Tag Archives: prevent

Bengal Government And State Poll Panel Failed To Prevent Violence; Bid To Blame Central Forces Has Sinister Intent – Swarajya

  1. Bengal Government And State Poll Panel Failed To Prevent Violence; Bid To Blame Central Forces Has Sinister Intent Swarajya
  2. Smriti Irani Slams Congress Alliance With Mamata As Bengal Panchayat Election Violence Escalates India Today
  3. 18 Deaths, Rampant Malpractice: Bengal’s Panchayat Elections Turn Bloody Once Again The Wire
  4. Violence Continues In Bengal, Several Areas To Vote Again & Other Headlines | News Wrap @ 8 AM Hindustan Times
  5. BJP alleges central forces deliberately not deployed in West Bengal panchayat polls Firstpost
  6. View Full Coverage on Google News

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CMA’s appalling stalling can’t prevent courtroom disaster, reinforces ‘closed for business’ narrative — Justice Marcus Smith moves forward swiftly and is unconvinced of agency’s market definition – FOSS Patents

  1. CMA’s appalling stalling can’t prevent courtroom disaster, reinforces ‘closed for business’ narrative — Justice Marcus Smith moves forward swiftly and is unconvinced of agency’s market definition FOSS Patents
  2. Microsoft Appeal Against UK Block of Activision Blizzard Deal to Start July 24 – News VGChartz
  3. Microsoft pledges to be ‘determined’ and ‘creative’ to get ATVI merger clearance TweakTown
  4. Microsoft’s Activision Blizzard gamble faces regulatory battle FOX 5 Washington DC
  5. Microsoft Activison merger “unconditionally cleared” WePC – PC Tech & PC Gaming News
  6. View Full Coverage on Google News

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Effectiveness of a bivalent mRNA vaccine booster dose to prevent severe COVID-19 outcomes: a retrospective cohort study – The Lancet

  1. Effectiveness of a bivalent mRNA vaccine booster dose to prevent severe COVID-19 outcomes: a retrospective cohort study The Lancet
  2. Bivalent COVID-19 booster vaccine shown to be highly effective in reducing deaths and hospitalizations Medical Xpress
  3. Durability of Bivalent Boosters against Omicron Subvariants | NEJM nejm.org
  4. Pfizer bivalent vaccine reduces Covid-related death risk by 68 per cent in older people: Study The Financial Express
  5. New bivalent booster vaccines highly effective in reducing Covid deaths and hospitalisations, study finds Independent.ie
  6. View Full Coverage on Google News

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Russia Moves to Digitize Military Summons, Prevent Conscripts from Fleeing Amid Fears of New Draft – The Moscow Times

  1. Russia Moves to Digitize Military Summons, Prevent Conscripts from Fleeing Amid Fears of New Draft The Moscow Times
  2. Russia to soon introduce electronic call-up papers in crackdown on draft dodgers after parliament vote Reuters
  3. Russia Moves to Block the Exits for Future Cannon Fodder The Daily Beast
  4. Russia moves to tighten conscription law, pressing more men to fight The Washington Post
  5. Russian State Duma introduces legislation to ban citizens from leaving country from moment they receive summons (including electronically) Meduza
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Could taking a depression pill prevent lasting agony of shingles?

Sitting in A&E, with piercing pain radiating across his forehead and his left eye, David Hadfield clutched his head, struggling to work out what was going wrong.

The answer emerged during his hour-long wait at Manchester Eye Hospital. A ‘bumpy, burning rash’ began to develop down one side of his forehead, just above his left eye and eyebrow, a symptom which immediately ‘gave the game away’ to doctors examining him: he had shingles.

‘I was absolutely astounded,’ says David, 76, who lives in Alderley Edge in Cheshire. ‘I didn’t know much about the condition, but I certainly didn’t think it could affect your face or eyes. It came out of nowhere.’

Four months on — six weeks of which was spent in a darkened room to prevent light aggravating his sensitive eye — David was still in agony and relying on large doses of powerful painkillers.

Professor Pickering and other researchers are launching a major trial — the Athena Shingles Study — treating newly diagnosed cases with amitriptyline (a type of antidepressant) 

‘You’d think that when the rash goes, which it did after about ten days, the pain would go away, too,’ says David.

‘But it has just carried on and on. There were days when I thought my eye socket was on fire because the pain was so bad. You start to think: will it ever go away?’

Shingles is a common infection caused by the reactivation of varicella zoster, the virus that triggers chickenpox. It can lie dormant in the body for years, but if your immune system is compromised the virus can escape, travelling along nerves to the skin, producing the signature blister-like rash.

While the visible signs of the virus tend to clear within a week or so, around 14 per cent of patients are left with severe nerve pain, known as post-herpetic neuralgia, which can last for up to a year and may even become permanent.

