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SuSanA Secretariat via Wikimedia Commons // CC BY 2.0
SuSanA Secretariat via Wikimedia Commons // CC BY 2.0

Parasitic Worms May Keep Inflammatory Bowel Disease at Bay

SuSanA Secretariat via Wikimedia Commons // CC BY 2.0
SuSanA Secretariat via Wikimedia Commons // CC BY 2.0

Scientists say people infected with parasitic worms may be better able to fend off autoimmune conditions like inflammatory bowel disease (IBD). Their study shows that the infection changes the balance of bacteria in a person’s gut, overpowering the species that cause inflammation. The findings were published last week in the journal Science.

In many ways, human beings are healthier than we’ve ever been before. In other ways … not so much. The lifespan of the average American is longer than ever, but that long life is also more likely to be marked with chronic illness. Among medical conditions on the rise are autoimmune diseases like allergies, type one diabetes, and IBD. Scientists have theorized that the increase in autoimmune diseases may be influenced by our relatively sterile way of life. This hygiene hypothesis, as it’s known, posits that some exposure to germs is good for our immune systems. Without this exposure, our immune systems essentially short-circuit, leaving us vulnerable.

If hand sanitizer and antibiotics are the problem, some people say that worms may be the answer. Experiments have found helminth therapy (as it's called) may help celiac disease, multiple sclerosis, and Crohn’s disease, a form of IBD. Still, researchers have been cautious. “Nobody got hurt, nobody’s eyes fell out,” gastroenterologist Joel Weinstock told Science News in 2014. “But it’s still too early to say, ‘Well golly gee, this is going to be better than apple pie.’”

Apple pie or no, some Americans with chronic conditions can’t stand to wait, and are already intentionally infecting themselves with worms. One man found the treatment so effective that he felt he had to alert parasitologist P’ng Loke.

“I was contacted by an individual who had deliberately infected himself with worms to treat his symptoms of IBD and was able to put his disease into remission,” Loke said in a recorded interview. Loke and his colleagues wondered what, exactly, the worms were doing and how it could be helpful. They suspected that the infection might cause a person’s gut bacteria to re-balance, thereby overpowering the Bacteroides, a genus of “bad” bacteria that can lead to bowel inflammation.

The researchers bred mice that would carry a gene associated with immune conditions, including IBD. They then infected the mice with juvenile whipworms. After the worms had matured, the scientists took bacteria samples from the rodents’ poop and intestines. Sure enough, they found decreased levels of Bacteriodes and increased levels of Clostridia—a species that can reduce inflammation. Helminth infection had swung the bacterial balance in a more constructive direction.

To be sure that these effects were not just a mouse thing, the researchers also tested the gut bacteria of two groups of people in Malaysia: people from a rural area known for having low rates of IBD and high rates of worm infection, and people from a nearby city, for whom the IBD/worm situation was reversed. Once again, the results revealed that the immune response triggered by worm infection seemed to defend the bacterial ecosystem against Bacteroides inflammation.

“Patient testimonials and anecdotes lead many to think that worms directly cure IBD, senior investigator Ken Caldwell said in a press statement, “while in reality, they act on the gut bacteria thought to cause the disease.”

Caldwell and his colleagues believe their findings offer a concrete explanation that may help lead to relief for patients. “Our study could change how scientists and physicians think about treating IBD.”

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Medicine
New Peanut Allergy Patch Could Be Coming to Pharmacies This Year
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iStock

About 6 million people in the U.S. and Europe have severe peanut allergies, including more than 2 million children. Now, French biotechnology company DBV Technologies SA has secured an FDA review for its peanut allergy patch, Bloomberg reports.

If approved, the company aims to start selling the Viaskin patch to children afflicted with peanut allergies in the second half of 2018. The FDA's decision comes in spite of the patch's disappointing study results last year, which found the product to be less effective than DBV hoped (though it did receive high marks for safety). The FDA has also granted Viaskin breakthrough-therapy and fast-track designations, which means a faster review process.

DBV's potentially life-saving product is a small disc that is placed on the arm or between the shoulder blades. It works like a vaccine, exposing the wearer's immune system to micro-doses of peanut protein to increase tolerance. It's intended to reduce the chances of having a severe allergic reaction to accidental exposure.

