Allergies are the result of a milder type of internal combat in which the body turns against itself.
When injected into animals, Bachmann’s virus-bacteria hybrid induces a strong antibody response that his company, Cytos Biotechnology, is exploiting to design vaccines against two common inflammatory disorders. Bachmann has had similar success with an asthma vaccine that uses the same virus-bacteria combination.
Some of the new therapeutic vaccines are actually designed to attack the body, albeit in a selective way. Part of the problem may be that an overly aggressive immune attack on artery-clogging plaque can worsen the situation, says Prediman Shah, director of cardiology at Cedars-Sinai Medical Center in Los Angeles.
Shah and his colleagues expect to complete their animal studies by the end of the year and then plan to ask the FDA for permission to launch human trials.
Vaccinating against one of the body’s own hormones seems counterintuitive, or even dangerous.
After trying several biochemical configurations, Zorrilla and colleague Kim Janda hit on one in 2006 that caused immunized mice to lose weight. Efforts to produce anti-addiction vaccines began in the 1970s, but those currently in clinical trials trace back to newer research from the mid-1990s, when Barbara Fox, then an immunologist at ImmuLogic Pharmaceutical Corporation, helped develop a cocaine vaccine. In lab animals the vaccine prompted the immune system to produce antibodies custom-tailored to attach to cocaine molecules. Fox’s vaccine has been sustained and improved by psychiatrist Thomas Kosten at Baylor College of Medicine in Houston. What’s more, the urine tests used to verify abstinence revealed that several users had tried to thwart the vaccine by overdosing. Kosten is also researching vaccines for methamphetamines and opiates, which are among several anti-addiction shots that have the keen interest of the National Institute on Drug Abuse, says NIDA director Nora Volkow, a research psychiatrist who has used brain imaging to investigate the addictive properties of drugs. It is too soon to know how long these vaccines will last and whether they will prevent addicts from switching to other drugs.
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If you are always sneezing in December you might think it's just a common cold but you could be suffering from Christmas tree syndrome. Around 35 per cent of people in the UK suffer from an increase of hay fever symptoms at Christmas.
The English physician knew that dairymaids who contracted cowpox, a comparatively mild skin disease, became immune to the much deadlier smallpox, which at the time killed 400,000 Europeans a year. Preventive vaccines work by introducing harmless microbial chemical markers, known as antigens, which resemble the markers on living microbes. They are exploiting a growing understanding of the immune system to develop therapeutic vaccines: ones aimed not at preventing infection but at rooting out established disease or even changing how the body functions. His research built on the insights of 19th-century surgeon and cancer researcher William Coley, who noticed that for then unknown reasons, postoperative cancer patients with severe bacterial infections often experienced complete remission.
In autoimmune disease, the opposite problem occurs: For reasons still unclear, cells of the immune system mistakenly turn against healthy tissues such as insulin-making pancreatic beta cells (causing juvenile diabetes) or the fatty sheaths that protect nerves (multiple sclerosis).
This biosynthetic hybrid stimulates the development of weak T regs into killer T cells that destroy the immune cells directing the autoimmune attack. Allergy treatments that involve repeated injections of minute amounts of allergens such as pollen, mites, and mold have been around for nearly a century. Thereafter, when the T regs encounter their associated allergens, they respond by secreting inflammation-calming cytokines.
In 2009 Cytos reported the results of a placebo-controlled study with 299 patients allergic to dust mites.
In clinical trials with moderately asthmatic patients who were on chronic steroid treatment, the vaccine has proved just as effective as steroids at keeping asthma at bay.
A new experimental heart-disease vaccine takes aim at unwanted biochemicals within the body, specifically low-density lipoprotein (LDL), better known as bad cholesterol. In the early stages of cholesterol buildup, the immune system removes LDL from artery walls with a relatively gentle antibody-clearing response. They have found they can manipulate the desired immune response by varying which piece of the ldl molecule they include in their vaccine. Zorrilla’s experimental antiobesity vaccine consists of ghrelin molecules chemically linked to hemocyanin, a protein extracted from the keyhole limpet marine snail.
The hurdle, she explains, was to get the immune system to register and attack the small, relatively uncomplicated cocaine molecule rather than the complex biological proteins typically found on microbes. Once bonded, the antibodies make the cocaine molecules too large to slip through the tight blood-brain barrier.
In 2009 Kosten reported the results of a clinical trial with 115 cocaine addicts, half of whom received the vaccine.
NicVAX, an antismoking vaccine that recently received $10 million in funding from NIDA, is in large clinical trials under the auspices of its maker, Nabi Biopharmaceuticals.
But NIDA is embracing the approach and is now researching a vaccine against heroin, the use of which is a vector for HIV transmission in many countries. Jenner hoped the fluid from the cowpox lesion would somehow inoculate the boy against the smallpox scourge.
