The Path to a Better Tuberculosis Vaccine Runs Through Montana
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A team of Montana researchers is playing a key role in the development of a more effective vaccine against tuberculosis, an infectious disease that has killed more people than any other.
The BCG (Bacille Calmette-Guérin) vaccine, created in 1921, remains the sole TB vaccine. While it is 40% to 80% effective in young children, its efficacy is very low in adolescents and adults, leading to a worldwide push to create a more powerful vaccine.
One effort is underway at the University of Montana Center for Translational Medicine. The center specializes in improving and creating vaccines by adding what are called novel adjuvants. An adjuvant is a substance included in the vaccine, such as fat molecules or aluminum salts, that enhances the immune response, and novel adjuvants are those that have not yet been used in humans. Scientists are finding that adjuvants make for stronger, more precise, and more durable immunity than antigens, which create antibodies, would alone.
Eliciting specific responses from the immune system and deepening and broadening the response with adjuvants is known as precision vaccination. “It’s not one-size-fits-all,” said Ofer Levy, a professor of pediatrics at Harvard University and the head of the Precision Vaccines Program at Boston Children’s Hospital. “A vaccine might work differently in a newborn versus an older adult and a middle-aged person.”
The ultimate precision vaccine, said Levy, would be lifelong protection from a disease with one jab. “A single-shot protection against influenza or a single-shot protection against covid, that would be the holy grail,” Levy said.
Jay Evans, the director of the University of Montana center and the chief scientific and strategy officer and a co-founder of Inimmune, a privately held biotechnology company in Missoula, said his team has been working on a TB vaccine for 15 years. The private-public partnership is developing vaccines and trying to improve existing vaccines, and he said it’s still five years off before the TB vaccine might be distributed widely.
It has not gone unnoticed at the center that this state-of-the-art vaccine research and production is located in a state that passed one of the nation’s most extreme anti-vaccination laws during the pandemic in 2021. The law prohibits businesses and governments from discriminating against people who aren’t vaccinated against covid-19 or other diseases, effectively banning both public and private employers from requiring workers to get vaccinated against covid or any other disease. A federal judge later ruled that the law cannot be enforced in health care settings, such as hospitals and doctors’ offices.
In mid-March, the Bill & Melinda Gates Medical Research Institute announced it had begun the third and final phase of clinical trials for the new vaccine in seven countries. The trials should take about five years to complete. Research and production are being done in several places, including at a manufacturing facility in Hamilton owned by GSK, a giant pharmaceutical company.
Known as the forgotten pandemic, TB kills up to 1.6 million people a year, mostly in impoverished areas in Asia and Africa, despite its being both preventable and treatable. The U.S. has seen an increase in tuberculosis over the past decade, especially with the influx of migrants, and the number of cases rose by 16% from 2022 to 2023. Tuberculosis is the leading cause of death among people living with HIV, whose risk of contracting a TB infection is 20 times as great as people without HIV.
“TB is a complex pathogen that has been with human beings for ages,” said Alemnew Dagnew, who heads the program for the new vaccine for the Gates Medical Research Institute. “Because it has been with human beings for many years, it has evolved and has a mechanism to escape the immune system. And the immunology of TB is not fully understood.”
The University of Montana Center for Translational Medicine and Inimmune together have 80 employees who specialize in researching a range of adjuvants to understand the specifics of immune responses to different substances. “You have to tailor it like tools in a toolbox towards the pathogen you are vaccinating against,” Evans said. “We have a whole library of adjuvant molecules and formulations.”
Vaccines are made more precise largely by using adjuvants. There are three basic types of natural adjuvants: aluminum salts; squalene, which is made from shark liver; and some kinds of saponins, which are fat molecules. It’s not fully understood how they stimulate the immune system. The center in Missoula has also created and patented a synthetic adjuvant, UM-1098, that drives a specific type of immune response and will be added to new vaccines.