The patch might have competition: Aimmune Therapeutics Inc., which specializes in food allergy treatments, and the drug company Regeneron Pharmaceuticals Inc. are working together to develop a cure for peanut allergies.

[h/t Bloomberg]

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Essential Science
How Are Vaccines Made?
Quality checks on the Salk polio vaccine at Glaxo's virus research laboratory in Buckinghamshire, UK, in January 1956.
Quality checks on the Salk polio vaccine at Glaxo's virus research laboratory in Buckinghamshire, UK, in January 1956.
Photo by Fox Photos/Getty Images

Vaccines have long been hailed as one of our greatest public health achievements. They can be made to protect us from infections with either viral or bacterial microbes. Measles and smallpox, for example, are viruses; Streptococcus pneumoniae is a bacterium that causes a range of diseases, including pneumonia, ear and sinus infections, and meningitis. Hundreds of millions of illnesses and deaths have been prevented due to vaccines that eradicated smallpox and significantly reduced polio and measles infections. However, some misunderstanding remains regarding how vaccines are made, and why some scary-sounding ingredients [PDF] are included in the manufacturing process.

The production of our vaccines has greatly evolved since the early days, when vaccination was potentially dangerous. Inoculating an individual with ground-up smallpox scabs usually led to a mild infection (called "variolation"), and protected them from acquiring the disease the "regular" way (via the air). But there was always a chance the infection could still be severe. When Edward Jenner introduced the first true vaccination with cowpox, protection from smallpox became safer, but there were still issues: The cowpox material could be contaminated with other germs, and sometimes was transmitted from one vaccinated person to another, leading to the inadvertent spread of blood-borne pathogens. We’ve come far in the last 200 years.

There are different kinds of vaccines, and each requires different processes to move from the laboratory to your physician's office. The key to all of them is production of one or more antigens—the portion of the microbe that triggers a host immune response.

LIVE ATTENUATED VACCINES AND DEAD, "INACTIVATED" VACCINES

There are several methods to produce antigens. One common technique is to grow a virus in what's called a cell culture. Typically grown in large vats called bioreactors, living cells are inoculated with a virus and placed in a liquid growth medium that contains nutrients—proteins, amino acids, carbohydrates, essential minerals—that help the virus grow in the cells, producing thousands of copies of itself in each infected cell. At this stage the virus is also getting its own dose of protective medicine: antibiotics like neomycin or polymyxin B, which prevent bacterial and fungal contamination that could kill the cells serving as hosts for the virus.

Once a virus completes its life cycle in the host cell, the viruses are purified by separating them from the host cells and growth media, which are discarded. This is often done using several different types of filters; the viruses are small and can pass through holes in the filter that trap larger host cells and cell debris.

This is how "live attenuated vaccines" are created. These vaccines contain viruses that have been modified so that they are no longer harmful to humans. Some of them are grown for many generations in cells that aren't human, such as chicken cells, so that they have mutated to no longer cause harm to humans. Others, like the influenza nasal mist, were grown at low temperatures until they lost the ability to replicate in the warmer temperatures of the lungs. Many of these vaccines you were probably given as a child: measles, mumps, rubella ("German measles"), and chickenpox.

Live attenuated vaccines replicate briefly in the body, triggering a strong—and long-lasting—response from your immune system. Because your immune system kicks into high gear at what it perceives to be a major threat, you need fewer doses of the vaccine for protection against these diseases. And unlike the harmful form of the virus, it is extremely unlikely (because they only replicate at low levels) that these vaccines will cause the host to develop the actual disease, or to spread it to other contacts. One exception is the live polio vaccine, which could spread to others and, extremely rarely, caused polio disease (approximately one case of polio from 3 million doses of the virus). For this reason, the live polio virus was discontinued in the United States in 2000.

Scientists use the same growth technique for what are known as "killed" or "inactivated" vaccines, but they add an extra step: viral death. Inactivated viruses are killed, typically via heat treatment or use of a chemical such as formaldehyde, which modifies the virus's proteins and nucleic acids and renders the virus unable to replicate. Inactivated vaccines include Hepatitis A, the injected polio virus, and the flu shot.

