Bird flu shuffle probes viral compatibility

The good news is that packaging signals on the H5 and H7 viral RNA genomes are often incompatible with the H3N2 viruses. But mix and match still occurred at a low level, particularly with Read more

A life consumed by sleep

Nothing he tried had worked. For Sigurjon Jakobsson, the trip to Atlanta with his family was a last-ditch effort to wake up. He had struggled with sleeping excessively for several years before coming from Iceland to see a visionary neurologist, who might have answers. In high school, Sigurjon was a decathlete competing as part of Iceland’s national sports team. But at the age of 16, an increasing need for sleep began to encroach upon his life. Read more

Laughter may be best medicine for brain surgery

Emory neurosurgeons see the technique as a “potentially transformative” way to calm some patients during awake brain surgery, even those who are not especially Read more

Immunology

A Human Vaccine Project?

Emory Vaccine Center director Rafi Ahmed, is a co-author on a recent Science paper advocating a “Human Vaccines Project”. Wayne Koff, chief scientific officer of IAVI (International Aids Vaccine Initiative) is lead author and several other vaccine experts are co-authors.

The idea behind a “Human Vaccine Project” is to combine efforts at developing vaccines for major (but very different) diseases such as influenza, dengue, HIV, hepatitis C, tuberculosis and malaria, with the rationale that what scientists working on those diseases have in common is the Ray Ban outlet challenge of working with the human immune system.

Technology has advanced to the point where whole genome-type approaches can be brought to bear on vaccine problems. The authors cite work by Bali Pulendran’s laboratory on “systems vaccinology” and their analysis of the yellow fever vaccine as an example.

One major puzzle confronting vaccine designers is to coax the immune system into producing broadly neutralizing antibodies against a rapidly mutating virus, whether it is Gafas Ray Ban outlet influenza or HIV. Our own Cynthia Derdeyn has been analyzing this problem through painstaking work following how the immune system pursues a twisting and turning HIV.

An interesting related tidbit:

There are hints that the reverse engineering of vaccines has taken a leap forward in the case of RSV (respiratory syncytial virus): Scientists at Scripps Research Institute have designed vaccine components by computer and have used them to provoke neutralizing antibodies in monkeys.

Also check out Mike King’s feature in Emory Health on HIV vaccine research.

Posted on by Quinn Eastman in Immunology Leave a comment

Detecting clandestine chlamydia

In recent years public health authorities have raised concern that many strains of Chlamydia trachomatis, a bacterium that is the most common cause of sexually transmitted infections around the world, can be missed by conventional genetic tests. A mutation in part of its genomc can make Chlamydia undetectable by the most commonly used tests.

Microfluidic

The Chlamydia tests are performed in a microfluidic cassette platform and data is returned about an hour after sample collection. In comparison, standard tests take a day or longer.

Most infections are asymptomatic but left untreated, Chlamydia infection can lead to pelvic inflammatory disease, infertility and ectopic pregnancy. It is also a Ray Ban online leading cause of blindness in developing countries.

Microbial geneticist Tim Read at Emory has been collaborating with Deborah Dean at Children’s Hospital Oakland and the Massachusetts firm NetBio to develop a fast, accurate and sensitive genetic test for Chlamydia.

“We used tools that were developed initially to answer basic scientific questions,” Read says. “We compared multiple genomes of C. trachomatis to find targets that would work across a broad selection of bacterial strains.”

Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Old drug = new treatment for parasitic skin disease?

A coal-tar dye first produced in the 19th century, gentian violet is available over the counter as an antifungal agent.

Dermatologist Jack Arbiser has been a champion of the inexpensive drug gentian violet for skin diseases. He recently teamed up with collaborators in Brazil to find that gentian violet is active against leishmaniasis, a disfiguring skin disease found in many tropical and subtropical countries.

Caused by protozoan parasites and transmitted by sand flies, leishmaniasis’ most common form produces skin sores but can also affect the nose and mouth and even vital organs. The World Health Organization has identified Kabul, Afghanistan as a world hot spot for leishmaniasis.

In the journal PLOS One, Ana Paula Fernandes and colleagues at the Federal University of Minas Gerais showed that gentian violet and related compounds are active against Leishmania species in animal models.

Conventionallly, therapy for leishmaniasis has involved antimony compounds, but resistance is growing. More recently, clinicians have used the drugs miltefosine and amphotericin against leishmaniasis, but severe side effects have been reported.

