Bernard said. We are all unique.

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When Foreigners Invade, the Body Fights Back. And It Can hurt. - CU Anschutz Today

New First-Year Biology Seminar Tackles COVID-19, Vaccinations and Pandemic Misinformation – Cornell University The Cornell Daily Sun

As misinformation over COVID-19 vaccine side effects and distribution conspiracy theories continue to flood social media, members of the general public are often left unequipped with the scientific literacy to discern between clickbait headlines and reliable information.

But Prof. Elizabeth Rhoades, microbiology and immunology, is trying to change that.

A researcher and lecturer, Rhoades jumped on the opportunity to mold a more science-informed student body by crafting a new first-year seminar course: Biology 1250: Keep Calm and Be Science Literate in the Pandemic.

As science is politicized and misinformation continues to spread through social media feeds like wildfire, the class teaches students how to ask questions, find reputable sources and make informed decisions and how dangerous it can be when that doesnt happen, Rhoades explained.

How can you distinguish pseudoscience from real science? How can you make well-informed decisions about your health if you dont know immunology? The answer is that you become science literate, the course description reads.

Targeted toward first-year students regardless of their science background, Rhoades is offering this one-credit course in-person during the second half of the semester. Rhoades explained that the course is structured around class discussions and hands-on activities, and will equip students with the tools to distinguish fact from fiction.

I want to teach [my students] how to go find real news, and how you can tell its not fake, Rhoades said. They will learn how to check if the source has any biases or gains, and how to be skeptical when they consider certain sources.

Rhoades said the course will first provide students with a foundational knowledge of the immunology behind the COVID-19 pandemic, as well as how the vaccine can trigger the bodys defense against infection.

According to the course syllabus, students who take this class will be able to evaluate popular scientific claims, explain the biology behind vaccines and COVID-19 tests and engage in productive conversations around sociocultural issues of the pandemic such as healthcare disparities.

Then, the class will shift toward dissecting the social implications of the virus, as well as misinformation across social media and fraudulent news sites.

Students will also gain hands-on experience navigating scientific rhetoric. For one assignment, students will either take the stance of a COVID-19 vaccine skeptic or believer and analyze each sides argument for the impact the vaccine could have on the long-term health of individuals.

This type of exercise highlights the technique of gathering and applying information, and more importantly, it may open students eyes to different perspectives, Rhoades said. I want students to learn enough about vaccines and where to find information about them, so they can make informed decisions if a vaccine is a good decision for them or not.

According to Rhoades, the experience of this class will have a multiplying effect on generating a more scientifically literate public, as students can have informed discussions on vaccine safety with their friends and family.

Ultimately, Rhoades said she hopes the course will empower students with the critical thinking skills that will allow them to draw their own conclusions on scientific issues, even if they dont have extensive knowledge of science.

You dont have to be a science expert to make science decisions, but I want to teach students to track down the facts online when reading the news, and to be able to make educated choices for themselves, Rhoades said. I see this as science communication at its best.

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New First-Year Biology Seminar Tackles COVID-19, Vaccinations and Pandemic Misinformation - Cornell University The Cornell Daily Sun

Major 2.2m research project aims to improve treatment and understanding of Long COVID – University of Birmingham

Approximately 1 in 10 people with COVID-19 continue to experience symptoms and impaired quality of life beyond 12 weeks

The University of Birmingham today launches a major new 2.2m government-funded research project to improve the treatment, causes and symptoms of so-called Long COVID in non-hospitalised patients.

The two-year project, funded through the National Institute for Health Research (NIHR) and UK Research and Innovation (UKRI), follows a UK-wide joint research call to fund ambitious and comprehensive Long COVID research.

Approximately 1 in 10 people with COVID-19 continue to experience symptoms and impaired quality of life beyond 12 weeks, which is known as Long COVID. Common Long COVID symptoms include, extreme tiredness, shortness of breath, chest pain or tightness, brain fog, insomnia, heart palpitations, dizziness, pins and needles, joint pain, depression, anxiety, tinnitus, earaches, nausea, diarrhoea, stomach aches, loss of appetite, a high temperature, cough, headaches, sore throat, and changes to sense of smell or taste.

Through a partnership with the Clinical Practice Research Datalink using electronic GP records, the University of Birmingham-led team will identify and recruit thousands of non-hospitalised patients with Long COVID who have had symptoms for 12 weeks or longer to a major clinical digital study.

