Researchers on the trail of a treatment for cancer of the immune system

ScienceDaily (Aug. 22, 2011) — Danish researchers from the University of Copenhagen have become the first in the world to regulate a special receptor or bio-antenna that plays a vital part when the Epstein Barr herpes virus infects us and when this infection appears to be mutating into cancer of the immune system. Using a biochemical blueprint and a tiny bio-molecule the Danish researchers have succeeded in blocking the receptor concerned. This will make it possible to adjust and regulate the memory cells of the immune system.

Infection with Epstein Barr means that the B cells, which are the primary memory cells of the immune system, are hi-jacked.

When the virus has penetrated, researchers observe an excess of a special bio-antenna, a receptor known as EB12, suddenly sprouting from the surface of the B cells. But why they do so remains a mystery.

The receptors are a vital component of the way cells communicate with their surroundings via hormones and other bio-molecules, for example, but in a body consisting of millions of cells and transmitters it can be hard to determine the part each molecule plays.

"It is possible that the large numbers of EB12 receptors could actually be the B cells response to the virus and an attempt to combat the infection. Another possibility is that the EB virus reprogrammes the cell for this explosive growth in the number of EB12 receptors. What we know for certain is that more EB12 receptors assist the B cell infected by the EB virus to multiply more rapidly thus spreading the infection faster," says postdoc Tau Benned-Jensen from the Faculty of Health Sciences, University of Copenhagen.

The Epstein Barr virus can cause cancer

No fewer than 95 per cent of us carry the Epstein Barr Herpes virus.

We often encounter it as kids and it is normally harmless. Are we infected later in life EB virus may cause mononucleosis, and it seems to play a part in some forms of cancer, just as HPV affects the risk of cervical cancer. But we have no drugs to combat the Epstein Barr virus, and no vaccines for it.

"Under normal circumstances our immune systems can keep the EB virus infection in a latent state and a truce or stand-off may arise between the immune system and the virus," explains Mette Rosenkilde, professor of pharmacology at the Department of Neuroscience and Pharmacology, University of Copenhagen.

"We cannot dispense with the infection and we carry it all life long, but to most of us it is harmless. For people whose immune systems do not function due to disease or because they are suppressed by drugs in conjunction with organ transplants it is a very different matter. Now the Epstein Barr virus is suddenly free to reproduce so uninhibitedly and dramatically that it may lead to cancer," says Mette Rosenkilde.

The first step on the road to solving the EB12-puzzle

While researchers know that the B cell EB12 receptors play a part when the cell visits the lymph glands, the immune system's Central Station, we have not yet explained the exact role of the receptor.

So the Danish researchers started by mapping the bio-antenna molecule by molecule and then, as the first in the world, they made a blueprint of a tiny molecule they thought could bind to the B cell EB12 receptor.

"When we know what receptors react to, it tells us more about the part they play," Mette Rosenkilde explains, "and our tiny molecule, a ligand, blocks the EB12 receptor, preventing it from doing its job."

"In time this block may be able to help transplant patients. If we can restrain EB virus reproduction when the immune system is being medically suppressed, we may well be able to avoid cancer," Tau Benned-Jensen says.

"On the other hand the EP virus also appears to play a part in other immune diseases such as autoimmune disease, where the ability to adjust the immune system would be beneficial," says Mette Rosenkilde.

And shortly after the Danish researchers published their article on their ligand, the first articles appeared about natural substances in the body, which activate the EB12 receptor and direct the B cell to specific areas in the lymph glands.

"Our molecule can inhibit the activation of the new substances, and the next step in our research will be experiments to identify even more biochemical dials to twiddle and to help us develop new drugs," Tau-Benned says.

The discovery has just been published in the Journal of Biological Chemistry.

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Story Source:

The above story is reprinted from materials provided by University of Copenhagen.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

T. Benned-Jensen, C. Smethurst, P. J. Holst, K. R. Page, H. Sauls, B. Sivertsen, T. W. Schwartz, A. Blanchard, R. Jepras, M. M. Rosenkilde. Ligand Modulation of the Epstein-Barr Virus-induced Seven-transmembrane Receptor EBI2: IDENTIFICATION OF A POTENT AND EFFICACIOUS INVERSE AGONIST. Journal of Biological Chemistry, 2011; 286 (33): 29292 DOI: 10.1074/jbc.M110.196345

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here

Researchers on the trail of a treatment for cancer of the immune system

ScienceDaily (Aug. 19, 2011) — Danish researchers from the University of Copenhagen have become the first in the world to regulate a special receptor or bio-antenna that plays a vital part when the Epstein Barr herpes virus infects us and when this infection appears to be mutating into cancer of the immune system. Using a biochemical blueprint and a tiny bio-molecule the Danish researchers have succeeded in blocking the receptor concerned. This will make it possible to adjust and regulate the memory cells of the immune system.