‘The problem is that there aren’t any good treatments for shingles pain,’ explains Tony Pickering, a professor of neuroscience and anaesthesia at Bristol University.

‘And, unfortunately, I have seen patients who even 20 years down the line are still suffering with some kind of pain.’

It’s why Professor Pickering and other researchers at Bristol, Oxford, Southampton and Warwick universities, are launching a major trial — the Athena Shingles Study — treating newly diagnosed cases with amitriptyline (a type of antidepressant that at lower doses is used to treat nerve pain) to try to prevent post-herpetic neuralgia.

A small study in 1997 suggested taking amitriptyline early may help, but the researchers say this new study will be the largest on the subject.

For 80 per cent of those who catch chickenpox, the virus resides in the body without causing problems, explains Dr Ashish Gulve, a consultant in pain medicine at The James Cook University Hospital in Middlesbrough and medical advisor to the Shingles Support Society.

‘However, in some people, perhaps decades later, the virus is reactivated, possibly because of advancing age — shingles is most common in the over-70s — or due to a compromised immune system which makes it harder to fight infection.’

Diseases and treatments that weaken the immune system, such as type 2 diabetes and chemotherapy, can also allow the virus to become active.

(Being exposed to chickenpox again shouldn’t be a risk. In fact, research published in the BMJ in 2020 found that adults exposed to a child with chickenpox are around 30 per cent less likely to develop shingles for up to 20 years, possibly because re-exposure to the virus boosts immunity to shingles.)

A small study in 1997 suggested taking amitriptyline early may help, but the researchers say this new study will be the largest on the subject

Shingles can appear in any nerve in the body and, once the virus is reactivated, the affected nerve starts sending pain signals even if there is no rash.

‘The hypersensitivity can be so acute that some patients can’t even touch the affected area,’ says Dr Gulve. ‘Even a cold breeze can set off pain.’

David’s problem began when he woke one morning with a headache unlike any he’d had before. Two days of taking ibuprofen had no effect and he soon felt an agonising, burning pain around his left eye.

After his diagnosis, David, a former business executive, was prescribed gabapentin, which is a medication used to treat nerve pain, as well as antivirals.

David’s vision was unaffected, but the pain in his eye, forehead and eye socket was ‘terrible’.

‘I’m a very busy and sociable person, but overnight I became someone who had to sit at home with the curtains closed all day, covering my bad eye with my hand as a way of trying to head off this awful pain,’ he says.

‘It literally felt like my eye and my forehead were burning. It also felt like something was sticking in my eye, which had become bulbous and swollen.’

At one point, David was taking 18 tablets a day.

Professor Pickering says ‘throwing the kitchen sink’ at post-herpetic neuralgia may not help and the drugs themselves have potential side-effects.

‘That is why we are interested in prevention with amitriptyline,’ he adds.

Dr Gulve says the lack of effective treatments for the long-term pain means it’s important that patients seek help quickly if they suspect it might be shingles as antivirals can stop the virus replicating.

The virus damages nerves, and the longer it’s around then the more damage it can do, says Professor Pickering.

‘The pain is the result of this damage to nerve cells. Therefore, if antivirals reduce the replication of the virus and speed its elimination, they should hasten the end of the shingles and reduce the risk of long-term pain.

‘However, this has not been convincingly demonstrated in studies, possibly because of the damage already done by the virus before people go to their GP — so we would encourage patients to go to their GP as early as possible.’

One study, updated in the Journal of Medical Virology in 2021, found that only 54 per cent of patients received antiviral treatment within 72 hours. Antivirals need to be given in the first few days of infection.

‘A key issue is lack of recognition,’ says Matthew Ridd, a professor of primary healthcare at Bristol University and one of the leaders of the Athena study.

‘Patients may not realise they have a problem that needs to be seen quickly, or that the rash is connected to also feeling under the weather, or other symptoms such as a headache,’ he says. That creates a delay in diagnosis and treatment.

Shingles presents as a rash on one side of the body, and pain in the area may precede the rash — which won’t cross the midline,’ he says (in layman’s terms, the nerves run down the body, rather than across). ‘There might also be general malaise.’

As well as long-term pain, shingles can also lead to a raised risk of cardiovascular problems. The theory is the virus causes vascular changes which lead to blockages in the blood vessels.

A study published by Brigham and Women’s Hospital in the U.S. in November found shingles was linked to an almost 30 per cent increased risk of heart attacks or strokes in those without previous cardiovascular problems.

There is no cure for shingles, but a vaccine, Zostavax, is available on the NHS to anyone in their 70s. But uptake rates in England dropped from 61.8 per cent of 70-year-olds in 2013/14 to 26.5 per cent in 2019/20, largely because of a lack of access to GPs during the pandemic.

