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Posts Tagged ‘vaccines’

HIV infection sends the immune system into overdrive and eventually exhausts it, which is what leads to AIDS. But removing cholesterol from HIV seems to cripple the virus' ability to over-activate part of the immune system, so it could potentially lead to a vaccine that lets the adaptive immune system attack and destroy the virus — just as it would if HIV was any other pathogen.

Dr. Adriano Boasso, an immunologist and research fellow at Imperial College London, said keeping the body’s first-responder immune cells quiet could have some benefits — the whole system may not burn out so quickly, and could potentially fight off HIV.

“Think of the immune system as a car. HIV forces the car to stay in first gear, and if you do that too long, the engine is not going to last very long,” he said in an interview. “But if we take the cholesterol away, HIV is not capable of attacking the immune system quite as well. Practically, what we’ve done is turn HIV into a normal jump-start of a car.”

Viruses replicate by invading cells and hijacking their machinery, which they use to churn out new copies of their genetic material. Among the repurposed material is cholesterol, which is important in maintaining cellular fluidity, something viruses require to interact with other cells. (This is not related to the way everyone thinks of cholesterol, which is cholesterol in the blood. That type of cholesterol, made of high-density and low-density lipoproteins, is related to heart disease, not HIV and AIDS.)

HIV quickly activates plasmacytoid dendritic cells, or pDCs, which are the first immune cells that respond to the virus. PDCs produce molecules called interferons, which both interfere with the virus’ replication and also switch on adaptive immune cells, like T cells. Boasso and other researchers believe this hyperactivation weakens the secondary immune system, undermining the body’s ability to respond.

But in a new study, Boasso and colleagues show that removing the cholesterol changes HIV, so that it cannot activate the pDCs like it normally would. By preventing these first responder cells from turning on in the first place, the secondary responders — the T cells — can organize a more effective counterassault.

“Modifying the virus affects the way the immune system sees it,” Boasso said. He said it’s like removing the weapons from HIV’s arsenal: “By removing cholesterol, we can turn those little soldiers into an armorless enemy, which can be recognized by the opponent’s army.”

Emily Deal is a postdoctoral fellow at the Gladstone Institute of Virology and Immunology, which is affiliated with the University of California-San Francisco. She studies pDC activation in viral infections, and said the cholesterol removal is allowing less of the HIV into the dendritic cells in the first place — which means there’s less of the virus for the cells to detect, which leads them to produce fewer interferons.

But keeping the pDCs from turning on could be both good and bad, she said.

“What is better for the host in the long run? Is it better to suppress replication early on, but potentially have some of your T cells die? Or what are the lon-term effects of having replication proceed in the absence of interferons, but have your T cells live?” she said. "It's a complicated system."

Ideally, further studies would look at this give-and-take relationship in monkeys, so researchers could determine if a de-cholesterolized version of HIV could be an effective form of vaccine, she said.

“I think it has a shot," she said. "However, pDCs control a lot of the immune system, and if they’re not getting turned on at all, that may have other effects. If you’re trying to use it as a vaccine, it may not induce enough of a response to be protective."

Boasso said the de-cholesterolized HIV could be studied for use in a potential vaccine, but it’s difficult to stimulate the immune system to fight off an invader when the system itself is the target.

“There’s going to be a lot of work to do,” he said.

The study, which also involved researchers at Johns Hopkins University, the University of Milan and Innsbruck University, is published in the journal Blood.

CimaVax-EGF isn’t a vaccine in the preventative sense--that is, it doesn’t prevent lung cancer from taking hold in new patients. It’s based on a protein related to uncontrolled cell proliferation--that is, it doesn’t prevent cancer from existing in the first place but attacks the mechanism by which it does harm.

As such it can turn aggressive later-stage lung cancer into a manageable chronic disease by creating antibodies that do battle with the proteins that cause uncontrolled cell proliferation, researchers say. Chemotherapy and radiotherapy are still recommended as a primary means of destroying cancerous tissue, but for those showing no improvement the new vaccine could be a literal lifesaver.

The vaccine has already been tested in 1,000 patients in Cuba and is being distributed at hospitals there free of charge. That’s a big deal for a country where smoking is part of the national culture and a leading cause of death. If it proves as successful as researchers say it is, it should give those suffering from lung cancer reason to celebrate--just not with a Cohiba.