Infection with Epstein Barr means that the B cells, which are the primary memory cells of the immune system, are hi-jacked.

When the virus has penetrated, researchers observe an excess of a special bio-antenna, a receptor known as EB12, suddenly sprouting from the surface of the B cells. But why they do so remains a mystery.

The receptors are a vital component of the way cells communicate with their surroundings via hormones and other bio-molecules, for example, but in a body consisting of millions of cells and transmitters it can be hard to determine the part each molecule plays.

"It is possible that the large numbers of EB12 receptors could actually be the B cells response to the virus and an attempt to combat the infection. Another possibility is that the EB virus reprogrammes the cell for this explosive growth in the number of EB12 receptors. What we know for certain is that more EB12 receptors assist the B cell infected by the EB virus to multiply more rapidly thus spreading the infection faster," says postdoc Tau Benned-Jensen from the Faculty of Health Sciences, University of Copenhagen.

The Epstein Barr virus can cause cancer

No fewer than 95 per cent of us carry the Epstein Barr Herpes virus.

We often encounter it as kids and it is normally harmless. Are we infected later in life EB virus may cause mononucleosis, and it seems to play a part in some forms of cancer, just as HPV affects the risk of cervical cancer. But we have no drugs to combat the Epstein Barr virus, and no vaccines for it.

"Under normal circumstances our immune systems can keep the EB virus infection in a latent state and a truce or stand-off may arise between the immune system and the virus," explains Mette Rosenkilde, professor of pharmacology at the Department of Neuroscience and Pharmacology, University of Copenhagen.

"We cannot dispense with the infection and we carry it all life long, but to most of us it is harmless. For people whose immune systems do not function due to disease or because they are suppressed by drugs in conjunction with organ transplants it is a very different matter. Now the Epstein Barr virus is suddenly free to reproduce so uninhibitedly and dramatically that it may lead to cancer," says Mette Rosenkilde.

The first step on the road to solving the EB12-puzzle

While researchers know that the B cell EB12 receptors play a part when the cell visits the lymph glands, the immune system's Central Station, we have not yet explained the exact role of the receptor.

So the Danish researchers started by mapping the bio-antenna molecule by molecule and then, as the first in the world, they made a blueprint of a tiny molecule they thought could bind to the B cell EB12 receptor.

"When we know what receptors react to, it tells us more about the part they play," Mette Rosenkilde explains, "and our tiny molecule, a ligand, blocks the EB12 receptor, preventing it from doing its job."

"In time this block may be able to help transplant patients. If we can restrain EB virus reproduction when the immune system is being medically suppressed, we may well be able to avoid cancer," Tau Benned-Jensen says.

"On the other hand the EP virus also appears to play a part in other immune diseases such as autoimmune disease, where the ability to adjust the immune system would be beneficial," says Mette Rosenkilde.

And shortly after the Danish researchers published their article on their ligand, the first articles appeared about natural substances in the body, which activate the EB12 receptor and direct the B cell to specific areas in the lymph glands.

"Our molecule can inhibit the activation of the new substances, and the next step in our research will be experiments to identify even more biochemical dials to twiddle and to help us develop new drugs," Tau-Benned says.

The discovery has just been published in the Journal of Biological Chemistry.

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

Story Source:

The above story is reprinted from materials provided by University of Copenhagen.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

T. Benned-Jensen, C. Smethurst, P. J. Holst, K. R. Page, H. Sauls, B. Sivertsen, T. W. Schwartz, A. Blanchard, R. Jepras, M. M. Rosenkilde. Ligand Modulation of the Epstein-Barr Virus-induced Seven-transmembrane Receptor EBI2: IDENTIFICATION OF A POTENT AND EFFICACIOUS INVERSE AGONIST. Journal of Biological Chemistry, 2011; 286 (33): 29292 DOI: 10.1074/jbc.M110.196345

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here

Potential Herpes Vaccine Disappoints Researchers

WEDNESDAY, Jan. 4 (HealthDay News) -- A potential vaccine for genital herpes has shown only limited effectiveness in thwarting one type of the sexually transmitted virus and no ability to stop a second type from spreading, a new study shows.

A group of American and Canadian researchers conducted a randomized trial on more than 8,300 women aged 18 to 30 who tested negative for both forms of the herpes simplex virus, known as HSV-1 and HSV-2. Half of the women were given the experimental vaccine while the other half were given the hepatitis A vaccine.