One of the most promising molecules being used to juice up the immune system response to vaccines is a saponin molecule from the bark of the quillay tree, gathered in Chile from trees at least 10 years old. Such molecules were used by Novavax in its covid vaccine and by GSK in its widely used shingles vaccine, Shingrix. These molecules are also a key component in the new tuberculosis vaccine, known as the M72 vaccine.
But there is room for improvement.
“The vaccine shows 50% efficacy, which doesn’t sound like much, but basically there is no effective vaccine currently, so 50% is better than what’s out there,” Evans said. “We’re looking to take what we learned from that vaccine development with additional adjuvants to try and make it even better and move 50% to 80% or more.”
By contrast, measles vaccines are 95% effective.
According to Medscape, around 15 vaccine candidates are being developed to replace the BCG vaccine, and three of them are in phase 3 clinical trials.
One approach Evans’ center is researching to improve the new vaccine’s efficacy is taking a piece of the bacterium that causes TB, synthesizing it, and combining it with the adjuvant QS-21, made from the quillay tree. “It stimulates the immune system in a way that is specific to TB and it drives an immune response that is even closer to what we get from natural infections,” Evans said.
The University of Montana center is researching the treatment of several problems not commonly thought of as treatable with vaccines. They are entering the first phase of clinical trials for a vaccine for allergies, for instance, and first-phase trials for a cancer vaccine. And later this year, clinical trials will begin for vaccines to block the effects of opioids like heroin and fentanyl. The University of Montana received the largest grant in its history, $33 million, for anti-opioid vaccine research. It works by creating an antibody that binds with the drug in the bloodstream, which keeps it from entering the brain and creating the high.
For now, though, the eyes of health care experts around the world are on the trials for the new TB vaccines, which, if they are successful, could help save countless lives in the world’s poorest places.
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.
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Why does alcohol make my poo go weird?
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As we enter the festive season it’s a good time to think about what all those celebratory alcoholic drinks can do to your gut.
Alcohol can interfere with the time it takes for food to go through your gut (also known as the “transit time”). In particular, it can affect the muscles of the stomach and the small bowel (also known as the small intestine).
So, how and why does alcohol make your poos goes weird? Here’s what you need to know.
Diarrhoea and the ‘transit time’
Alcohol’s effect on stomach transit time depends on the alcohol concentration.
In general, alcoholic beverages such as whisky and vodka with high alcohol concentrations (above 15%) slow down the movement of food in the stomach.
Beverages with comparatively low alcohol concentrations (such as wine and beer) speed up the movement of food in the stomach.
These changes in gut transit explain why some people can get a sensation of fullness and abdominal discomfort when they drink vodka or whisky.
How long someone has been drinking a lot of alcohol can affect small bowel transit.
We know from experiments with rats that chronic use of alcohol accelerates the transit of food through the stomach and small bowel.
This shortened transit time through the small bowel also happens when humans drink a lot of alcohol, and is linked to diarrhoea.
Alcohol can also reduce the absorption of carbohydrates, proteins and fats in the duodenum (the first part of the small bowel).
Alcohol can lead to reduced absorption of xylose (a type of sugar). This means diarrhoea is more likely to occur in drinkers who also consume a lot of sugary foods such as sweets and sweetened juices.
Chronic alcohol use is also linked to:
- lactose intolerance
- overgrowth of small bowel bacteria and
- reduced absorption of fats from the pancreas not producing enough digestive enzymes.
This means chronic alcohol use may lead to diarrhoea and loose stools.
How might a night of heavy drinking affect your poos?
When rats are exposed to high doses of alcohol over a short period of time, it results in small bowel transit delay.
This suggests acute alcohol intake (such as an episode of binge drinking) is more likely to lead to constipation than diarrhoea.
This is backed up by recent research studying the effects of alcohol in 507 university students.
These students had their stools collected and analysed, and were asked to fill out a stool form questionnaire known as the Bristol Stool Chart.