At the heart of the study will be the use of a digital platform, called Atom5 from med-tech company Aparito Limited, which will be configured for the study by experts from the University of Birmingham with patient input. Participating patients will be given access to the digital platform, allowing them to self-report symptoms, quality of life and work capability.

Asub group of patients will receive blood and other biological tests to understand the immunology of Long COVID, and will wear a device that will measure their heart rate, oxygen saturation, step count and sleep quality.

Using their findings, the researchers will co-produce with patients a targeted intervention for Long COVID, tailored to individual patient need. Delivered remotely in the community, via the Atom5TM app, it will provide critical support and information to empower patients in self-managing long COVID. In addition, they will provide tailored resources to support symptom management and nurse-led support for those with the severest symptoms.

The researchers will also use the digital platform to assess whether the treatments and supportive interventions reduce symptoms, improve quality of life, and are good value for money.

All data gathered will be used to help the scientists characterise the symptoms, health impacts, and underlying causes of Long COVID syndromes in non-hospitalised patients providing invaluable insight not currently available.

Principal Investigator Dr Shamil Haroon, Clinical Lecturer in Primary Care at the University of Birmingham, said: Individuals with Long COVID frequently report experiencing diverse physical and psychological symptoms beyond 12 weeks that can be extremely debilitating.

People living with Long COVID have indicated that they feel abandoned and dismissed by healthcare providers, and receive limited or conflicting advice.

Meanwhile, neither the biological or immunological mechanisms of Long COVID, nor the rationale for why certain people are more susceptible to these effects, are yet clear, limiting development of therapies. Its essential we act quickly to address these issues.

Co-Principal Investigator Melanie Calvert, Professor of Outcomes Methodology and NIHR Senior Investigator at the University of Birmingham, added: A large number of individuals that have had COVID-19 experience long-term effects on their health and well-being.

Our study aims to reduce their symptom burden and improve quality of life. Ultimately, people want to be able to enjoy life again and spend time with their friends and family.

It is clear that there is an urgent need for research to help explain the causes that drive the longer-term health effects of COVID-19 so that we can optimise patient care.

Our digital trial platform in primary care will not only facilitate research exploring the underlying cause of Long COVID, but also the evaluation and co-production of suitable interventions.

Health and Social Care Secretary, Matt Hancock, said: I am acutely aware of the lasting and debilitating impact Long COVID can have on people of all ages, irrespective of the extent of the initial symptoms.

Fatigue, headaches and breathlessness can affect people for months after their COVID-19 infection regardless of whether they required hospital admission initially.

In order to effectively help these individuals we need to better understand long COVID and identify therapeutics that can help recovery. This funding will kick-start ambitious projects to do just that.

Chief Medical Officer for England and Head of the NIHR, Professor Chris Whitty, said: Good research is absolutely pivotal in understanding, diagnosing and then treating any illness, to ease symptoms and ultimately improve lives.

This research, jointly funded through the NIHR and UKRI, will increase our knowledge of how and why the virus causes some people to suffer long term effects following a COVID-19 infection - and will be an important tool in developing more effective treatments for patients.

Health Minister, Lord Bethell, said:The UK is at the forefront of scientific research and innovation when it comes to the treatment of COVID-19. This work is vital in helping us to build on our knowledge and improve the treatment of the longer-term impacts of the virus.

This research will make the best use of available evidence to help us identify the causes, the consequences and most importantly the best treatments to help people recover from COVID-19 in the long term.

The University of Birmingham-led project will include a Lived Experience Advisory Panel (LEAP), made up of a group of long COVID patients, who will work with researchers and clinicians to develop the research from a patient perspective. LEAP member and long COVID patient Dave Stanton, aged 74, welcomed the research.

The RAF veteran said: COVID-19 has knocked me sideways, with a long and debilitating battle since initially becoming ill in March last year, including having to have surgery to replace my pacemaker following additional damage the virus has caused to my heart.

"Each day is baby steps in terms of recovery, but almost one year on I am still battling a myriad of symptoms from memory loss to difficulties breathing, pins and needles, and immobility.

"I am delighted to be part of this research project, which will give hope to so many out there who are, like me, struggling with the longer term crippling effects of this virus.