‘If your GP hasn’t invited you to have it, ask for it,’ advises Marian Nicholson, director of the Herpes Viruses Association and Shingles Support Society.

Today, David is ‘slowly getting back to normal’.

But he adds: ‘I still have a burning sensation around my forehead and a feeling that something is sticking in my left eye. I wouldn’t wish what I’ve been through on anyone.’

The Athena trial is recruiting recently diagnosed patients: athena-study.bristol.ac.uk.

 Dr Megan Rossi is away

Adventurer and TV presenter Bear Grylls, 48, answers our health quiz

Under the microscope 

Adventurer and TV presenter Bear Grylls, 48, answers our health quiz 

Interview by Louise Flind

Can you run up the stairs?

I can and I do! Training is a habit built over many years and takes the form of a body weight routine (25 pull-ups, 50 press-ups, 75 squats and 100 sit-ups) then a weights session every other day. On alternate days, I swim or play touch tennis and I do yoga weekly.

Get your five a day?

I do in terms of fruit but not veg. I’m sceptical about the benefits, to be honest. My diet was vegan/plant-based for years, until I got Covid pretty bad. I doubled down on loads of veg and celery and all that stuff in smoothies but my kidneys got really painful. Then my eldest son [now 19], who’d been struggling with his energy, skin and stomach, got help and was weaned back to great health by eating red meat, butter, eggs, fruit and honey, and cutting out bread, pasta and veg. I couldn’t believe the transformation, but the same happened to me and I’ve now embraced an ancestral/carnivore approach — predominantly grass-fed red meat and liver, rice, eggs and dairy, with fruit and honey to finish.

My diet was vegan/plant-based for years, until I got Covid pretty bad 

Ever dieted?

Yes, but I’d be lean yet lose strength and was always hungry. Now I feel full every day, yet am fitter and leaner than ever [at 6ft, he weighs 12st 4lb].

Any vices?

Pina coladas and Dairy Milk chocolate (a square or two after meals). If I want the odd treat, that’s fine: you’ve got to live a little!

Family ailments?

My father died a few days after having a pacemaker fitted. He was 66. It was the worst moment of my life. The truth is he probably wasn’t active enough and thought eating margarine and no red meat was healthy, when actually he needed natural foods.

Worst illness/injury?

When I was 22, I broke my back when my parachute failed to open. I was lucky not to be paralysed, and spent a long time in military rehabilitation [he was in the 21 (Reserve) SAS]. It made me realise life is so precious, and I vowed to live with total commitment, energy and gratitude.

If I want the odd treat, that’s fine: you’ve got to live a little! 

Pop any pills?

I take Ancestral Supplements [his own range] which include a lot of the organs that are harder to eat in natural form, such as heart, lung, blood and bone marrow. They’re like nature’s best multivitamin.

Ever been depressed?

When Shara and I married [2000], we lost our fathers within a few months. I felt low but simple things helped: sunlight, cold water, good friends, sharing the struggles, being outside, training hard and setting goals.

What keeps you awake?

I worry about my 82-year-old mum because I know movement is so key to longevity but she is less mobile now.

Any phobias?

To this day, I feel the fear before I skydive. But never run from fears or they grow.

ancestralsupplements.com

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Even bivalent updated COVID-19 boosters struggle to prevent omicron subvariant transmission – an immunologist discusses why new approaches are necessary

By almost any measure, the vaccination campaign against SARS-CoV-2, the virus that causes COVID-19, has been a global success.

As of January 2023, more than 12 billion vaccines against SARS-CoV-2 have been administered in an effort that has saved countless lives – more than 14 million in the first year of vaccine availability alone. With a 95% efficacy in the prevention of severe infection and death, and better safety profiles than similar historically effective vaccines, the biomedical community hoped that a combination of vaccination and natural immunity might bring the pandemic to a relatively quick end.

But the emergence of new viral variants, particularly omicron and its array of subvariants, upended those expectations. The latest omicron strain, XBB.1.5. – dubbed “Kraken”, after a mythical sea creature – has rapidly become the dominant subvariant in the U.S. The World Health Organization is calling it the most contagious strain so far, with its success almost certainly attributable to an ability to dodge immunity from previous vaccines or infections.

The effort to get ahead of these ever-changing variants is also in part what has led the Food and Drug Administration to reconsider its approach to COVID-19 vaccination. On Jan. 23, 2023, the agency proposed that current guidelines for a series of shots followed by a booster be replaced by an annual COVID-19 vaccine that is updated each year to combat current strains. The proposal is set to be reviewed by the FDA’s science advisory committee on Jan. 26.