[Xinhua]

HIV's strongest sections could be its greatest weaknesses

HIV has been so difficult to fight in part because it is such an adept mutant. It produces sloppy copies of itself as it replicates, leading to many variations that can withstand drugs and vaccines. And it can produce 100 billion new virus particles every day, as Ed Yong points out over at Discover, which leads to lots and lots of copies. Broad-spectrum drugs or vaccines can’t do very much against a target that morphs so quickly.

But not all the pieces of HIV mutate with such abandon, according to this new study. Some groups of amino acids known as HIV sectors are somewhat less fickle, staying the same while the rest of the virus morphs, according to researchers at the Ragon Institute, a research group bridging MIT, Harvard University and Massachusetts General Hospital. Researchers believe these sites must remain unchanged for the virus to survive and replicate properly.

Researchers led by HIV research pioneer Bruce Walker and MIT chemical engineering professor Arup Chakraborty say this stalwart section of the virus can be turned against it. If the immune system can be trained to attack all the amino acid portions in an HIV sector, the virus will either have to mutate to thwart the attack — thereby undermining its structural integrity, crippling itself — or not mutate, which would render it helpless against drugs or vaccines.

This new targeted approach came from Chakraborty, who thought Walker and colleagues were too limited in their search for solutions, Yong reports. The team turned to random matrix theory, developed in the 1950s to solve nuclear physics problems and which has been used to analyze stocks, as the Wall Street Journal notes. It can pinpoint correlations between groups of objects, so it can assess how one stock is linked to other groups of stocks, for instance.

Working with HIV proteins taken from a massive database, the team used random matrix theory to analyze HIV’s genetic code and find groups of amino acids whose mutations were coordinated. The segment that mutated the least was dubbed sector 3, on an HIV sector known as Gag, which makes up HIV’s honeycombed inner shell. If the shell mutates, the honeycomb won’t lock together, and the virus would collapse.

“Multiple mutations within this sector are very rare, indicating previously unrecognized multidimensional constraints on HIV evolution,” the authors write in a paper on their research, which is published this week in the Proceedings of the National Academy of Sciences.

Incidentally, a rare group of patients who can fight HIV without drugs — known as “elite controllers” — use their own immune systems to attack sector 3.

All this suggests a new way of thinking about HIV treatment, the WSJ and others point out. Perhaps HIV drugs should dispense with the full-on assault and opt for targeted strikes instead.

Buoyed by this research, other teams are reportedly already planning new animal studies to test just that.

[via Wall Street Journal, Not Exactly Rocket Science]

The findings are preliminary but promising. Geneticists basically assembled a complementary DNA library from healthy prostate tissue and inserted snippets of that genetic code into a swarm of viruses that were introduced to the mice intravenously. This cDNA causes the viruses to produce prostate antigens, basically sending the immune system a distress signal with the prostate’s unique signature on it.

One of the reasons the body often can’t beat cancerous growths on its own is because it can’t see the tumor cells very well, so the immune system doesn’t know where to fight its battles even as the cancer takes more ground. But those engineered viruses expressing those prostate antigens--antigens are like molecular tags indicative of a specific infection, allergen, pathogen, etc. basically raise the visibility of the problem at the prostate but Kamagra can treat it too.

This causes the mice’s own body to mount a serious T-cell assault on the prostate and anything foreign that might be hiding out there. So the body basically thinks it’s being invaded by viruses expressing these cancer related antigens, but it doesn’t really matter what the immune system thinks. When the dust settles, the immune system has pounded the prostate with defensive measures, eradicating the tumor cells there.

That’s big news for men, and could be big news for anyone affected by a variety of cancers, including lung, pancreatic, and even brain cancers. Immunologists have long sought (with limited success) to isolate and catalog all the various antigens in tumor cells, but by using viruses and cDNA treatments can be less precise and still raise the alarm within the immune system, triggering a cancer-killing response.