The research found a heavy drinking episode was associated with harder, firm bowel motions.
In particular, those who consumed more alcohol had more Type 1 stools, which are separate hard lumps that look or feel a bit like nuts.
The researchers believed this acute alcohol intake results in small bowel transit delay; the food stayed for longer in the intestines, meaning more water was absorbed from the stool back into the body. This led to drier, harder stools.
Interestingly, the researchers also found there was more of a type of bacteria known as “Actinobacteria” in heavy drinkers than in non-drinkers.
This suggests bacteria may have a role to play in stool consistency.
But binge drinking doesn’t always lead to constipation. Binge drinking in patients with irritable bowel syndrom (IBS), for example, clearly leads to diarrhoea, nausea and abdominal pain.
What can I do about all this?
If you’re suffering from unwanted bowel motion changes after drinking, the most effective way to address this is to limit your alcohol intake.
Some alcoholic beverages may affect your bowel motions more than others. If you notice a pattern of troubling poos after drinking certain drinks, it may be sensible to cut back on those beverages.
If you tend to get diarrhoea after drinking, avoid mixing alcohol with caffeinated drinks. Caffeine is known to stimulate contractions of the colon and so could worsen diarrhoea.
If constipation after drinking is the problem, then staying hydrated is important. Drinking plenty of water before drinking alcohol (and having water in between drinks and after the party is over) can help reduce dehydration and constipation.
You should also eat before drinking alcohol, particularly protein and fibre-rich foods.
Food in the stomach can slow the absorption of alcohol and may help protect against the negative effects of alcohol on the gut lining.
Is it anything to worry about?
Changes in bowel motions after drinking are usually short term and, for the most part, resolve themselves pretty efficiently.
But if symptoms such as diarrhoea persist beyond a couple of days after stopping alcohol, it may signify other concerning issues such as an underlying gut disorder like inflammatory bowel disease.
Researchers have also linked alcohol consumption to the development of irritable bowel syndrome.
If problems persist or if there are alarming symptoms such as blood in your stool, seek medical advice from a general practitioner.
Vincent Ho, Associate Professor and clinical academic gastroenterologist, Western Sydney University
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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How does the drug abemaciclib treat breast cancer?
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The anti-cancer drug abemaciclib (also known as Vernezio) has this month been added to the Australian Pharmaceutical Benefits Scheme (PBS) to treat certain types of breast cancer.
This significantly reduces the cost of the drug. A patient can now expect to pay A$31.60 for a 28-day supply ($7.70 with a health care concession card). The price of abemaciclib without government subsidy is $4,250.
So what is abemaciclib, and how did we get to this point?
It stops cells dividing
Researchers at the pharmaceutical company Eli Lilly developed abemaciclib and published the first study on the drug (then known as LY2835219) in 2014.
Abemaciclib is a type of drug known as a “cyclin-dependent kinase inhibitor”. It’s taken as a pill twice a day.
To maintain our health, many of the cells in our bodies need to grow and divide to produce new cells. Cancers develop when cells grow and divide out of control. Therefore, stopping cells from dividing into new cells is one way that cancer can be fought.
When cells divide, they have to make a copy of their DNA to pass onto the new cell. “Cyclin-dependent kinases” (CDKs for short) are essential for this process. So, if you stop the CDKs, you stop the DNA copying, you stop cells dividing, and you fight the cancer.
However, there are different types of CDKs, and not all cancers need them all to grow. Abemaciclib specifically targets CDK4 and CDK6. Thankfully, a lot of cancers do need these CDKs, including some breast cancers.
The drug targets CDK4 and CDK6. Photoroyalty/Shutterstock But abemaciclib will only be effective against cancers that rely on CDK4 and CDK6 for continued growth. This specificity also means abemaciclib is fairly unique, so it can’t easily be replaced with a different drug.