“Because it has a http://www.troakley.com/ proven safety record, gentian violet might be a useful treatment that can be used in developing countries as well as by US troops serving in Afghanistan,” Arbiser says.

Arbiser also recently published a case report on the use of gentian violet, in combination with the immune modulator imiquimod, to treat melanoma.

Posted on by Quinn Eastman in Immunology Leave a comment

Emory scientists co-signers of H5N1 flu letter

Emory influenza researchers Richard Compans, Anice Lowen and John Steel are co-signers of a statement announcing the end of a self-imposed moratorium on H5N1 avian flu research.

Last year, an international group of researchers called for the moratorium after public concern over studies of H5N1 transmissibility in ferrets, a model for spread of infection between humans. The group of researchers has now recommended ending the moratorium, citing safeguards and safety review procedures put in place by the National Institutes of Health and authorities in other countries. From the letter published today in Science and Nature:

In January 2012, influenza virus researchers from around the world announced a voluntary pause of 60 days on any research involving highly pathogenic avian influenza H5N1 viruses leading to the generation of viruses that are more transmissible in mammals. We declared a pause to this important research to provide time to explain the public-health benefits cheap oakley of this work, to describe the measures in place to minimize possible risks, and to enable organizations and governments around the world to review their policies (for example on biosafety, biosecurity, oversight, and communication) regarding these experiments.

…Thus, acknowledging that the aims of the voluntary moratorium have been met in some countries and are close to being met in others, we declare an end to the voluntary moratorium on avian flu transmission studies.

Dan Vergano has a more extensive story in USA Today.

Compans is professor of microbiology and immunology at Emory University School of Medicine and scientific director of Emory’s Influenza Pathogenesis and Immunology Research Center. Lowen and Steel are assistant professors of microbiology and immunology at Emory and IPIRC investigators.

Posted on by Quinn Eastman in Immunology Leave a comment

Playing tetherball with HIV

Raise your hand if you played tetherball in grade school. Paul Spearman and his colleagues have a new paper in the journal Cell Host & Microbe probing a protein called “tetherin” that keeps HIV ensnared within cells it is infecting.

The paper includes electron microscopy images that make it possible to imagine a tiny cord attached to a nascent HIV particle within the cell. In these images, we don’t see the tetherin protein directly. However, we do see gold beads, bound to antibodies against the tetherin protein, which indicate where the protein is. The microscopy was performed at Emory’s Robert P. Apkarian Integrated Electron Microscopy Core.

Tetherin is a so-called “restriction factor,” one of several proteins within the cell that interfere with parts of the viral life

The black dots are antibody-linked gold beads, which indicate where the tetherin is. The larger globules are viral capsids.

cycle. Other restriction factors include enzymes that strip the viral RNA or impede the assembly of the viral capsid. Tetherin also interferes with a variety of other viruses such as Ebola.

Some viral proteins such as HIV’s Vpu or Nef fight back against the action of tetherin. Tracking how this kind of arms race has developed can help scientists follow how HIV evolved from similar retroviruses that infect non-human primates. In addition, knowing how tetherin works could be important in efforts to eradicate potential reservoirs of HIV in infected individuals, and in understanding how the virus is transmitted from person to person.

In their paper, first author Hin Chu and Spearman wanted to determine why infection looks different in two different cell types vulnerable to HIV. In T cells, HIV assembly occurs near the membrane, but in macrophages, HIV assembly occurs in an internal compartment.

“The reason that there is a large, internal collection of HIV particles in macrophages is hotly debated,” Spearman explains. “Some see this as a reservoir of virus that is available to spread to other cells, others would say this is a dead-end compartment. We found that the compartment basically goes away when we deplete tetherin, so tetherin is essential to the existence of the virus-containing compartment.”

Chu and his co-workers examined what happened in macrophages when they used a tool called “RNA interference” to turn off the tetherin gene.

Hin Chu

“We found that cell-cell transmission was enhanced when we depleted tetherin. My interpretation is that when tetherin is upregulated in macrophages, viral particles are rapidly internalized and are not transmitted.”

“Another significant finding is that Vpu doesn’t work well in macrophages. If we can determine why it doesn’t work well in this cell type, it will help us understand how Vpu does work so efficiently in other cells such as T cells. Macrophages are one of the most important cell types infected by HIV, so these questions are likely to be very important in how virus spreads and is maintained in infected individuals.”

Spearman is chief research officer for Children’s Healthcare of Atlanta and director of the Children’s Center for Vaccines and Immunology, within the Emory-Children’s Pediatric Research Center. He is also professor and vice chair of research in pediatrics at Emory. Hin Chu is a graduate student in the Microbiology and Molecular Genetics program.