The findings are preliminary but promising. Geneticists basically assembled a complementary DNA library from healthy prostate tissue and inserted snippets of that genetic code into a swarm of viruses that were introduced to the mice intravenously. This cDNA causes the viruses to produce prostate antigens, basically sending the immune system a distress signal with the prostate’s unique signature on it.

One of the reasons the body often can’t beat cancerous growths on its own is because it can’t see the tumor cells very well, so the immune system doesn’t know where to fight its battles even as the cancer takes more ground. But those engineered viruses expressing those prostate antigens--antigens are like molecular tags indicative of a specific infection, allergen, pathogen, etc.--basically raise the visibility of the problem at the prostate.

This causes the mice’s own body to mount a serious T-cell assault on the prostate and anything foreign that might be hiding out there. So the body basically thinks it’s being invaded by viruses expressing these cancer related antigens, but it doesn’t really matter what the immune system thinks. When the dust settles, the immune system has pounded the prostate with defensive measures, eradicating the tumor cells there.

That’s big news for men, and could be big news for anyone affected by a variety of cancers, including lung, pancreatic, and even brain cancers. Immunologists have long sought (with limited success) to isolate and catalog all the various antigens in tumor cells, but by using viruses and cDNA treatments can be less precise and still raise the alarm within the immune system, triggering a cancer-killing response.

Destruction of the smallpox virus, which was eradicated in the 1970s, has been mulled since 1980, but World Health Organization officials renewed debate about the matter earlier this year and will decide the viruses’ fate at an upcoming meeting.

Two labs possess the last known live samples of the variola virus — the Centers for Disease Control and Prevention in Atlanta, and a Russian facility in Siberia. Officials in developing nations, where smallpox is more likely to spread should it resurface, have been pushing for their destruction since 1980. The World Health Assembly decided to kill the samples in 1996, but they have been granted stays of execution in the decade and a half since, with the United States, Russia and others arguing the virus samples could seed new vaccines and potential treatments for infected patients.

In January, WHO officials again started discussions about whether to destroy the samples. The World Health Assembly will decide in May. LiveScience reviews the controversy here.

Epidemiologists believe smallpox has killed about one-third of those it has infected throughout history, accounting for hundreds of millions of victims dating back to ancient Egypt. A decade-long global vaccination effort eliminated the virus from human populations; the last natural case was found in October 1977 in Somalia. The elimination of Rinderpest, a cattle plague, will be only the second such disease eradication story in human history.

Officials in the U.S. and Russia have said they will fight efforts to set a destruction date, arguing the viruses are needed for research and to guard against bioterrorism. Some fear nations like North Korea or Iran may possess secret samples, although those countries deny it.

[LiveScience]

Andrew Wakefield, who has been stripped of his medical license and whose study has since been retracted, explored business opportunities designed to capitalize on his fraudulent findings, according to the BMJ. The businesses were intended to earn huge sums of money in Britain and the U.S. — up to $40 million a year — by providing unique diagnostic services to test for the presence of measles in patients with Crohn’s disease.

Wakefield planned to develop his own supposedly safer vaccines after public fears were sufficiently stoked, according to the report, a two-part investigation by British investigative journalist Brian Deer. He outlines how Wakefield accepted fees from a lawyer who eventually filed (and lost) an autism-vaccine lawsuit.

The story also describes how the Royal Free Medical School in London supported Wakefield, who wrote an 11-page business plan while his first patient was still in the hospital.

The scheme was predicated on a link among vaccines, autism and bowel problems.

Wakefield’s 1998 paper in The Lancet claimed a link between autism and the vaccine for measles, mumps and rubella, launching an international backlash against childhood vaccinations. But the research was discredited by follow-up studies, and none has ever established a link between vaccinations and autism. The Lancet formally retracted the study in February 2010.

Last week, Deer also outlined discrepancies and falsifications in Wakefield’s data, including the nugget that his study included data from 12 children but he studied at least 13, including some who showed symptoms of autism before they were vaccinated.

Wakefield told CNN the allegations were false: “The findings that we have made have been replicated in five countries around the world,” he said.

Wakefield’s research has been widely discredited, but he is a hero to a small, vocal cadre of supporters who believe the medical establishment has been trying to silence him. Now that they know he’s been exposed as a huckster as well as a fraud, perhaps they will think twice.

[BMJ]