The experimental vaccine was 58 percent effective at preventing genital disease stemming from HSV-1, but completely ineffective against HSV-2.

"We were disappointed it did not meet the primary [goal], which was protection against all types of genital herpes," said study author Dr. Robert B. Belshe, a professor of medicine, pediatrics and molecular microbiology at Saint Louis University. "Herpes is a complex organism and has ways of escaping the immune system, so we have to figure out a way of overcoming those mechanisms."

The study is published Jan. 5 in the New England Journal of Medicine.

Genital herpes affects about 16 percent of Americans aged 14 to 49, according to the U.S. Centers for Disease Control and Prevention. Both types of the virus are released from their resulting sores but can also be transmitted between outbreaks, and the infection is potentially fatal in newborns who acquire it from their mothers during birth.

Fifty clinical sites in both the United States and Canada followed the women -- who reported their own sexual risk behaviors -- between 2003 and 2007. A heightened risk for HSV-1 infection was associated with six or more lifetime sexual partners and more than one partner in the previous 12 months, while those who were 23 or older were less likely to contract HSV-1 than those between 18 and 22.

Factors not associated with an increased likelihood of HSV-1 included race, condom use, oral sex, a history of any sexually transmitted infection or ever having a partner with herpes. Men weren't tested in this study, though prior research showed investigational herpes vaccines to be ineffective in men and HSV-1 positive women.

"I was very disappointed there wasn't more of a benefit," said Dr. Bruce Hirsch, an attending physician in infectious diseases at North Shore University Hospital in Manhasset, N.Y., who wasn't involved in the study. "I think we're asking that a vaccine provide better immunity than an actual infection provides. I'm concerned if we'll ever find a vaccine effective for HSV-2."

"I think what we tell patients is ... there are antiviral medications that can make a difference and can give people comfort, and the availability of treatment is encouraging," he added.

While other potential vaccines are in the pipeline, Belshe said, the one that works probably needs to be "more complex" than the one recently studied, which contained a single surface protein of the herpes virus. The chicken pox vaccine, which has been widely used in the past decade, is a good example of a herpes-related virus that has been brought under control, he said.

"Something like that is what we need to come up with for HSV," he said. "I think this is a very important study, and the result is an incredibly important step in figuring out what will work."

More information

The U.S. Centers for Disease Control and Prevention has more on genital herpes.

View the original article here

Follow-up file: Researcher’s herpes vaccine work meets resistance - State Journal-Register

A Springfield researcher’s development of a vaccine to protect against genital herpes, one of the world’s most common sexually transmitted diseases, has received a skeptical reception from the international scientific community so far, but the researcher is neither surprised nor discouraged.

“Science moves kind of like a glacier down a mountain,” said William Halford, associate professor of medical microbiology, immunology and cell biology at Southern Illinois University School of Medicine. “As far as scientists are concerned, there’s nothing unusual about the rate at which this work has progressed.”

Background

Halford, 43, published the results of his latest discoveries in the August 2010 and March 2011 issues of the scientific journal PLoS ONE. In experiments with mice, he demonstrated almost total protection against herpes with a vaccine involving a live but weakened form of the herpes virus.

Even though other vaccines using live viruses have been popular and effective in protecting against diseases such as chicken pox, polio, measles, mumps and rubella, Halford faces an ideological battle with current scientific philosophy and regulatory agencies before his vaccine can be tested in humans.

That’s because Halford said genetic-engineering techniques available since the 1970s have led to a pervasive view that creating new vaccines with live viruses would be too risky for patients compared with other vaccine-development options.

In Halford’s March paper, he pointed out the recent failure in clinical trials of a genital-herpes vaccine made by GlaxoSmithKline using pieces of protein from a virus — trials that cost the federal government $27.6 million between 2003 and 2009.

“If what you’re saying is that this approach, at the end of the day, really isn’t that good, the people who get money out of that approach for their research are usually not thrilled with you,” he said. “When you’re going against the grain, there’s no clear, well-defined path of how to go against the grain.”

Halford said it will take time to change the minds of scientists who are skeptical of his approach. That skepticism, he said, will influence whether the U.S. Food and Drug Administration eventually allows clinical trials in humans with a weakened live virus.

Halford said his research in mice shows results 100 times better than the GlaxoSmithKline vaccine and much safer than even the polio or chicken pox or MMR vaccines, all of which can be encouraging for non-scientists. But he cautioned that clinical trials for humans are at least 10 years away.

About 1 billion people are carriers of genital herpes worldwide, and 20 million people are infected every year, which means young people have a one in 10 chance of acquiring incurable herpes before they marry.