The research team consists of multi-disciplinary experts heavily involved in COVID-19 research from the University of Birmingham, including Dr Krish Nirantharakumar, Dr Joht Singh Chandan, Dr Olalekan Lee Aiyegbusi, Professor Janet Lord, Professor David Wraith, Professor Alastair Denniston, Dr Sarah Hughes, Dr Louise Jackson, Dr Grace Turner, Dr Samantha Cruz Rivera, Dr Anuradhaa Subramanian, Professor Georgios Gkoutos, Professor Elizabeth Sapey, Professor Tom Marshall, Dr Christel McMullan, and Professor Steven Marwaha.

It also includes Dr Puja Myles and Dr Tim Williams, of the Medicines and Healthcare products Regulatory Agency (MHRA), and Dr Elin Haf Davies, of Aparito Limited.

Project partners will include patient campaign group LongCovidSOS, the National Institute for Health and Care Excellence (NICE), the UK Coronavirus Immunology Consortium (UK-CIC), and the Post-hospitalisation COVID-19 Study Consortium (PHOSP-COVID). Long COVID patients and their carers have co-developed the research plan, including COVID-19 survivor Gary Price who will also act as a co-investigator.

For more information, please contact Emma McKinney, Communications Manager, University of Birmingham, on +44 7815607157. Alternatively, contact the Press Office out of hours on +44 (0)7789 921165.

Notes to Editors

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Major 2.2m research project aims to improve treatment and understanding of Long COVID - University of Birmingham

From astronomy to immunology, it’s time to restore confidence in evidence-based science – Salon

The widespread availability of an FDA-approved vaccine for COVID-19 will not ensure its consumption by the public. This is reflective of a broad cultural problem there is a deep undercurrent of mistrust, especially of elites, running through American society today but it also echoes a cultural problem in the world of science, specifically.

Americans of all stripes have come to regard scientists as part of the elite, in part because they have sequestered themselves in an ivory tower, saturated with ambition for academic honors and consumed with sterile intellectual gymnastics. Much of current scientific culture focuses on nuances whose sole purpose is to garner their researchers higher academic status by impressing colleagues, rather than serving the public's interest or carrying any practical relevance for our daily life.

This state of affairs is particularly apparent in my field: the world of physics. For instance, in theoretical physics, a phalanx of untestable notionsabout the multiverse, hypothesized extra dimensions, the idea that we live in a simulation, and the argument that there is no need for experimental evidence to justify the string theory strategy in unifying quantum mechanics and gravityoccupy centerstage. At the same time, there is a taboo on an open discussion of certain common-sense questions, such as whether there are other intelligent civilizations in outer space and whether our civilization is the smartest kid on the galactic block.

"The surest way to corrupt a youth is to instruct him to hold in higher esteem those who think alike than those who think differently", wrote the philosopher Friedrich Nietzsche in his book "The Dawn of Day," published in 1881. And indeed, the psychological pressure on physicists to conform with fashionable trends promotes a herd mentality in which young scientists today feel obligated to work on far-fetched ideas promoted by senior colleagues just in order to secure jobs, thereby perpetuating the problem. These young scientists learn from the examples set by their elders, who often react to original thought with violent pushback and bullying. I know, because I have been the subject of such assaults.

When the first interstellar object, 'Oumuamua, was glimpsed passing through our solar system in October of 2017, scientists quickly agreed that it was weird on half-a-dozen counts: it had a flattened shape with extreme proportions never seen before among comets or asteroids, an unusual initial velocity, and a shiny appearance; it lacked a cometary tail, but nevertheless it exhibited a push away from the Sun not explainable by gravity. However, despite these anomalies, the mainstream scientific community immediately declared business as usual and decreed the object to have been an unusual asteroid or cometalbeit one that was unlike any asteroid or comet seen before. The response brought to mind a kid who has encountered many cats at home and, upon visiting the zoo and seeing an elephant, simply assumes it to be an unusual cat. Such naivete is charming in a child; it is less tolerable in a scientist.

We ought to hold ourselves to a higher standard, I felt so several months after 'Oumuamua was first sighted, I suggested that its weirdness may imply that it was a product of an alien technology, possibly a thin sail pushed by sunlight. (Our own civilization has dreamed of such a perfect spacefaring technology for decades, and I had recently helped to design a prototype of one for the Breakthrough Starshot Initiative, an effortsupported by earthbound innovators and dreamers such as Yuri Milnerto reach our closest neighboring star within our lifetimes.)

In fact, another object showing evidence for push by sunlight with no cometary tail was discovered in September 2020 by Pan STARRS. It was initially given an astronomical label, 2020 SO, before it was identified as a stray rocket booster from a 1966 mission to the Moon that is still bound to the Sun. 'Oumuamua moved much fasteron an escaping trajectory from the Sun, implying that it must have originated from interstellar space.