Two other CDK4/6 inhibitors were developed around the same time as abemaciclib, and are called ribociclib and palbociclib. Both of these drugs are also on the PBS for specific types of breast cancer. As the drugs differ in their chemical structures, they have slight differences in the way they are taken up and processed by the body. The preferred drug given to a breast cancer patient will depend on their unique circumstances.
What are the side effects?
Research is still ongoing into the differences between each of these CDK4/6 inhibitors, but it is known that the side effects are largely similar, but can differ in severity.
The most common side effects of abemaciclib are fatigue, diarrhoea and neutropenia (reduced white blood cells). The gastrointestinal issues are generally more severe with abemaciclib.
If these side effects are too severe, abemaciclib treatment can be stopped.
What types of cancer has abemaciclib been approved for?
In 2017, the United States Food and Drug Administration (FDA) approved abemaciclib for the treatment of patients with metastatic HR+/HER2- (hormone receptor-positive and human epidermal growth factor receptor 2-negative) breast cancer who did not respond to standard endocrine therapy.
Australia’s Therapeutic Goods Administration (TGA) similarly approved abemaciclib in 2022 as an “adjuvant” therapy (after the initial surgery to remove the tumour) for patients with HR+/HER2- invasive early breast cancer which had spread to lymph nodes and was at high risk of returning.
The drug is approved for people with early breast cancer which is at high risk of returning. PeopleImages.com – Yuri A/Shutterstock As of May 1 2024, the PBS covers this use of abemaciclib in combination with endocrine therapy such as fulvestrant, which is also listed on the PBS. Endocrine therapy, also known as hormonal therapy, blocks hormone receptor positive (HR+) cancers from receiving the hormones they need to survive.
Could abemaciclib be used for other cancers in the future?
Abemaciclib is of great interest to scientists and medical practitioners, and testing is ongoing to assess the effectiveness of abemaciclib in treating a range of other cancers, including gastrointestinal cancers and blood cancers.
Abemaciclib may even be usable in brain cancers, as it has long been known to be capable of crossing the blood-brain barrier, a common stumbling block for potential anti-cancer drugs.
Time will tell whether the role of abemaciclib in health care will be expanded. But for now, its inclusion on the PBS is sure to bring some relief to breast cancer patients nationwide.
Sarah Diepstraten, Senior Research Officer, Blood Cells and Blood Cancer Division, Walter and Eliza Hall Institute and John (Eddie) La Marca, Senior Resarch Officer, Walter and Eliza Hall Institute
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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Teen Daily Delivery Requested
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It’s Q&A Day at 10almonds!
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In cases where we’ve already covered something, we might link to what we wrote before, but will always be happy to revisit any of our topics again in the future too—there’s always more to say!
As ever: if the question/request can be answered briefly, we’ll do it here in our Q&A Thursday edition. If not, we’ll make a main feature of it shortly afterwards!
So, no question/request too big or small
I thoroughly enjoy your daily delivery. I’d love to see one for teens too!
That’s great to hear! The average age of our subscribers is generally rather older, but it’s good to know there’s an interest in topics for younger people. We’ll bear that in mind, and see what we can do to cater to that without alienating our older readers!
That said: it’s never too soon to be learning about stuff that affects us when we’re older—there are lifestyle factors at 20 that affect Alzheimer’s risk at 60, for example (e.g. drinking—excessive drinking at 20* is correlated to higher Alzheimer’s risk at 60).
*This one may be less of an issue for our US readers, since the US doesn’t have nearly as much of a culture of drinking under 21 as some places. Compare for example with general European practices of drinking moderately from the mid-teens, or the (happily, diminishing—but historically notable) British practice of drinking heavily from the mid-teens.
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Stop Cancer 20 Years Ago
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Get Abreast And Keep Abreast
This is Dr. Jenn Simmons. Her specialization is integrative oncology, as she—then a breast cancer surgeon—got breast cancer, decided the system wasn’t nearly as good from the patients’ side of things as from the doctors’ side, and took to educate herself, and now others, on how things can be better.