Limitations of current mRNA vaccination strategies

Unfortunately, the new bivalent shots, which include components from both the original SARS-CoV-2 strain as well as a recent omicron variant, have not performed as well as some scientists had hoped. Although there is no question that the updated jabs are capable of boosting antibody levels against SARS-CoV-2 and helping to prevent severe illness and hospitalization, several studies have suggested that they are not necessarily more capable of preventing omicron infections than their predecessors.

As an immunologist who studies how the immune system selects which antibodies to produce and immune responses to COVID-19, these new results are disappointing. But they are not entirely unexpected.

When COVID-19 vaccines were being rolled out in early 2021, immunologists began having public discussions about the potential obstacles to rapidly generating updated vaccines to emerging viral strains. At the time, there was no hard data. But researchers have known for a very long time that immunological memory, the very thing that offers continued protection against a virus long after vaccination, can sometimes negatively interfere with the development of slightly updated immune responses.

The failure of these new bivalent vaccines in widely preventing omicron infections suggests that our current approach is simply not sufficient to interrupt the viral transmission cycle driving the COVID-19 pandemic. In my view, it’s clear that innovative vaccine designs capable of producing a broader immunity are badly needed.

Vaccines are designed to generate immune memory

In simplest terms, vaccines are a way to give your immune system a sneak peek at a pathogen. There are several different ways to do this. One way is to inject inactivated versions of a virus, as has been done with polio. Another is to use noninfectious viral components, such as the proteins used for flu vaccines.

And most recently, scientists have found ways to deliver mRNA “instructions” that tell your body how to make those noninfectious viral components. This is the approach used with the Moderna and Pfizer vaccines targeted against COVID-19.

The mRNA-based vaccines all train your immune system to identify and respond against critical components of a potential invader. An important part of that response is to get your body to produce antibodies that will hopefully prevent future infections, helping to break the cycle of person-to-person transmission.

In a successful response, the immune system will not only produce antibodies that are specific to the pathogen, but will also remember how to make them in case you encounter that same pathogen again in the future.

The existing approach to COVID-19 vaccines has proved effective at preventing serious illness and death, but it has not prevented infections as well as scientists had hoped. Morsa Images/DigitalVision via Getty Images

The specter of ‘original antigenic sin’

But what happens when the virus evolves and that memory becomes obsolete?

Immunologists have wondered this since the initial COVID-19 vaccine rollout. Recently, it has found new relevance in light of the FDA’s proposal for an updated annual COVID-19 shot.

While it is possible that immune responses to updated vaccines will simply replace the old ones, that has not been true for influenza. With flu, researchers have learned that preexisting immunity to one strain can actively inhibit the ability to respond well against another.

Put in everyday language, think of a virus as a car trying to run you over. You might produce one kind of antibody against the hood, one against the bumper and one against the hubcaps that prevents the wheels from turning. You have produced three kinds of antibodies specific to the car, but it turns out that only the hubcap antibodies effectively slow it down.

Now the car mutates, like SARS-CoV-2 has. It changes the shape of the hubcaps or it removes them altogether. Your immune system still recognizes the car, but not the hubcaps. The system doesn’t know that the hubcap was the only effective target, so it ignores the hubcaps and ramps up its attack on the hood and bumper.

In ignoring the new hubcap response, the immune system’s memory of the original car is not only obsolete, but it is also actively interfering with the response necessary to target the new car’s wheels. This is what immunologists call “original antigenic sin” – ineffective immune memory that hampers desired responses to new pathogen strains.

This sort of interference has been extremely difficult to quantify and study in humans, although it may become easier with the FDA’s proposal. A once-yearly approach to COVID-19 vaccination opens the door for more straightforward studies on how memory to each vaccine influences the next.

Multi-strain vaccinations offer hope

Simultaneously, significant efforts are being made to prioritize the pursuit of a single-shot or “universal” vaccine. One approach has been to take advantage of emerging research showing that if your immune system is presented with multiple versions of the same pathogen, it will tend to choose targets that are shared between them.

Presented with a Model T, Ford F-150 and electric Mustang all at once, your immune system will often choose to ignore differences like the hubcaps in favor of similarities like the shape and rubber on the tires. Not only would this interfere with the function of all three vehicles, but it could theoretically interfere with most road-based vehicles – or viral threats such as variants.

Researchers have begun making rapid headway using this approach with the development of complex multi-strain flu vaccines that are performing well in early clinical trials. New studies focused on SARS-CoV-2 hope to do the same. Persistent pathogens including influenza and HIV all suffer from versions of the same antibody-targeting issues. It is possible that this pandemic may serve as a crucible of innovation that leads to the next generation of infectious disease prevention.

This is an updated version of an article originally published on March 8, 2021.

This article is republished from The Conversation, an independent nonprofit news site dedicated to sharing ideas from academic experts. If you found it interesting, you could subscribe to our weekly newsletter.