The antigens train the immune system to recognize and destroy those microbes should they ever appear in the body. In the spring of last year, the FDA approved Provenge, a vaccine that beats back prostate cancer and is the first of the new generation of therapeutic vaccines to go into widespread use. Based at the Cancer Research Institute in New York, Old is the director of the Cancer Vaccine Collaborative, an international program dedicated to fighting cancer from the inside out. In 1891 Coley took the first steps toward cancer immunology when he began intentionally injecting late-stage bone cancer patients with Streptococcus bacteria, which cause strep throat.
In essence, he says, weak T regs can mature into killer T cells that weed out other immune cells mounting attacks on healthy tissues.
Until recently, scientists did not know how such shots worked, simply that they did—at least in a significant percentage of patients. Equipped with this deeper understanding, researchers are trying to make allergy vaccines safer and more effective by designing them to micromanage the allergic immune response. Each subject received six weekly injections with either a placebo or one of two doses of active vaccine. When large quantities of LDL cholesterol circulate through the bloodstream, it can be deposited on artery walls, leading to a buildup of plaque and triggering inflammation.
But if the plaque buildup continues, the immune response may escalate into overaggressive inflammation that further damages the arteries and clogs them with bits of plaque and dead immune cells.
They have also discovered the vaccine lowers blood pressure in mice and protects against the rupture of aneurysms. He points to the disastrous results of a small patient trial using an experimental Alzheimer’s ?vaccine, a related type of therapeutic vaccine. In particular, the researchers must ensure that their vaccine does not result in an autoimmune response to cells that produce ghrelin, which could trigger severe swelling and inflammation. The vaccine generates antibodies to nicotine by linking the addictive molecule to an inactivated bacterial toxin. But in a pilot study conducted on heavy smokers, 24 percent of those who received the NicVAX vaccine were smoke free for the last two months of the six-month study—double the quit rate of those who received placebo shots.
By injecting cowpox antigens into his patients’ bloodstream, for instance, Jenner primed their immune systems to attack the similar smallpox virus. One promising approach boosts T-regulatory cells, or T regs, a recently discovered subgroup of the white blood cells known as T cells. It restored normal blood sugar and insulin levels in animals that already had diabetes and prevented or slowed its onset in young mice that had not yet developed the disease. But these allergy shots must be given at least once a week for months and then at least monthly for three to five years. One way to do that, Swiss immunologist Martin Bachmann has found, is to mimic a microbial infection.
At the end of the trial, those who received the high-dose vaccine scored an average of 39 percent lower on symptoms and medication use than did those who got the dummy shots.
Anti-cholesterol vaccines that encourage the immune system to attack LDL have been in the research pipeline for decades, but early attempts produced mixed results in animals.
In theory, the response to a vaccine combining ghrelin and hemocyanin should clear ghrelin from the bloodstream.
As with the cocaine vaccine, the resulting antibodies do not clear nicotine from the blood so much as stick to it, creating a chemical complex too large to migrate into the brain. Among those who developed antibodies to nicotine but were not able to abstain from smoking, the number of cigarettes they smoked dropped significantly. A 2010 survey by the market analysis firm BCC Research identified 113 therapeutic vaccines in development, many already in human trials. He then tried injecting a combination of heat-killed bacteria, a mixture that became known as Coley’s toxin. The team is now readying the vaccine for human trials and is designing related vaccines to treat other autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. They work best against mild respiratory allergies, such as hay fever, but generally can’t be used to counteract severe allergies to certain foods or drugs because of the danger of triggering anaphylaxis, a life-threatening immune reaction.
He has taken DNA from Mycobacterium tuberculosis and slipped it into synthetic protein capsules virtually identical to those produced by viruses. In 1999 scientists published spectacular results from a study in which a vaccine cured the mouse equivalent of Alzheimer’s.
These patients were cocaine-free at 45 percent of their follow-up exams two to four months after receiving the vaccine. The vaccine contained bits of beta-amyloid protein and directed an immune attack against them. This spurs the immune system to create more cytokine-producing T regs and suppresses the body’s allergic response. When the vaccine was rushed into clinical trials, however, 18 of the 298 participating Alzheimer’s patients developed life-?threatening brain inflammation. Nevertheless, he became fascinated with Coley’s promising results, especially after hearing reports of mouse tumors shrinking after injections of zymosan, a yeast extract.
Tumors in those animals continued to grow for close to two weeks after the injections but then started to disappear.“Clearly the zymosan was not killing the tumors directly,” Old says. Years later, autopsies showed that the vaccine had indeed cleared amyloid plaque from the volunteers’ brains, but the associated inflammation had killed tissue elsewhere in the brain.
In the process he identified one of the first recognized cytokines, or immune signaling molecules.
Cytokines direct the biochemical conversation that immune cells use to coordinate their activities. Old’s insights suggested that Coley’s toxin worked because it tricked the body into releasing a flood of cytokines by exposing the immune system to what seemed like an enormous bacterial attack.
The cytokines then directed an immune response to the bacteria, an onslaught that also killed cancer cells.Many of the cancer vaccines in development today tap into our current understanding of how dozens of these cytokines help coordinate an effective cancer-clearing response.
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