When I spend time on vacation near a beach, I enjoy studying natural seashells but every so often I encounter a plastic bottle which is artificially made. Whatever its purpose, if artificial in origin, 'Oumuamua would represent "a message in a bottle": the first evidence that we are not alone.

I first articulated this hypothesis in a commentary that I published in Scientific American; I subsequently quantified it in a scientific paper with my postdoc, Shmuel Bialy. Although far from the most speculative thing I have ever published indeed, in comparison to some of my research on dark matter, the paper was rather tame it generated quite a fuss. It was accepted for publication within a few days of its submission to The Astrophysical Journal Letters. It became the only paper I know of to have been quoted verbatim on both CNN and Fox News, and to have inspired a new brand of wine ("Cuve 'Oumuamua" by Bonny Doon). And judging by my inbox, it has stirred a great deal of interest in people far beyond the rarefied halls of academia.

But my idea also generated an impulsive pushback within the scientific mainstream. Some scientists expressed a strong opinion on Twitter based on prejudice without studying the evidence. It would have been better if they had followed the advice of basketball coaches: "keep your eyes on the ball and not the audience". After all, by siding with the mainstream during Galileo Galillei's days, we wouldhave given justification to placing him in house arrest rather than looking through his telescope. This would clearly be in contradiction to our current support of evidence-based science.Reality does not go away if you ignore it.

At the same time that conservative scientists argue for "business as usual" regarding 'Oumuamua, other reputable scientists admit that the object is weird and suggest "never seen before" explanations for it each of which requires an imaginative leap much greater than the one necessitated by the lightsail hypothesis. For example, a recent suggestion was that 'Oumuamua may be a hydrogen iceberg, but this explanation faces the problem that such an object is likely to evaporate during its long interstellar journey. Another recent proposal, that it is an elongated fragment from the gravitational disruption of a bigger object by a star, faces the shortcoming that such disruptions are rare and that 'Oumuamua's shape was inferred to be pancake-like based on its light curve. Another suggestion, that 'Oumuamua is pushed by sunlight because it is a porous dust bunny which is a hundred times less dense than air, raises severe doubts about its ability to survive through a tumultuous interstellar trip for millions of years.

The mainstream orthodoxy contradicts itself by claiming that 'Oumuamua is not unusual and at the same time endorsing these notions that it could be explained by "never-seen-before" natural mechanisms. One cannot escape the impression that these exotic explanations are promoted simply to avoid a discussion on the possibility that 'Oumuamua might be of artificial origin.

Why is the study of alternative explanations for the anomalies of 'Oumuamua any different from the search for radical explanations for possible anomalies (involving cores instead of cusps in the centers of galaxies or unusually cold hydrogen during the cosmic dark ages) tied to the unknown nature of the dark matter? Given that between a quarter and half of all stars we examined host an Earth-like planet with a surface temperature that can support liquid water and the chemistry of life-as-we-know-it, the proposition that we are not alone is rather conservative, and should have been endorsed by the mainstream by now. Yet our scientistsand our elected leaderswould prefer not to look under this particular rock. In 1993, Congress halted federal funding to the Search for Extraterrestrial Intelligence (SETI), even though only a tiny fraction of all possible technological signatures of extraterrestrial civilizations had been searched for at that point. Territories that remain unexplored today include industrial pollution of planetary atmospheres, artificial lights, solar cells or mega-structures in space.

It seems obvious to me that space archaeology a burgeoning field of research concerned with the search for extraterrestrial technological relics should be funded as generously as the search for, say, the faddish Weakly Interacting Massive Particles (WIMPs), which were thought to be the constituents of dark matter. The physicists Guiseppe Cocconi and Philips Morrison wrote of SETI in 1959: "The probability for success is difficult to estimate, but if we never search, the chance of success is zero."To that I would add: when you are not ready to find exceptional things, you will never discover them.

Yet my colleagues at the forefront of the search for extraterrestrial intelligence seem to have forgotten this fundamental scientific principle. In contrast to its cool reception in the scientific community, SETI hits a nerve in the general public. There lies a paradox: the public pays taxes that support science and is more eager to know the answer to the question: "are we alone?" than: "are WIMPs the dark matter?", not to speak about supporting speculative notions of "extra dimensions" or the "multiverse", which have no reality check to their credit.