It was written by: Matthew Woodruff, Emory University.

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Matthew Woodruff does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

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Woman pleads for Utahns to get HPV vaccine to prevent cervical cancer

Estimated read time: 2-3 minutes

SALT LAKE CITY — January is Cervical Cancer Awareness Month and approximately 14,000 women in the U.S. are diagnosed with this type of cancer each year.

Dr. Jonathan Grant, a radiation oncologist, at Intermountain Healthcare said long-lasting infections of human papillomavirus are the main cause of cervical cancer.

“Cervical cancer is unique because it is one of few cancers that is simulated by a virus,” he said.

There is now a vaccine to help prevent this disease, the HPV vaccine.

The American Cancer Society said cervical cancer rates have dropped 65% from 2012 to 2019 after a generation of young women were vaccinated against HPV for the first time.

“The HPV vaccine is one of the great success stories over the last ten to twenty years,” Grant said.

West Valley resident Marianne Peterson, 40, was diagnosed with cervical cancer in September of 2021.

“I just felt like I was floating. It was surreal to be diagnosed with cervical cancer,” she said.

Her last two pap smears came back with abnormal cells and a month before her next yearly checkup she started having heavy bleeding.

Grant said that is a sign of cervical cancer. She started chemotherapy and radiation treatment immediately.

“I had never felt that sick in my whole life,” she said.

But she kept fighting through the sickness.

“It was mostly making sure I was here to take care of my kids and my dogs but mostly my kids,” Peterson said.

Peterson is now cancer free and spends her time camping with family and friends.

She said if the vaccine was available when she was younger, she would have gotten it. “I just think if there is a vaccine that reduces the risk of getting this disease it’s an absolute no brainer,” Peterson said.

Grant says the HPV vaccine is recommended for boys and girls between the ages of nine and 26 and before they are sexually active.

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Moderna’s experimental cancer vaccine treats but doesn’t prevent melanoma – a biochemist explains how it works

Media outlets have reported the encouraging findings of clinical trials for a new experimental vaccine developed by the biotech company Moderna to treat an aggressive type of skin cancer called melanoma.

Although this is potentially very good news, it occurred to me that the headlines may be unintentionally misleading. The vaccines most people are familiar with prevent disease, whereas this experimental new skin cancer vaccine treats only patients who are already sick. Why is it called a vaccine if it does not prevent cancer?

I am a biochemist and molecular biologist studying the roles that microbes play in health and disease. I also teach cancer genetics to medical students and am interested in how the public understands science. While preventive and therapeutic vaccines are administered for different health care goals, they both train the immune system to recognize and fight off a specific disease agent that causes illness.

How do preventive vaccines work?

Most vaccines are administered to healthy people before they get sick to prevent illnesses caused by viruses or bacteria. These include vaccines that prevent polio, measles, COVID-19 and many other diseases. Researchers have also developed vaccines to prevent some types of cancers that are caused by such viruses as the human papillomaviruses and Epstein-Barr virus.

Your immune system recognizes objects such as certain microbes and allergens that do not belong in your body and initiates a series of cellular events to attack and destroy them. Thus, a virus or bacterium that enters the body is recognized as something foreign and triggers an immune response to fight off the microbial invader. This results in a cellular memory that will elicit an even faster immune response the next time the same microbe intrudes.

The problem is that sometimes the initial infection causes serious illness before the immune system can mount a response against it. While you may be better protected against a second infection, you have suffered the potentially damaging consequences of the first one.

This is where preventive vaccines come in. By introducing a harmless version or a portion of the microbe to the immune system, the body can learn to mount an effective response against it without causing the disease.

For example, the Gardasil-9 vaccine protects against the human papillomavirus, or HPV, which causes cervical cancer. It contains protein components found in the virus that cannot cause disease but do elicit an immune response that protects against future HPV infection, thereby preventing cervical cancer.

How does the Moderna cancer vaccine work?

Unlike cervical cancer, skin melanoma isn’t caused by a viral infection, according the latest evidence. Nor does Moderna’s experimental vaccine prevent cancer as Gardasil-9 does.

The Moderna vaccine trains the immune system to fight off an invader in the same way preventive vaccines most people are familiar with do. However, in this case the invader is a tumor, a rogue version of normal cells that harbors abnormal proteins that the immune system can recognize as foreign and attack.

What are these abnormal proteins and where do they come from?

All cells are made up of proteins and other biological molecules such as carbohydrates, lipids and nucleic acids. Cancer is caused by mutations in regions of genetic material, or DNA, that encode instructions on what proteins to make. Mutated genes result in abnormal proteins called neoantigens that the body recognizes as foreign. That can trigger an immune response to fight off a nascent tumor. However, sometimes the immune response fails to subdue the cancer cells, either because the immune system is unable to mount a strong enough response or the cancer cells have found a way to circumvent the immune system’s defenses.

