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Immunology

World AIDS Day reminds of research priorities

AIDS quilt panels_shadowsEmory University is hosting an 800-panel display of The AIDS Memorial Quilt in recognition of World AIDS Day. “Quilt on the Quad,” on the Emory quadrangle, is the largest collegiate display and the second largest in the world today. An opening ceremony featured a talk by Sandra Thurman, president and CEO of the International AIDS Trust, based at Emory’s Rollins School of Public Health. Members of the Emory community read the names of each individual memorialized by a quilt panel on the quad.

An estimated 60 million people have acquired HIV, and 25 million people have died from AIDS. Emory scientists and physicians have been leaders in research to develop effective drugs and vaccines against HIV and AIDS. The Emory Center for AIDS Research is an official National Institutes of Health CFAR site. More than 120 faculty throughout Emory are working on some aspect of HIV/AIDS prevention or treatment.

More than 94 percent of HIV patients in the U.S. on life saving antiviral therapy take a drug developed at Emory. And many of the scientists within the Emory Vaccine Center are focused on finding an effective vaccine against HIV. A vaccine developed at the Vaccine Center and Yerkes National Primate Research Center is being tested nationally in a phase II clinical trial.

The Hope Clinic of the Emory Vaccine Center is conducting several clinical trials of HIV vaccine candidates through the HIV Vaccine Trials Network (HVTN) sponsored by the NIH. The HVTN 505 vaccine trial, which is currently enrolling at the Hope Clinic and 13 other cities around the country, is a test-of-concept efficacy trial for an NIH vaccine (DNA + Adnovirus – gag/pol/nef/EnvABC).

Mark Mulligan, MD, executive director of Emory’s Hope Clinic, emphasizes that on World AIDS Day there would be no better way to honor those who have already died or are already infected than to produce a vaccine that will protect their families and friends.

“The recent analysis of the RV144 Thai trial surprisingly taught us that an envelope glycoprotein vaccine regimen can protect (albeit modestly, thus far)! This is an amazing result that has re-ignited the field, and is capturing the attention of the community. We must do all we can to leverage this result for success,” Mulligan says. “Albert Sabin said that no scientist can rest while a vaccine that might help humanity sits on the shelf. To me, this underscores the importance of successfully executing the HVTN 505 trial.”

Posted on by Holly Korschun in Immunology Leave a comment

Aging T cells think they’re something else

T cells start to lose their identities as they get older, recent Emory research indicates.

Immunologists Cornelia Weyand and Jorg Goronzy, who are codirectors of the Lowance Center for Human Immunology at Emory University School of Medicine, have a just-published paper in the journal Blood describing this phenomenon.

Jorg Goronzy, MD, PhD and Cornelia Weyand, MD, PhD

Jorg Goronzy, MD, PhD and Cornelia Weyand, MD, PhD

Weyand and Goronzy show that with age, T cells begin to turn on genes that are usually turned on only in “natural killer” cells. NK cells play a major role in rejecting tumors and killing cells infected by viruses. They are white blood cells like T cells but they have a different set of receptors on their surfaces controlling their activities.

Many of these receptors act to hold the NK cells back; so when they appear on the T cells, their activation is dampened too, thus contributing to the slowing down of the immune system in elderly people.

The authors report that NK cell genes get turned on because they lose the “methylation” on their DNA. Methylation is a pattern of tiny modifications on DNA, emphasizing what’s important (or forbidden) in a given cell, sort of like a highlighter’s yellow pen on top of text.

Apparently, in elderly people (aged 70-85), the methylation is more “spotty” than in younger people (aged 20-30). It seems that after the DNA is copied several times, the highlighting gets fuzzy and the T cells start to look like their cousins, natural killer cells.

Posted on by Quinn Eastman in Immunology Leave a comment

Why vaccine compliance matters

An outbreak of measles in the state of Washington last year sickened 19 children. Of those who fell ill, 18 had something in common—they were not vaccinated.