What’s next

Halford said he is conducting more research at SIU to probe why his vaccine works so well. That data, over time, could lead to acceptance by influential scientists, he said.

“In science, you never change a prevailing belief system with one or two papers,” he said. “It just doesn’t work that way. What you do is you keep publishing on it. As far as scientists are concerned, there’s nothing unusual about the rate with which this work has progressed.”

Dr. Anna Wald, a herpes-vaccine researcher at the University of Washington in Seattle who is not associated with Halford, said it is “great” that Halford is working toward an effective vaccine. But she said good results in mouse research don’t necessarily transfer to clinical trials in humans.

Wald, who helped conduct research connected with the failed GlaxoSmithKline vaccine, also said there are important differences between herpes and viruses that cause diseases for which there are live-virus vaccines.

And she said safety-related concerns — that a weakened virus in a new vaccine could cause debilitating infections in patients — are real.

“Once you give someone a live-virus vaccine, you can’t take it back,” she said.

She didn’t deny, however, that Halford may be onto something with his research.

“He might be right, but I think a lot more work needs to be done before this really turns out to be quite as good as it seems,” Wald said.

Dean Olsen can be reached at 788-1543.

View the original article here

Follow-up file: Researcher’s herpes vaccine work meets resistance

A Springfield researcher’s development of a vaccine to protect against genital herpes, one of the world’s most common sexually transmitted diseases, has received a skeptical reception from the international scientific community so far, but the researcher is neither surprised nor discouraged.

“Science moves kind of like a glacier down a mountain,” said William Halford, associate professor of medical microbiology, immunology and cell biology at Southern Illinois University School of Medicine. “As far as scientists are concerned, there’s nothing unusual about the rate at which this work has progressed.”

Background

Halford, 43, published the results of his latest discoveries in the August 2010 and March 2011 issues of the scientific journal PLoS ONE. In experiments with mice, he demonstrated almost total protection against herpes with a vaccine involving a live but weakened form of the herpes virus.

Even though other vaccines using live viruses have been popular and effective in protecting against diseases such as chicken pox, polio, measles, mumps and rubella, Halford faces an ideological battle with current scientific philosophy and regulatory agencies before his vaccine can be tested in humans.

That’s because Halford said genetic-engineering techniques available since the 1970s have led to a pervasive view that creating new vaccines with live viruses would be too risky for patients compared with other vaccine-development options.

In Halford’s March paper, he pointed out the recent failure in clinical trials of a genital-herpes vaccine made by GlaxoSmithKline using pieces of protein from a virus — trials that cost the federal government $27.6 million between 2003 and 2009.

“If what you’re saying is that this approach, at the end of the day, really isn’t that good, the people who get money out of that approach for their research are usually not thrilled with you,” he said. “When you’re going against the grain, there’s no clear, well-defined path of how to go against the grain.”

Halford said it will take time to change the minds of scientists who are skeptical of his approach. That skepticism, he said, will influence whether the U.S. Food and Drug Administration eventually allows clinical trials in humans with a weakened live virus.

Halford said his research in mice shows results 100 times better than the GlaxoSmithKline vaccine and much safer than even the polio or chicken pox or MMR vaccines, all of which can be encouraging for non-scientists. But he cautioned that clinical trials for humans are at least 10 years away.

About 1 billion people are carriers of genital herpes worldwide, and 20 million people are infected every year, which means young people have a one in 10 chance of acquiring incurable herpes before they marry.

What’s next

Halford said he is conducting more research at SIU to probe why his vaccine works so well. That data, over time, could lead to acceptance by influential scientists, he said.

“In science, you never change a prevailing belief system with one or two papers,” he said. “It just doesn’t work that way. What you do is you keep publishing on it. As far as scientists are concerned, there’s nothing unusual about the rate with which this work has progressed.”

Dr. Anna Wald, a herpes-vaccine researcher at the University of Washington in Seattle who is not associated with Halford, said it is “great” that Halford is working toward an effective vaccine. But she said good results in mouse research don’t necessarily transfer to clinical trials in humans.

Wald, who helped conduct research connected with the failed GlaxoSmithKline vaccine, also said there are important differences between herpes and viruses that cause diseases for which there are live-virus vaccines.

And she said safety-related concerns — that a weakened virus in a new vaccine could cause debilitating infections in patients — are real.

“Once you give someone a live-virus vaccine, you can’t take it back,” she said.

She didn’t deny, however, that Halford may be onto something with his research.

“He might be right, but I think a lot more work needs to be done before this really turns out to be quite as good as it seems,” Wald said.

Dean Olsen can be reached at 788-1543.

View the original article here