What does she want us to know?
Start now
If you have breast cancer, the best time to start adjusting your lifestyle might be 20 years ago, but the second-best time is now. We realize our readers with breast cancer (or a history thereof) probably have indeed started already—all strength to you.
What this means for those of us without breast cancer (or a history therof) is: start now
Even if you don’t have a genetic risk factor, even if there’s no history of it in your family, there’s just no reason not to start now.
Start what, you ask? Taking away its roots. And how?
Inflammation as the root of cancer
To oversimplify: cancer occurs because an accidentally immortal cell replicates and replicates and replicates and takes any nearby resources to keep on going. While science doesn’t know all the details of how this happens, it is a factor of genetic mutation (itself a normal process, without which evolution would be impossible), something which in turn is accelerated by damage to the DNA. The damage to the DNA? That occurs (often as not) as a result of cellular oxidation. Cellular oxidation is far from the only genotoxic thing out there, and a lot of non-food “this thing causes cancer” warnings are usually about other kinds of genotoxicity. But cellular oxidation is a big one, and it’s one that we can fight vigorously with our lifestyle.
Because cellular oxidation and inflammation go hand-in-hand, reducing one tends to reduce the other. That’s why so often you’ll see in our Research Review Monday features, a line that goes something like:
“and now for those things that usually come together: antioxidant, anti-inflammatory, anticancer, and anti-aging”
So, fight inflammation now, and have a reduced risk of a lot of other woes later.
See: How to Prevent (or Reduce) Inflammation
Don’t settle for “normal”
People are told, correctly but not always helpfully, such things as:
- It’s normal to have less energy at your age
- It’s normal to have a weaker immune system at your age
- It’s normal to be at a higher risk of diabetes, heart disease, etc
…and many more. And these things are true! But that doesn’t mean we have to settle for them.
We can be all the way over on the healthy end of the distribution curve. We can do that!
(so can everyone else, given sufficient opportunity and resources, because health is not a zero-sum game)
If we’re going to get a cancer diagnosis, then our 60s are the decade where we’re most likely to get it. Earlier than that and the risk is extant but lower; later than that and technically the risk increases, but we probably got it already in our 60s.
So, if we be younger than 60, then now’s a good time to prepare to hit the ground running when we get there. And if we missed that chance, then again, the second-best time is now:
See: Focusing On Health In Our Sixties
Fast to live
Of course, anything can happen to anyone at any age (alas), but this is about the benefits of living a fasting lifestyle—that is to say, not just fasting for a 4-week health kick or something, but making it one’s “new normal” and just continuing it for life.
This doesn’t mean “never eat”, of course, but it does mean “practice intermittent fasting, if you can”—something that Dr. Simmons strongly advocates.
See: Intermittent Fasting: We Sort The Science From The Hype
While this calls back to the previous “fight inflammation”, it deserves its own mention here as a very specific way of fighting it.
It’s never too late
All of the advices that go before a cancer diagnosis, continue to stand afterwards too. There is no point of “well, I already have cancer, so what’s the harm in…?”
The harm in it after a diagnosis will be the same as the harm before. When it comes to lifestyle, preventing a cancer and preventing it from spreading are very much the same thing, which is also the same as shrinking it. Basically, if it’s anticancer, it’s anticancer, no matter whether it’s before, during, or after.
Dr. Simmons has seen too many patients get a diagnosis, and place their lives squarely in the hands of doctors, when doctors can only do so much.
Instead, Dr. Simmons recommends taking charge of your health as best you are able, today and onwards, no matter what. And that means two things:
- Knowing stuff
- Doing stuff
So it becomes our responsibility (and our lifeline) to educate ourselves, and take action accordingly.
Want to know more?
We recently reviewed her book, and heartily recommend it:
The Smart Woman’s Guide to Breast Cancer – by Dr. Jenn Simmons
Enjoy!