Saad Omer aims to increase vaccine compliance to prevent childhood diseases.

Saad Omer aims to increase vaccine compliance to prevent childhood diseases.

For Emory Rollins School of Public Health researcher Saad Omer, the Washington outbreak is a perfect example of the effect on an entire community when individuals are unimmunized. His research aims to shed light on ways to encourage increased vaccine compliance for adults and their children.

Omer says vaccine-preventable diseases such as measles, influenza, and pertussis often start among persons who forego vaccinations, spread rapidly within unvaccinated populations, and also spread to other subpopulations.

In a recent New England Journal of Medicine article, Omer and his colleagues reviewed evidence from several states showing that vaccine refusal due to nonmedical reasons puts children in communities with high rates of refusal at higher risk for infectious diseases such as measles and whooping cough.

Even children whose parents do not refuse vaccination are put at risk because “herd immunity” normally protects children who are too young to be vaccinated, who can’t be vaccinated for medical reasons, or whose immune systems do not respond sufficiently to vaccination.

Research findings indicate that everyone who lives in a community with a high proportion of unvaccinated individuals has an elevated risk of developing a vaccine-preventable disease.

Read more about Omer’s research on vaccine refusals in the fall 2009 issue of Public Health magazine.

Omer also discusses the importance of vaccinating against the H1N1 virus in an Oct. 16 article in The New York Times.

Posted on by adobbs in Immunology Leave a comment

Reality check for HIV vaccine design

HIV doesn’t have a brain and it doesn’t strategize.

But the way that the virus mutates and evades the immune system in the early part of an infection, you might think it did.

Emory Vaccine Center researcher Cynthia Derdeyn and her colleagues have a new paper in PLOS Pathogens that is a reality check for researchers designing possible HIV vaccines. The results come from a collaboration with the Rwanda Zambia HIV Research Group. (Although the patients in this paper are from Zambia only.)

Red and green depict the parts of the HIV envelope protein that mutated in two patients (185F and 205F) in response to pressure from their immune systems. The rest of the envelope protein is blue.

Red and green depict the parts of the HIV envelope protein that mutated in two patients (185F and 205F) in response to pressure from their immune systems.

Recently there has been some excitement over the discovery of robust neutralizing antibodies in patients.

The bottom line, according to Derdeyn’s team: even if a vaccine succeeds in stimulating antibodies that can neutralize HIV, the virus is still going to mutate furiously and may escape those antibodies. To resist HIV, someone’s immune system may need to have several types of antibodies ready to go, their results suggest.

A companion paper in the same issue of PLOS Pathogens from South African scientists has similarly bracing results.

Posted on by Quinn Eastman in Immunology Leave a comment

H1N1 pediatric flu vaccine clinical trials underway

Emory doctors discuss H1N1 flu vaccine testing

Emory doctors discuss H1N1 flu vaccine testing

Clinical trials are underway at Emory and Children’s Healthcare of Atlanta testing an investigational H1N1 flu vaccine along with the seasonal flu vaccine. Emory will enroll about 100 children, ages six months to 18 years, and up to 650 children nationally will participate in the study.

The study will look at the safety of and measure the body’s immune response to the H1N1 flu vaccine. In addition, it will help determine how and when the vaccine should be given with the seasonal flu vaccine to make it most effective.

Another important factor is learning if there are any potential problems by giving the vaccines together, such as whether one vaccine will undermine the protective power of the other.

The answer is important because experts are predicting that both strains of flu will circulate this fall and winter.

The clinical trial is part of the Vaccine and Treatment Evaluation Units (VTEUs), supported by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH). At Emory, this team is led by Mark Mulligan, MD, executive director of the Hope Clinic of the Emory Vaccine Center.