Ironically, indeed, the reason that physicists enjoy freedom is that their blue-sky mainstream used had practical impact. The stable funding of physics stemmed from Vannevar Bush's vision of "The Endless Frontier" after the demonstrated relevance of the Manhattan Project to society. Why would the mainstream scientific community shy away from the public's interests and focus on esoteric questions that have little relevance to the layperson? Are scientists supposed to hide behind the opaque technical walls of a self-sustained bubble and ignore the public that funds their research?

Previous generations of physicists understood that when evidence is incomplete, we have to live with scientific uncertainty and consider multiple interpretations of the available data. I fear that physicists today, like their oft-disparaged counterparts in the SETI community, have forgotten this important principle. Nowhere in science is this failure clearer, in my opinion, than in the scientific community's response to the half-dozen anomalies displayed by the first interstellar object that we have discovered.

A scientist must go where the evidence isbut too often, our scientists do not. I do have hope for the future, however. My optimism stems from raising my young daughters, who have no inhibitions in exploring the truth; this is why they learned so much over the short term of their childhood. Perhaps scientists should behave more like kids. Mistakes are an inevitable part of our learning experience as students of mother nature, humbled by the fact that its splendor often exceeds our imagination.

I am practicing what I preach by preparing to confront my own mistakes. Starting in 2023 the Legacy Survey of Space and Time (LSST) on the Vera C. Rubin Observatory will survey the sky for new objects. If we find another weird object like 'Oumuamua on its way towards us, we could send a spacecraft to take a close-up photo of it and identify its nature. Let my hypothesis about 'Oumuamua be judged according to the evidence from this research, rather than by the popularity contest that guides so much of modern science.

Science is a never-ending work in progress. We show integrity by entertaining multiple possible interpretations of evidence to the public. The new generation of innovators should not be held hostage by the mistakes of the past. After standing in line at the bank, I never hear the cashier saying that I am not allowed to cash my check because the customer ahead of me had an overdraft. We should examine each case based on its own merit.

Scientists could regain the public's trust by being straightforward about the inevitable roller-coaster of trial and error associated with innovation whether it be the search for a vaccine for COVID-19 or the search for technological signatures of other civilizations. Rather than pretending to know the outcome in advance, we should admit what we do not know and study all possible interpretations, so that the public will believe our robust conclusions when new evidence brings clarity.

On December 18, 2020, The Guardian published a report about a tantalizing radio signal that was detected within the Breakthrough Listen project by the Parkes telescope in Australia from the nearest star to the Sun, Proxima Centauri. This dwarf star hosts an Earth-size planet, Proxima b, in its habitable zone where liquid water could allow the chemistry of life on the planet's surface. There is no scientific paper accompanying the report and therefore it's too early to draw any inferences. Astronomers must verify that the signal cannot originate from radio interference on Earth or some natural emission mechanism. Terrestrial interference should be different for telescopes at different locations on Earth. If the radio source repeats and resides on Proxima b, then it should show an 11 days modulation associated with the planet's orbital (and spin) period. As soon as I saw the news report, I wrote to the publisher of my forthcoming book: "We might have friends out there. Better than a five star review is getting reassurance for the book's content from an actual star in the sky".

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From astronomy to immunology, it's time to restore confidence in evidence-based science - Salon

Duke Immunology

The immune system defends us against infection and provides surveillance against tissue damage and cancer. Studies of the immune system are therefore essential to understanding and treating a myriad of diseases. Exciting discoveries in immunology promise, and are delivering, better vaccines to protect against infection, new approaches to suppress allergy, inflammation, autoimmunity and transplant rejection, and new tools to attack cancer.

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What we know about Covid reinfection, immunity and vaccines – The Guardian

How long does natural protection from a first infection last?

There is no clearcut answer to this, but several studies suggest protection generated by a previous infection lasts for at least a few months.

According to one preprint study from Public Health England (PHE) released in January, which looked at hospital staff, the median interval between the first infection and reinfection was more than 160 days about five months. Meanwhile, a study from Qatar suggests protection by natural immunity of about 95% efficacy lasts about seven months.

Again, that is unclear. Different people will react differently to reinfection, depending on how their immune responses reacted to the first infection, probably, says Julian Tang, a clinical virologist and honorary associate professor in the respiratory sciences department at the University of Leicester.