Posted on by Quinn Eastman in Immunology 1 Comment

Present at the creation: immunology from chickens to lampreys

You can get far in biology by asking: “Which came first, the chicken or the egg?” Max Cooper discovered the basis of modern immunology by asking basic questions.

Cooper was selected for the 2012 Dean’s Distinguished Faculty Lecture and Award, and on Thursday evening dazzled an Emory University School of Medicine audience with a tour of his scientific career. He joined the Emory faculty in 2008 as a Georgia Research Alliance Eminent Scholar.

Max Cooper, MD

Cooper’s research on the development of the immune system, much of it undertaken before the era of cloned genes, formed the underpinnings of medical advances ranging from bone marrow transplants to monoclonal antibodies. More recently, his research on lampreys’ divergent immune systems has broadened our picture of how adaptive immunity evolved.

Cooper grew up in Mississippi and was originally trained as a pediatrician, and became interested in inherited disorders that disabled the immune system, leaving children vulnerable to infection. He joined Robert Good’s laboratory at the University of Minnesota, where he began research on immune system development in chickens.

In the early 1960s, Cooper explained, scientists thought that all immune cells developed in one place: the thymus. Working with Good, he showed that there are two lineages of immune cells in chickens: some that develop in the thymus (T cells) and other cells responsible for antibody production, which develop in the bursa of Fabricius (B cells). [On Thursday, he evoked chuckles by noting that a critical discovery that drove his work was published in the journal Poultry Science after being rejected by Science.]

Cooper moved on to the University of Alabama, Birmingham, and there made several discoveries related to how B cells develop. A collaboration with scientists at University College, London led to the identification of the places where B cells develop in mammals: fetal liver and adult bone marrow.

Cooper’s research on lampreys began in Alabama and has continued after he came to Emory in 2008. Primitive lampreys are thought to be an early offshoot on the evolutionary tree, before sharks, the first place where an immune system resembling those of mammals and birds is seen. Lampreys’ immune cells produce “variable lymphocyte receptors” that act like our antibodies, but the molecules look very different in structure. These molecules were eventually crystallized and their structure probed, in collaboration with Ian Wilson in San Diego.

Lampreys have variable lymphocyte receptors, which resemble our antibodies in function but not in structure

Cooper said he set out to figure out “which came first, T cells or B cells?” but ended up discovering something even more profound. He found that lampreys also have two separate types of immune cells, and the finding suggests that the two-arm nature of the immune system may have preceded the appearance of the particular features that mark those cells in evolution.

 

 

 

Posted on by Quinn Eastman in Immunology 1 Comment

Fertility: a new frontier in treating those with HIV

HIV

Not long ago, physicians who treated those with HIV focused only on helping their patients stay well. Today some physicians are also beginning to focus on helping those patients conceive.

“Most of the patients who are now diagnosed with HIV are in their reproductive years, and as many as a third express a desire to have children,” says Emory reproductive endocrinologist Vitaly Kushnir, MD.

This emerging area of treatment has been made possible thanks to the growing effectiveness of a combination of drugs known as Highly Active Antiretroviral Therapy, or HAART, used for years to treat retroviruses, including HIV.

“Now that people with HIV are living longer, fertility and HIV is an emerging area of interest,” says Kushnir. “Several studies have indicated that HIV drugs if given early in the course of the disease can reduce the risk of transmission from an HIV-positive person to an HIV-negative person.”

But researchers and physicians know very little yet about how treatments for HIV, the virus itself, and the comorbidities associated with HIV affect fertility. So, Kushnir and his colleague, Emory pathologist William Lewis, MD, decided it was time to explore existing data on how HIV and its treatment affect fertility, especially in women. Their review paper on the subject appears in the August 2011 issue of Fertility and Sterility.

Because there are safety concerns and legal restrictions on fertility treatments in couples in which one partner is HIV positive and the other is not, treatment options often are limited.

“This is becoming more and more of an issue,” says Kushnir. “It’s probably time for us to have a more open discussion about the access these patients have to fertility treatment. I think the current system probably discourages these patients from pursuing treatments that are a lot safer than trying to get pregnant on their own.”

Posted on by Robin Tricoles in Immunology Leave a comment

Excitement building over potential for universal flu vaccine

Francis Collins, director of the National Institutes of Health, made a splash last week predicting the arrival of a universal flu vaccine in the next five years.