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Greek Yogurt vs Cottage Cheese – Which is Healthier?
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Our Verdict
When comparing Greek yogurt to cottage cheese, we picked the yogurt.
Why?
These are both dairy products popularly considered healthy, mostly for their high-protein, low-carb, low-fat profile. We’re going to assume that both were made without added sugars. Thus, their macro profiles are close to identical, and nothing between them there.
In the category of vitamins, both are a good source of some B vitamins, and neither are good source of much else. The B-vitamins they have most of, B2 and B12, Greek yogurt has more.
We’ll call this a small win for Greek yogurt.
As they are dairy products, you might have expected them to contain vitamin D—however (unless they have been artificially fortified, as is usually done with plant-based equivalents) they contain none or trace amounts only.
When it comes to minerals, both are reasonable sources of calcium, selenium, and phosphorus. Of these, they’re equal on the selenium, while cottage cheese has more phosphorus and Greek yogurt has more calcium.
Since it’s also a mineral (even if it’s usually one we’re more likely to be trying to get less of), it’s also worth noting here that cottage cheese is quite high in sodium, while Greek yogurt is not.
Another win for Greek yogurt.
Beyond those things, we’d be remiss not to mention that Greek yogurt contains plenty of probiotic bacteria, while cottage cheese does not.
Want to learn more?
You might like to read:
Take care!
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Acorns vs Chestnuts – Which is Healthier?
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Our Verdict
When comparing acorns to chestnuts, we picked the acorns.
Why?
In terms of macros, chestnuts are mostly water, so it’s not surprising that acorns have a lot more carbs, fat, protein, and fiber. Thus, unless you have personal reasons for any of those to be a problem, acorns are the better choice, offering a lot more nutritional value.
In the category of vitamins, acorns lead with a lot more of vitamins A, B2, B3, B5, B6, and B9, while chestnuts have more of vitamins B1 and C. However, that vitamin C is useless to us, because it is destroyed in the cooking process (by boiling or roasting), and both of these nuts can be harmful if consumed raw, so that cooking does need to be done. That leaves acorns with a 6:1 lead.
When it comes to minerals, things are more even; acorns have more copper, magnesium, manganese, and zinc, while chestnuts have more calcium, iron, phosphorus, and potassium. Thus, a 4:4 tie (and yes, the margins of difference are approximately equal too).
We mentioned “both of these nuts can be harmful if consumed raw”, so a note on that: it’s because, while both contain an assortment of beneficial phytochemicals, they also both contain tannins that, if consumed raw, chelate with iron, essentially taking it out of our diet and potentially creating an iron deficiency. Cooking tannins stops this from being an issue, and the same cooking process renders the tannins actively beneficial to the health, for their antioxidant powers.
You may have heard that acorns are poisonous; that’s not strictly speaking true, except insofar as anything could be deemed poisonous in excess (including such things as water, and oxygen). Rather, it’s simply the above-described matter of the uncooked tannins and iron chelation. Even then, you’re unlikely to suffer ill effects unless you consume them raw in a fair quantity. While acorns have fallen from popular favor sufficient that one doesn’t see them in supermarkets, the fact is they’ve been enjoyed as an important traditional part of the diet by various indigenous peoples of N. America for centuries*, and provided they are cooked first, they are a good healthy food for most people.
*(going so far as to cultivate natural oak savannah areas, by burning out young oaks to leave the old ones to flourish without competition, to maximize acorn production, and then store dried acorns in bulk sufficient to cover the next year or so in case of a bad harvest later—so these was not just an incidental food, but very important “our life may depend on this” food. Much like grain in many places—and yes, acorns can be ground into flour and used to make bread etc too)
Do note: they are both still tree nuts though, so if you have a tree nut allergy, these ones aren’t for you.
Otherwise, enjoy both; just cook them first!
Want to learn more?
You might like to read:
Why You Should Diversify Your Nuts
Take care!
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