For some, a second infection is less severe than the first. According to a study from Qatar, less than 0.2% of people tested positive for Covid at least 45 days after their first positive test, with only about a fifth of these showing strong or good evidence for reinfection. Of these 54 people, just one was hospitalised, and even then only with a mild infection.

A second study from Qatar yet to be peer-reviewed supports this, with two-thirds of reinfections only picked up through random or routine testing. Again it suggest reinfection is rare, with just 129 people out of 43,044 followed showing evidence of reinfection over a median of 16.3 weeks.

The PHE study also suggested that reinfection tended to be less severe, with about a third of those who caught Covid for a second time showing symptoms, compared with 78% for first infection.

But there have been a number of cases around the world of reinfection leading to worse disease.

A recent study from researchers in Brazil, about to be published in the Journal of Infection, found that of 33 people thought to have caught Covid for a second time, 12% were hospitalised one of whom died - although none required such care for their first infection.

If you didnt have a good immune response, you could get infected again by exactly the same virus, says Deborah Dunn-Walters, a professor of immunology at the University of Surrey and the chair of the British Society for Immunologys Covid-19 and immunology taskforce.

If that immune response was good, the chances of being reinfected by the same variant will be lower, but reinfection might still occur by other variants.

However, the situation is not black and white as this depends on the mutations a new variant contains, and how they affect the ability of the virus to infect the cell and its interactions with the bodys antibodies and T-cell responses generated by the immune system as a result of the previous infection.

The possibility for a new variant to fuel reinfections has been highlighted by researchers in Brazil: despite about three-quarters of the population of Manaus thought from antibody tests to have been infected with Covid by October, there was a sharp uptick in hospital admissions for Covid in January this year. One explanation, they say, is the emergence of new variants of the coronavirus that may evade immunity gained from earlier infection.

Indeed, research published this week by researchers in Oxford, yet to be peer-reviewed, revealed that people who had recovered from Covid showed T-cell activity towards new variants, including the South African variant. But in general their antibodies were less able to neutralise the Kent and South African variant than the original coronavirus variant, suggesting a potentially lower level of defence.

It appears so, but there are several factors at play. Whether you catch it or not is a combination of whether you have got immunity and whether you have seen [the virus], says Dunn-Walters.

Some people may be at greater risk because of social factors such as occupation, which means they have greater chance of coming into contact with the virus again for example, healthcare workers would be expected to be at greater risk of both infection and reinfection because of this.

But there are also biological factors that might leave some people more at risk of catching Covid for a second time. Each human is unique, as are their immune responses, which govern both the risk of reinfection and the severity of these reinfections, so it is very difficult to generalise research findings and clinical trial results to individuals in any population, says Tang.

Vaccination plays a key role in protecting individuals from a first infection. But it is also important for those who have already had Covid. While natural immunity can be gained from a previous infection, jabs give much more certainty over the level of protection produced and boost protection gained from a previous infection.

Vaccines may also offer greater protection against different variants. According to the preprint by Oxford researchers, people who received two doses of the Pfizer/BioNTech jab had a strong T-cell and antibody response against the original coronavirus and the Kent and South African variants, suggesting the vaccine probably offered protection against infection for all of these variants. That contrasts with the findings for those who had only previously had a natural infection.

Natural infection doesnt guarantee you immunity as well as perhaps the vaccination might, says Dunn-Walters.

While studies have suggested that some other Covid vaccines may be less effective against the South African variant than against the original or Kent variants of the coronavirus, experts say these jabs still offer good levels of protection against serious disease. Whats more, vaccines are being tweaked to better target new variants, a move that will also bolster protection.

This article was amended on 13 February 2021. The original incorrectly stated that a study about to be published in the Journal of Infection found that of 33 people thought to have caught Covid for a second time, one died, and 12 were hospitalised. It was actually 12.1% (four people) of the 33 who needed treatment in hospital.

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What we know about Covid reinfection, immunity and vaccines - The Guardian

Second COVID Shot Packs the Big Punch – MedPage Today

Like scores of other physicians and healthcare workers, T.J. Maltese, DO, a neurologist in private practice on Long Island in New York state, had no problem with his first dose of the Moderna coronavirus vaccine -- but he was knocked out by the second.

Maltese got his second shot at 4:30 p.m. on a Friday. Within 2 hours his arm was sore. He developed flu-like symptoms overnight, and had chills and body aches on Saturday. His low-grade fever (peaking at 101.4F) lingered all day. If he had to work, he could have pushed through, he said, but he rode out his symptoms on his couch with the help of the occasional Tylenol.

