Posts Tagged ‘antibodies’
Experimental “Body Reboot” Drug Begins Trial As Preemptive Preventer Of Diabetes
But a new trial, launched through the National Institutes of Health’s Type 1 Diabetes Trial Net, may change that. Headed by Kevan Herold, M.D., TrialNet Principal Investigator and Professor of Immunobiology and Medicine at Yale University, the – which is currently enrolling -- will test whether a drug called teplizumab might be able to prevent or delay Type 1 in high-risk relatives of people with the disease.
Teplizumab is what’s known as an anti-CD3 monoclonal antibody, a targeted immunosuppressive drug that I wrote about for Popular Science last . I know about teplizumab because I took it myself – after being diagnosed with Type 1 diabetes in 2001 at the age of 22, I enrolled in a study that tested whether teplizumab might preserve some insulin production in people recently diagnosed with the disease. In my case, it worked: nine years out, I was still producing a measurable amount of insulin, which in the normal course of Type 1, doesn’t happen. (I’m going in for a 10-year follow-up at the end of March.)
The results of the trial I participated in, which were published in the New England Journal of Medicine, were exciting to researchers and patients alike. But unfortunately, teplizumab is not a cure. Reversing Type 1 diabetes remains a frustratingly complicated challenge, one that would require not just replacements for the cells that have been destroyed, but a successful override of at least two different immune responses: the tendency to reject foreign tissue (transplanted insulin-producing cells would be rejected just like a transplanted kidney), and the immune reaction that triggered Type 1 to begin with.
Mindful of these challenges, researchers have long sought a way to prevent Type 1 from developing to begin with – and the results of the teplizumab studies (later corroborated by other studies using the same drug), suggested an interesting possibility. Researchers have recently discovered that Type 1 takes a long time to fully develop – autoantibodies against the insulin-producing cells can begin to develop up to 10 years before symptoms appear. Teplizumab is thought to work by shutting off the part of the immune system most responsible for attacking the insulin-producing cells. So what if it were to be given to high-risk people before they developed symptoms? Researchers like Herold hypothesize that a preemptive treatment with teplizumab might prevent those immune cells from attacking in the first place.
For people interested in the study – or simply in finding out their risk -- Trial Net offers a screening test kit, available either by mail or in person, to check for the autoantibodies that lead to Type 1. The screening is free for people 45 years old or younger with a parent, sibling, or child with Type 1 diabetes, as well as for people under 20 who have a niece, nephew, aunt, uncle, grandparent, half-sibling or cousin with the disease. People who test positive may be eligible to participate in the trial; people who test negative for the autoantibodies can be retested annually for free until they turn 18.
It can be a difficult decision to have your family members screened, especially children. But personally, I know that if I’d had the opportunity to be screened, I would have taken it – regardless of whether there were a trial to participate in. Not only could screening help you learn about possible opportunities for prevention and early treatment, but the earlier you catch Type 1, the less likely you are to develop diabetic ketoacidosis, a potentially deadly complication brought on by extremely high blood glucose levels. In my case, I might have caught the symptoms – and started insulin – before I landed in the hospital for a week, bewildered and terrified to be diagnosed with a disease for which I never knew I was at risk.
The results of the Anti-CD3 Prevention Study obviously remain to be seen – previous trials to prevent Type 1 have been disappointments. Still, Herold – who has Type 1 himself – is cautiously optimistic. “There is no other trial in the world that is testing prevention of Type 1 diabetes in this particular group of people,” he says. “It’s the most exciting trial I’ve ever done.”
More information about the trial is available at .
H1N1 Finding Could Lead to Universal Flu Vaccine
The scientists studied a group of nine adult patients who were variously affected by the H1N1 pandemic, some of whom experienced mild illness, others who were hospitalized for severe influenza (some for lengthy periods of time). Blood samples were taken from this group and from that the team isolated white blood cells that had produced antibodies that were effective against the flu virus.
The team then isolate the genes responsible for that antibody production and used them to create more antibodies in culture, resulting in 86 varieties of antibodies. They then turned the antibodies loose on a variety of flu strains. Of the 86 antibodies, five were able to bind with all the seasonal H1N1 strains identified over the last decade, the 1918 “Spanish flu” strain, and even the H5N1 bird flu strain.
These antibodies could lead to a single-injection, lifetime flu vaccine effective against multiple strains of influenza, both new and old. Current vaccinations are required to inoculate against at least one H1N1 strain, but they usually don’t insure against all of them – hence the 2009 strain’s ability to sicken even those who had received their standard seasonal flu shots.
So what’s to stop future influenza strains from circumventing these antibodies? Well, nothing really. But these antibodies were found to bind to the “stalk” region of the virus, a certain protein called haemagglutinin. This part of the virus tends to be rather static in the evolutionary sense, rarely changing as much as other regions over time. By arming the human body with the right kinds of antibodies researchers believe they could provide lifelong protection from most influenza strains, and perhaps even all of them.
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Vaccine Research to Protect the Public From Weaponized Plague Bacteria
Researchers have been working for several years to develop a vaccine for weaponized forms of plague, which is one of the world’s deadliest infectious diseases. It can be cured with antibiotics, but a weaponized form would likely defy drugs. Vaccination efforts have therefore focused on building antibodies, but a recent Army study suggested antibodies alone might not be sufficient.