Moderna’s experimental melanoma vaccine contains genetic information that encodes for portions of the neoantigens in the tumor. This genetic information is in the form of mRNA, which is the same form used in the Moderna and Pfizer-BioNtech COVID-19 vaccines. Importantly, the vaccine cannot cause cancer, because it encodes for only small, nonfunctional parts of the protein. When the genetic information is translated into those protein pieces in the body, they trigger the immune system to mount an attack against the tumor. Ideally, this immune response will cause the tumor to shrink and disappear.

Notably, the Moderna melanoma vaccine is tailor-made for each patient. Each tumor is unique, and so the vaccine needs to be unique as well. To customize vaccines, researchers first biopsy the patient’s tumor to determine what neoantigens are present. The vaccine manufacturer then designs specific mRNA molecules that encode those neoantigens. When this custom mRNA vaccine is administered, the body translates the genetic material into proteins specific to the patient’s tumor, resulting in an immune response against the tumor.

Combining vaccination with immunotherapy

Vaccines are a form of immunotherapy, because they treat diseases by harnessing the immune system. However, other immunotherapy cancer drugs are not vaccines because, while they also stimulate the immune system, they do not target specific neoantigens.

In fact, the Moderna vaccine is co-administered with the immunotherapy drug pembrolizumab, which is marketed as Keytruda. Why are two drugs needed?

Certain immune cells called T-cells have molecular accelerator and brake components that serve as checkpoints to ensure they are revved up only in the presence of a foreign invader such as a tumor. However, sometimes tumor cells find a way to keep the T-cell brakes on and suppress the immune response. In these cases, the Moderna vaccine correctly identifies the tumor, but T-cells cannot respond to it.

Pembrolizumab, however, can bind directly to a brake component on the T-cell, inactivating the brake system and allowing the immune cells to attack the tumor.

Not a preventive cancer vaccine

So why can’t the Moderna vaccine be administered to healthy people to prevent melanoma before it arises?

Cancers are highly variable from person to person. Each melanoma harbors a different neoantigen profile that cannot be predicted in advance. Therefore, a vaccine cannot be developed in advance of the illness.

The experimental mRNA melanoma vaccine, currently still in early-phase clinical trials, is an example of the new frontier of personalized medicine. By understanding the molecular basis of diseases, researchers can explore how their underlying causes vary among people, and offer personalized therapeutic options against those diseases.

This article is republished from The Conversation, a nonprofit news site dedicated to sharing ideas from academic experts. If you found it interesting, you could subscribe to our weekly newsletter.

It was written by: Mark R. O’Brian, University at Buffalo.

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Mark R. O’Brian receives funding from the National Institutes of Health.

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Vaccination to prevent dementia? New research suggests one way viral infections can accelerate neurodegeneration

One in nine Americans ages 65 and over had Alzheimer’s disease in 2022, and countless others were indirectly affected as caregivers, health care providers and taxpayers. There is currently no cure – available treatments primarily focus on prevention by encouraging protective factors, such as exercise and healthy diet, and reducing aggravating factors, such as diabetes and high blood pressure.

One of these aggravating factors is viral infections. Researchers have identified that certain viruses such as herpes simplex virus type 1 (HSV-1, which causes cold sores), varicella zoster virus (VZV, which causes chickenpox and shingles) and SARS-CoV-2 (which causes COVID-19) can lead to a higher risk of Alzheimer’s disease and dementia following infection.

Figuring out how and when these viruses contribute to disease could help scientists develop new therapies to prevent dementia. However, researchers have been unable to consistently detect suspect viruses in brains of people who died of Alzheimer’s. Because the Alzheimer’s disease process can start decades before symptoms, some researchers have proposed that viruses act early in a “hit-and-run” manner; they trigger a cascade of events that lead to dementia but have already taken off. In other words, by the time researchers analyze patient brains, any detectable viral components are gone and causation is difficult to establish.

We are a neurovirologist, neurologist and neuroscientist team interested in the role viruses play in neurodegenerative diseases. In our recently published research, we use new technology to search for the tire tracks of these viruses in Alzheimer’s patients. By focusing on the most vulnerable entry point to the brain, the nose, we discovered a genetic network that provides evidence of a robust viral response.

Focusing on the olfactory system

Many of the viruses implicated in dementia, including herpesviruses and the virus that causes COVID-19, enter the nose and interact with the olfactory system.

The olfactory system is constantly bombarded with odors, pollutants and pathogens. Particles inhaled through the nostrils bind to specific olfactory receptor cells in the tissue lining the nasal cavity. These receptors send messages to other cells in what’s called the olfactory bulb, which acts like a relay station that transmits these messages down the long nerves of the olfactory tract. These messages are then transferred to the area of the brain responsible for learning and memory, the hippocampus.