By 9 p.m. Saturday, Maltese started to feel better. He got a good night's sleep and was back to normal on Sunday.

"I know plenty of people with minimal symptoms after the second dose, so it's not definite you'll feel side effects," he wrote in a Facebook post. "But be prepared for the possibility."

The healthcare worker scuttlebutt is that the second dose of any COVID-19 vaccine packs a punch -- unless you've already had COVID, then the first dose can hit just as hard.

These perceptions are substantiated by immunology and by data from the vaccines' phase III trials, and some hospitals have even altered their healthcare worker scheduling in anticipation of second-dose side effects.

Priming the Immune System

Immunologists and infectious disease experts interviewed by MedPage Today said it's not unexpected that second-dose reactions are more intense than the first.

"The first time the immune system comes into contact with something, it's getting primed," said Purvi Parikh, MD, an immunologist at NYU Langone Health in New York City. "That goes for everything, from vaccines to allergies. It's rare on the first time to have a strong reaction. After that, the immune system recognizes it, so you have a much stronger reaction."

"We saw it in the trials, so it's really not surprising," Parikh added. "Now we're seeing it in real time as the vaccines are being rolled out."

In both Pfizer's and Moderna's phase III trial data, systemic adverse events were reported more frequently after dose 2 than dose 1. For the latter, rates were 54.9% versus 42.2% for placebo after the first dose and 79.4% versus 36.5% for placebo after the second dose. Fever, headache, fatigue, myalgia, arthralgia, and chills were far more common after the second dose compared with the first dose and with all placebo doses.

Stanley Weiss, MD, an infectious disease specialist and epidemiologist at Rutgers New Jersey Medical School, said since his institution served as a site for the Moderna trial, the primary investigator was able to give faculty and administrators an early update on what to expect following vaccination.

"They said there was a very high rate of fatigue after the second dose, so we encouraged administrators ... to figure that many healthcare workers getting the vaccine might not be well enough to work the day after the second dose," Weiss told MedPage Today.

Weiss added that administrators were also careful not to vaccinate staff from within the same unit -- an ICU team, for instance -- on the same day.

Fewer Problems for Older Patients?

Both Weiss and Parikh said they had a far stronger response to the second dose of the Moderna and Pfizer vaccines, respectively. Weiss had fatigue and a severe headache for 2 days. Parikh's chills, fatigue, and headache resolved within 24 to 36 hours.

Zubin Damania, MD, a.k.a. ZDoggMD, said the second dose of his Moderna vaccine knocked him out: "I couldn't sleep, I had a fever, rigors, body aches, a headache -- full-on man-flu," he joked on a recent episode of his show.

His guest for that show was vaccine expert Paul Offit, MD, who also had fever and fatigue for about 48 hours after the second dose of the Pfizer vaccine.

"That reaction is less common in people over 65, and I'm over 65, so I'm thinking I'm not going to suffer that, but I did," Offit said.

Indeed, older patients are thought to have less of a reaction due to typical weakening of the immune system as people age, Parikh said: "The idea is that their immune system is not as robust as a young person's."

Dose 1 Rougher for Those with Previous COVID

Parikh said the same immunological concept behind a stronger response to the second dose also applies to first-dose effects for those who've had COVID-19 before.

"It's the same reason why some people who've had COVID and recovered get these effects with the first shot sometimes. The immune system has seen it before," she said.

Victoria Arthur, MD, of Lexington Pediatrics in Massachusetts, suspects she had COVID in March 2020, but wasn't able to confirm her diagnosis. Still, while all of the other physicians and healthcare staff in her office felt fine after the first dose of the Moderna vaccine, she did not.

"How I felt was how everyone else was describing their second vaccine," Arthur told MedPage Today.

Within three hours of her first dose, she had a headache, neck pain, and cognitive fog. She woke up at 3 a.m. with bad nausea and stomach cramps, and spent the entire next day in bed. By Monday, though, her only lingering symptom was a sore arm.

Her reaction to her second dose was similar, she said. Nonetheless, she was glad for it.

"I'm always grateful when I have a reaction, that means the body is doing its thing," she said. "I'm very fortunate to have been given the vaccine, so any side effect is worth it."

Being appreciative of having been vaccinated, despite the side effects, was a common sentiment among these healthcare professionals.

Weiss said second-dose side effects shouldn't deter anyone from getting vaccinated: "The benefits greatly overwhelm the risk of side effects. It's not a reason to delay."