A dead virus can't replicate in your body, obviously. This means that the immune response to inactivated vaccines isn't as robust as it is with live attenuated vaccines; replication by the live viruses alerts many different types of your immune cells of a potential invader, while killed vaccines primarily alert only one part of your immune system (your B cells, which produce antibodies). That's why you need more doses to achieve and maintain immunity.

While live attenuated vaccines were the primary way to make vaccines until the 1960s, concerns about potential safety issues, and the difficulty of making them, mean that few are attempting to develop new live attenuated vaccines today.

COMBINATION, BACTERIAL, AND GENETICALLY ENGINEERED VACCINES

Other vaccines aren't made of whole organisms at all, but rather bits and pieces of a microbe. The combination vaccine that protects against diphtheria, pertussis, and tetanus—all at once—is one example. This vaccine is called the DTaP for children, and Tdap for adults. It contains toxins (the proteins that cause disease) from diphtheria, pertussis, and tetanus bacteria that have been inactivated by chemicals. (The toxins are called "toxoids" once inactivated.) This protects the host—a.k.a. you, potentially—from developing clinical diphtheria and tetanus disease, even if you are exposed to the microorganisms. (Some viruses have toxins—Ebola appears to, for example—but they're not the key antigens, so they're not used for our current vaccines.)

As they do when developing live attenuated or inactivated vaccines, scientists who create these bacterial vaccines need some target bacteria to culture. But because the bacteria don't need a host cell to grow, they can be produced in simple nutrient broths by vaccine manufacturers. The toxins are then separated from the rest of the bacteria and growth media and inactivated for use as vaccines.

Similarly, some vaccines contain just a few antigens from a bacterial species. Vaccines for Streptococcus pneumoniae, Haemophilus influenzae type B, and Neisseria meningitidis all use sugars that are found on the outer part of the bacteria as antigens. These sugars are purified from the bacteria and then bound to another protein to enhance the immune response. The protein helps to recruit T cells in addition to B cells and create a more robust reaction.

Finally, we can also use genetic engineering to produce vaccines. We do this for Hepatitis B, a virus that can cause severe liver disease and liver cancer. The vaccine for it consists of a single antigen: the hepatitis B surface antigen, which is a protein on the outside of the virus. The gene that makes this antigen is inserted into yeast cells; these cells can then be grown in a medium similar to bacteria and without the need for cell culture. The hepatitis B surface antigen is then separated from the yeast and serves as the primary vaccine component.

OTHER INGREDIENTS IN VACCINES (AND WHY THEY'RE THERE)

Once you have the live or killed viruses, or purified antigens, sometimes chemicals need to be added to protect the vaccine or to make it work better. Adjuvants, such as aluminum salts, are a common additive; they help enhance the immune response to some antigens by keeping the antigen in contact with the cells of the immune system for a longer period of time. Vaccines for DTaP/Tdap, meningitis, pneumococcus, and hepatitis B all use aluminum salts as an adjuvant.

Other chemicals may be added as stabilizers, to help keep the vaccine working effectively even in extreme conditions (such as hot temperatures). Stabilizers can include sugars or monosodium glutamate (MSG). Preservatives can be added to prevent microbial growth in the finished product.

For many years, the most common preservative was a compound called thimerosal, which is 50 percent ethylmercury by weight. Ethylmercury doesn't stick around; your body quickly eliminates it via the gut and feces. (This is different from methylmercury, which accumulates in fish and can, at high doses, cause long-lasting damage in humans.) In 2001, thimerosal was removed from the vaccines given in childhood due to consumer concerns, but many studies have demonstrated its safety.

Finally, the vaccine is divided into vials for shipping to physicians, hospitals, public health departments, and some pharmacies. These can be single-dose or multi-dose vials, which can be used for multiple patients as long as they're prepared and stored away from patient treatment areas. Preservatives are important for multi-dose vials: bacteria and fungi are very opportunistic, and multiple uses increase the potential for contamination of the vaccine. This is why thimerosal is still used in some multi-dose influenza vaccines.

Though some of the vaccine ingredients sound worrisome, most of these chemicals are removed during multiple purification steps, and those that remain (such as adjuvants) are necessary for the vaccine's effectiveness, are present in very low levels, and have an excellent track record of safety.

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