Francis Collins told USA Today he is "guardedly optimistic" about the possibility of long-term vaccination that could replace seasonal flu shots.

His prediction came at the same time as a report in Science identifying an antibody that can protect against several strains of the flu virus. Taking a look at the Science paper, how the scientists found the “super antibody” seems remarkably similar to how Emory’s Jens Wrammert, Rafi Ahmed and colleagues found a similar broadly protective antibody. Their results were published in the Journal of Experimental Medicine in January.

In both cases, the researchers started with someone who had been infected with the 2009 H1N1 swine origin flu virus, sifted through the antibodies that person produced and found some that reacted against several varieties of the flu virus. There must be something special about that 2009 pandemic strain!

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Dispelling confusion about probiotic bacteria

While humans have been consuming fermented foods such as yogurt and kimchi for centuries, a visitor to a modern grocery store can see the recent commercial enthusiasm for adding probiotic bacteria to foods. A recent article in Slate explores the confusion over potential health benefits for these added bacteria.

The bacteria that live inside us seem to play an important role regulating metabolism, the immune system and the nervous system, but scientists have a lot to learn about how those interactions take place.

Researchers at Emory have been clarifying exactly how probiotic bacteria promote intestinal health. Andrew Neish and his colleagues have found that the bacteria give intestinal cells a little bit of oxidative stress, which is useful for promoting the healing of the intestinal lining.

Beneficial bacteria induce reactive oxygen species production by intestinal cells, which promotes wound healing.

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Emory University Hospital Set to Be Launch Site for EPIC

Can it really be possible to transform a person’s own cells into a weapon against various forms of disease? And what if those very cells could be retrained to attack cancer cells or to prevent autoimmune diseases?

Answers to these questions and many more are about to soon be realized, as Emory University Hospital will serve as the launch site for the very appropriately-named EPIC (Emory Personalized Immunotherapy Center).

The new Center, which is the creation of Dr. Jacques Galipeau, MD, professor of hematology and medical oncology & pediatrics of Emory University, will soon be operational after final touches have been put on construction of the lab. This cell processing facility will foster development of novel personalized cellular therapies for Emory patients facing catastrophic ailments and unmet medical needs.

According to Galipeau, the premise of EPIC and its overlying mission will focus on cellular and biological therapies that use a patient’s own cells as a weapon to seek and destroy cells that actually make a person sick. In partnership with the Winship Cancer Institute of Emory University, Children’s Healthcare of Atlanta, Aflac Cancer & Blood Disorders Center and the Emory School of Medicine, EPIC seeks to improve the health of children and adults afflicted with cancer and immune disease.

“First and foremost, we seek to bring a level of care and discovery that is first in Georgia, first in human and first in child. Blood and marrow derived cells have been used for more than a quarter century to treat life threatening hematological conditions and are now established therapies worldwide. More recently, the use of specific adult somatic cells from marrow, blood and other tissues are being studied in cellular medicine of a wide array of ailments including heart, lung, neurological and immune diseases,” says Galipeau. “The use of blood borne immune cells can also be exploited for treatment of cancer, autoimmune disease, organ transplantation and chronic viral illnesses such as HIV.”

Galipeau said that once operational, EPIC will begin by working with Crohn’s disease in pediatric and adult patients, an inflammatory bowel disease. Symptoms of Crohn’s disease include severe abdominal pain, diarrhea, fever, weight loss, and the inability for a child to properly grow. Resulting bouts of inflammation may also affect the entire digestive tract, including the mouth, esophagus and stomach.  In some cases, a radical surgery involving the removal of part of the lower intestinal tract is required.

“There is no current answer for what specifically causes Crohn’s disease, nor is there a cure. But we hope that through our research and efforts, we will be able to first target the inflammatory mechanisms in these patients through immunotherapy, and in turn reduce the amount of flare-ups and limit  the damage that occurs from this disease,” says Galipeau.

Galipeau says the EPIC program could represent a powerful cornerstone to the launch and the development of an entirely new, Emory-based initiative which bundles the strengths of the School of Medicine, Emory University Hospital, Children’s Healthcare of Atlanta, and many Woodruff Health Sciences Center centers of excellence,” says Galipeau.

“My ultimate goal is to elevate the biomedical scientific and scholarly enterprise to a higher level – making a difference in the lives of people. The EPIC program and multi-levels of support could be a fundamental underpinning to our success.”

Posted on by Lance Skelly in Immunology Leave a comment