Now, a team at the New York-based Trudeau Institute say the key might be a cellular messaging system that helps produce a stronger immune response. Cytokines, which are proteins used for intercellular communication, work together with antibodies, according to a new paper by . He says researchers should further examine cytokines’ role in antibody production.
The bacterium Yersinia pestis causes plague, which can take several forms: the best-known type, bubonic plague, infects the lymph nodes. Pneumonic plague affects the lungs and septicemic plague infects the blood. Smiley’s research focuses on pneumonic plague, which would likely be weaponized in an aerosol form.
An antibody-based vaccine would deliberately expose a person to an inactive strain of plague, which stimulates the immune system to build antibodies. The body retains the ability to generate more of these protectors if it’s attacked again.
A few years ago, Army scientists tested a vaccine in two types of primates, and realized that although they both produced similar antibodies, the vaccine worked better in one primate species than in the other. The problem was, scientists didn’t know which primate was more like humans, raising questions as to how we would respond to a vaccine. Smiley’s research group has a new paper in the journal Vaccine that says the two primate species in the study probably produced different amounts of cytokines. Knowledge of the right cytokine mixture could refine efforts to make a vaccine for widespread use.
Plague has been used as a weapon since the Middle Ages, when armies would hurl plague-infested bodies over castle walls. More recently, the U.S., Japan and the former Soviet Union have all studied the use of Y. pestis as a biological warfare agent. The USSR developed an aerosolized form, which would be particularly deadly because plague spreads easily through the air.
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Newly Discovered Antibody Defeats 91 Percent of HIV Strains
One of the antibodies suppresses 91 percent of HIV strains, more than any AIDS antibody ever discovered, according to a report on the findings published in the . The antibodies were discovered in the cells of a 60-year-old African-American gay man whose body produced them naturally. One antibody in particular is substantially different from its precursors, the Science study says.
The antibodies could be tried as a treatment for people already infected with HIV, the WSJ reports. At the very least, they might boost the efficacy of current antiretroviral drugs.
A vaccine for HIV, the virus that causes AIDS, would likely work by activating the body's own ability to produce antibodies that would ward off the disease. The latest discovery is more promising than a trial in Thailand last year in which scientists said an HIV vaccine reduced the chances of infection by just 30 percent. That study had also been plagued with controversy because in one analysis, the results were not statistically significant.
The WSJ says the new discovery -- involving scientists from the National Institutes of Health, Harvard Medical School, Howard Hughes Medical Institute and Columbia University -- is part of a renaissance in HIV vaccine research, which will be in focus later this month in Vienna, home to this year's International AIDS Conference.
It is welcome news for the the 33 million people the United Nations estimated were living with AIDS at the end of 2008.
The WSJ outlines the painstaking method the team used to find the antibody amid the cells of the African-American man, known as Donor 45. First they designed a probe that looks just like a spot on a particular molecule on the cells that HIV infects. Then they used the probe to attract only the antibodies that efficiently attack that spot. They screened 25 million of Donor 45's cells to find just 12 cells that produced the antibodies.
Scientists have already discovered plenty of antibodies that either don't work at all or only work on a couple HIV strains. Last year marked the first time that researchers found "broadly neutralizing antibodies," which knock out many HIV strains. But none of those antibodies neutralized more than about 40 percent of them, the WSJ says. The newest antibody, at 91 percent neutralization, is a marked improvement.
Still, more work needs to be done to ensure the antibodies would activate the immune system to produce natural defenses against AIDS, the study authors say. They suggest three test methods that blend the three new antibodies together -- in raw form to prevent transmission of the virus, such as from mother to child; in a microbicide gel that women or gay men could use before sex to prevent infection; or as a treatment for HIV/AIDS, combined with antiretroviral drugs.
If the scientists can find the right way to stimulate production of the antibodies, they think most people could produce them, the WSJ says.
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Plastic Antibodies Shown to Fight Off Antigens in the Body Just Like the Real Thing
Antibodies are the proteins in our bodies produced by the immune system to recognize and neutralize foreign threats like infections, allergens, viruses and bacteria. These can include things as annoying but benign as plant pollen and dust to food allergens, bee venom, and other toxins. Our body produces antibodies in decent quantities, but in the case of allergies our immune systems can be unequipped to deal with certain antigens, and in other cases – such as a bad infection – our own natural antigens can simply become overwhelmed.
To counter these immune system shortcomings, the researchers took tiny plastic nanoparticles that had previously shown the ability to mimic natural antibodies. They then used a process known as molecular imprinting to stamp the shape of the antigen melittin, the primary toxin in bee venom, onto the antibody. By imprinting tiny antigen-shaped craters into the individual particles, the plastic antibodies were then finely tuned to attach themselves to those antigens in the blood.
The team then dosed a bunch of laboratory mice with lethal doses of melittin followed by an injection of the artificial antibodies. Those mice that received the antibodies showed a far higher survival rate, suggesting that the finely tuned plastic proteins can indeed track down and destroy threats within the living body.
The success of the molecular imprinting process coupled with the heightened survival rate of the mice suggests researchers could tailor a variety of these nanoparticles for use in just about any case where the body relies on antibodies for to fight off threats. That’s a lot of cases, opening the door to a synthetic immune booster that could potentially be used to treat myriad allergies, illnesses and infections.
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