The hippocampus plays a critical role assigning contextual information to odors, such as danger from the foul smell of propane or comfort from the smell of lavender. This area of the brain is also dramatically damaged in Alzheimer’s disease, causing devastating learning and memory deficits. For as many as 85% to 90% of Alzheimer’s patients, loss of smell is an early sign of disease.

The mechanism leading to smell loss in Alzheimer’s disease is relatively unknown. Like muscles that atrophy from lack of use, sensory deprivation is thought to lead to atrophy of the brain regions that specialize in interpreting sensory information. Strong sensory input to these regions is critical to maintain general brain health.

Olfactory inflammation and Alzheimer’s disease

We hypothesize that viral infections throughout life are both contributors to and potential drug targets in Alzheimers’s disease. To test this idea, we used emerging, state-of-the-art technology to investigate the mRNA and protein networks of the olfactory system of Alzheimer’s disease patients.

The body uses mRNA, which is transcribed from DNA, to translate genetic material into proteins. The body uses specific mRNA sequences to produce a network of proteins that are used to fight against certain viruses. In some cases, the body continues to activate these pathways even after the the virus is cleared, leading to chronic inflammation and tissue damage. Identifying which mRNA sequences and protein networks are present can allow us to infer, to a degree, whether the body is or was responding to a viral pathogen at some point.

Previously, sequencing mRNA in tissue samples was difficult because the molecules degrade very quickly. However, new technology specifically addresses that issue by measuring small subsections of mRNA at a time instead of trying to reconstruct the whole mRNA sequence at once.

We leveraged this technology to sequence the mRNA of olfactory bulb and olfactory tract samples from six people with familial Alzheimer’s, an inherited form of the disease, and six people without Alzheimer’s. We focused on familial Alzheimer’s because there is less variability in disease than in the sporadic, or nonfamilial, form of the disease, which can result from a number of different individual and environmental factors.

This image shows neurons in a small cross section of a mouse’s olfactory bulb. (Credit: Jeremy McIntyre/University of Florida College of Medicine via National Institutes of Health, CC BY-NC)

In the familial Alzheimer’s samples, we found altered gene expression indicating signs of a past viral infection in the olfactory bulb, as well as inflammatory immune responses in the olfactory tract. We also found higher levels of proteins involved in demyelination in the olfactory tract of familial Alzheimer’s samples than in the controls. Myelin is a protective fatty layer around nerves that allows electrical impulses to move quickly and smoothly from one area of the brain to another. Damage to myelin stalls signal transduction, resulting in impaired neural communication and, by extension, neurodegeneration.

Based on these findings, we hypothesize that viral infections, and the resulting inflammation and demyelination within the olfactory system, may disrupt the function of the hippocampus by impairing communication from the olfactory bulb. This scenario could contribute to the accelerated neurodegeneration seen in Alzheimer’s disease.

Implications for patient health

Epidemiological data supports the role of viral infections in the development of Alzheimer’s disease. For example, the varicella zoster virus is linked to a nearly threefold risk of developing dementia within five years of infection for patients with a shingles rash on their face. A recent report also found a nearly 70% increased risk of getting diagnosed with Alzheimer’s within a year of a COVID-19 diagnosis for people over 65.

These studies suggest that vaccination may be a potential measure to prevent dementia. For example, vaccination against the seasonal flu virus and herpes zoster is associated with an up to 29% and 30% reduced risk of developing dementia, respectively.

Further research investigating how viral infections can trigger neurodegeneration could aid in the development of antiviral drugs and vaccines against the viruses implicated in Alzheimer’s disease.

Report written by Andrew Bubak, Assistant Research Professor of Neurology; Diego Restrepo, Professor of Cell and Developmental Biology; and Maria Nagel, Professor of Neurology and Ophthalmology, all from the University of Colorado Anschutz Medical Campus. This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Cancer Vaccine to Simultaneously Kill and Prevent Brain Cancer Developed

Summary: A new stem cell therapy approach eliminates established brain tumors and provides long-term immunity, training the immune system to prevent cancer from returning.

Source: Brigham and Women’s Hospital

Scientists are harnessing a new way to turn cancer cells into potent, anti-cancer agents.

In the latest work from the lab of Khalid Shah, MS, Ph.D., at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, investigators have developed a new cell therapy approach to eliminate established tumors and induce long-term immunity, training the immune system so that it can prevent cancer from recurring.

The team tested their dual-action, cancer-killing vaccine in an advanced mouse model of the deadly brain cancer glioblastoma, with promising results.

Findings are published in Science Translational Medicine.