"I'll take 30 hours of some mild misery," Maltese said, "over days to weeks of much worse -- and more unpredictable -- misery."

Kristina Fiore leads MedPages enterprise & investigative reporting team. Shes been a medical journalist for more than a decade and her work has been recognized by Barlett & Steele, AHCJ, SABEW, and others. Send story tips to k.fiore@medpagetoday.com. Follow

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Second COVID Shot Packs the Big Punch - MedPage Today

STING activation may be a new approach to reduce graft-versus-host disease – News-Medical.net

MUSC Hollings Cancer Center researcher Yongxia Wu, Ph.D., identified a new target molecule in the fight against graft-versus-host disease (GVHD). Bone marrow transplant, a treatment for certain blood cancers, is accompanied by potentially life-threatening GVHD in nearly 50% of patients. A January 2021 paper published in Cellular and Molecular Immunology revealed that activating a molecule called STING may be a new approach to reduce GVHD.

Xue-Zhong Yu, M.D., professor in the Department of Microbiology and Immunology, focuses on understanding the intricate immune mechanisms that regulate GVHD development and anti-tumor activity.

Recently, STING (stimulator of interferon genes) has been highly studied in the context of cancer. Data from other groups has shown that STING activation in T cells helps the immune cells fight cancer. Cancer cells are essentially a "bad" version of the body's own cells and an appropriate target for its immune system. In contrast, in the case of GVHD, T cells fight the body's own "good" cells - in essence, the body attacks itself. Based on the previous data, it seemed logical that high STING activation, though good when it comes to cancer, would be bad in the context of GVHD.

Yu's findings in a mouse model of GVHD confirmed this hypothesis. In the mouse model, which was obtained from collaborator Chih-Chi Andrew Hu, Ph.D., a Wistar Institute professor of Pathology and Laboratory Medicine, GVHD was induced by bone marrow transplant, which closely models the disease development in humans.

To understand how GVHD develops after bone marrow transplantation, one must consider two immune systems: the donor's and the recipient's. The key immune cells are the antigen-presenting cells and the T cells. The immune system knows what to attack based on specific "tags," called antigens, that are shown to the T cells by the specialized antigen-presenting cells. Dendritic cells are the most effective antigen-presenting cells, and they play a critical role in GVHD.

Work from other research groups in cancer has demonstrated that STING signaling can regulate antigen- presenting cell function. STING is an important molecule in a DNA-sensing pathway that results in the production of inflammatory cytokines. But it is not known how STING regulates these cells in the context of GVHD.

The researchers used the mouse models to determine whether GVHD improved or worsened when STING was 1) absent in the donor immune cells, 2) absent in the recipient immune cells and 3) overexpressed in the recipient immune cells. GVHD severity was not changed when STING was absent from the donor immune cells. However, GVHD was more severe and mortality rates were higher when STING was missing from the recipient immune cells.

Yu and collaborators then looked at different cell subsets to try and understand which cells were most impacted by the loss of STING. Surprisingly, STING expression in the recipient mouse's antigen-presenting cells (dendritic cells) reduced donor T cell expansion and migratory ability after bone marrow transplant. In other words, it made it less likely that the T cells of the recipient mouse would attack its "good" cells and lead to GVHD. This finding was confirmed using a pharmacological drug that turned on the STING molecule. Activating STING in the host before transplantation reduced GVHD severity.

The finding in a mouse model that activating STING with a pharmacological drug reduced GVHD could be clinically relevant in that it suggests the possibility that a STING-activating drug might protect bone marrow transplant recipients from GVHD. Much more basic and clinical research will be required to assess that possibility, but Yu's findings suggest that such research is warranted.

To understand why the research team observed what they did, they will continue to unravel the biological functions of the STING molecule. Unanswered questions include what makes STING function differently in different immune cell subsets.

Tools such as the mice from our collaborator allow us to study this more thoroughly. Total-body deletion of a protein does not allow for specific study in cell subsets, and we think that STING must have different roles in different cells."

Xue-Zhong Yu, M.D., Professor, Department of Microbiology and Immunology, MUSC Hollings Cancer Center

Source:

Journal reference:

Wu, Y., et al. (2021) STING negatively regulates allogeneic T-cell responses by constraining antigen-presenting cell function. Cellular & Molecular Immunology. doi.org/10.1038/s41423-020-00611-6.

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STING activation may be a new approach to reduce graft-versus-host disease - News-Medical.net