“Our team has pursued a simple idea: to take cancer cells and transform them into cancer killers and vaccines,” said corresponding author Khalid Shah, MS, Ph.D., director of the Center for Stem Cell and Translational Immunotherapy (CSTI) and the vice chair of research in the Department of Neurosurgery at the Brigham and faculty at Harvard Medical School and Harvard Stem Cell Institute (HSCI).

“Using gene engineering, we are repurposing cancer cells to develop a therapeutic that kills tumor cells and stimulates the immune system to both destroy primary tumors and prevent cancer.”

Cancer vaccines are an active area of research for many labs, but the approach that Shah and his colleagues have taken is distinct. Instead of using inactivated tumor cells, the team repurposes living tumor cells, which possess an unusual feature. Like homing pigeons returning to roost, living tumor cells will travel long distances across the brain to return to the site of their fellow tumor cells.

Taking advantage of this unique property, Shah’s team engineered living tumor cells using the gene editing tool CRISPR-Cas9 and repurposed them to release tumor cell killing agent.

In addition, the engineered tumor cells were designed to express factors that would make them easy for the immune system to spot, tag and remember, priming the immune system for a long-term anti-tumor response.

Scientists developed a bifunctional therapeutic strategy by transforming living tumor cells into a therapeutic. Shah’s team engineered living tumor cells using the gene editing tool CRISPR-Cas9 and repurposed them to release tumor cell killing agent. In addition, the engineered tumor cells were designed to express factors that would make them easy for the immune system to spot, tag and remember, priming the immune system for a long-term anti-tumor response. The team tested their repurposed CRISPR-enhanced and reverse-engineered therapeutic tumor cells (ThTC) in different mice strains including the one that bore bone marrow, liver and thymus cells derived from humans, mimicking the human immune microenvironment. Shah’s team also built a two-layered safety switch into the cancer cell, which, when activated, eradicates ThTCs if needed. Credit: Kok Siong Chen and Khalid Shah.

The team tested their repurposed CRISPR-enhanced and reverse-engineered therapeutic tumor cells (ThTC) in different mice strains including the one that bore bone marrow, liver and thymus cells derived from humans, mimicking the human immune microenvironment. Shah’s team also built a two-layered safety switch into the cancer cell, which, when activated, eradicates ThTCs if needed.

This dual-action cell therapy was safe, applicable, and efficacious in these models, suggesting a roadmap toward therapy. While further testing and development is needed, Shah’s team specifically chose this model and used human cells to smooth the path of translating their findings for patient settings.

“Throughout all of the work that we do in the Center, even when it is highly technical, we never lose sight of the patient,” said Shah.

“Our goal is to take an innovative but translatable approach so that we can develop a therapeutic, cancer-killing vaccine that ultimately will have a lasting impact in medicine.”

Shah and colleagues note that this therapeutic strategy is applicable to a wider range of solid tumors and that further investigations of its applications are warranted.

About this brain cancer research news

Author: Press Office
Source: Brigham and Women’s Hospital
Contact: Press Office – Brigham and Women’s Hospital
Image: The image is credited to Kok Siong Chen and Khalid Shah

See also

Original Research: Open access.
“Bifunctional cancer cell-based vaccine concomitantly drives direct tumor killing and antitumor immunity” by Kok-Siong Chen et al. Science Translational Medicine


Abstract

Bifunctional cancer cell-based vaccine concomitantly drives direct tumor killing and antitumor immunity

The administration of inactivated tumor cells is known to induce a potent antitumor immune response; however, the efficacy of such an approach is limited by its inability to kill tumor cells before inducing the immune responses. Unlike inactivated tumor cells, living tumor cells have the ability to track and target tumors.

Here, we developed a bifunctional whole cancer cell–based therapeutic with direct tumor killing and immunostimulatory roles. We repurposed the tumor cells from interferon-β (IFN-β) sensitive to resistant using CRISPR-Cas9 by knocking out the IFN-β–specific receptor and subsequently engineered them to release immunomodulatory agents IFN-β and granulocyte-macrophage colony-stimulating factor.

These engineered therapeutic tumor cells (ThTCs) eliminated established glioblastoma tumors in mice by inducing caspase-mediated cancer cell apoptosis, down-regulating cancer-associated fibroblast-expressed platelet-derived growth factor receptor β, and activating antitumor immune cell trafficking and antigen-specific T cell activation signaling.

This mechanism-based efficacy of ThTCs translated into a survival benefit and long-term immunity in primary, recurrent, and metastatic cancer models in immunocompetent and humanized mice. The incorporation of a double kill-switch comprising herpes simplex virus–1 thymidine kinase and rapamycin-activated caspase 9 in ThTCs ensured the safety of our approach.

Arming naturally neoantigen-rich tumor cells with bifunctional therapeutics represents a promising cell-based immunotherapy for solid tumors and establishes a road map toward clinical translation.

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