The Emory pediatric clinical trial is taking place at the Emory-Children’s Center. It is led by Emory VTEU co-directors Harry Keyserling, MD, professor of pediatric infectious diseases at Emory School of Medicine and Paul Spearman, MD, chief research officer for Children’s Healthcare of Atlanta and vice chair of research for Emory’s Department of Pediatrics, along with Allison Ross, MD, Emory assistant professor of pediatric infectious diseases.

Keyserling says that because children and young adults are considered among the most vulnerable populations for new and emerging strains of influenza, such as the current H1N1 pandemic, it is critically important that testing for a vaccine is quick and efficient.

The pediatric trial follows the launch of a VTEU-led adult clinical trial of the H1N1 and seasonal flu vaccines, which began at Emory’s Hope Clinic on Aug. 10 and will continue with followup visits for the next six weeks by a group of more than 170 volunteers.

Posted on by sgoodwin in Immunology 1 Comment

Lampreys’ alternative immune system

Lampreys are primitive creatures – basically, tubes with teeth. Their primitive nature makes them a fascinating entry-point for studying the evolution of the immune system.

At Emory, Max Cooper and his colleagues have been studying lampreys’ versions of white blood cells. In a recent Nature paper, they show that lampreys have two kinds of cells that look very much like B and T cells in mammals, birds and fish.

Non-immunologists may shrug at this revelation.  But consider: lampreys have a completely different set of tools for fighting infections. They have proteins in their blood that glob on to invaders, but they don’t look anything like the antibodies found in mammals, birds and fish.

Lampreys in a laboratory tank

Lampreys in a laboratory tank. Courtesy of Masa Hirano.

Similarly, lampreys have cells that look like T Ray Ban outlet cells, in terms of some of the genes that are turned on. However, they don’t have MHC genes, which are important in human transplant medicine because they determine how and when T cells get excited and reject transplanted organs.

Lampreys are thought to be an early offshoot on the evolutionary tree, before sharks and fish, and way before critters that crawl on land. This suggests that the categories (B or T) came first even though the characteristic features of the cells (antibodies/responding to MHC) are different.

“Lampreys have the same types of cells, but they just use different building blocks to put them together,” Cooper says.

Cooper, now a Georgia Research Alliance Eminent Scholar and a member of Emory’s pathology department, made pioneering studies defining the role the thymus plays in immune development at the University of Minnesota in the 1960s. The thymus is where T cells develop and where they get their name.

He says he is now collaborating with Thomas Boehm in Freiburg, Germany to better understand the evolution of the thymus. Again, lampreys don’t have a thymus, but they may have an area next to their gills where the T-like cells develop.

John Travis at Science has a more extensive discussion of this research.

In a Darwin-anniversary essay, Travis tells the story of how the evolution of the immune system was a centerpiece of the 2005 Kitzmiller v. Dover trial, when a Pennsylviania school district’s requirement to teach intelligent design was successfully challenged.

Link to Sound Science podcast with Cooper

Posted on by Quinn Eastman in Immunology Leave a comment

Many roads to memory T cells

When our bodies encounter a bacteria or a virus, the immune system sends some cells out to fight the invader and keeps others in reserve, in order to respond faster and stronger the next time around. Vaccination depends on this phenomenon, called immunological memory.

Several recent papers — from Emory and elsewhere – provide insight into this process, and highlight this area of research as especially active lately.

Researchers led by Rafi Ahmed and Chris Larsen at Emory found that rapamycin, a drug usually given to transplant patients to block rejection, actually stimulates the formation of memory T cells. Rapamycin appears to nudge immune cells when they have to make a decision whether to hunker down to become a memory cell.

The immunosuppressant drug rapamycin was discovered in soil from Easter Island

The immunosuppressant drug rapamycin was discovered in soil from Easter Island

Similarly, the anti-diabetes drug metformin, which affects fatty acid metabolism, can also stimulate the formation of memory T cells, according to research that was published in the same issue of Nature.

In addition, Wnt signaling, which plays critical roles in embryonic development and cancer, influences memory T cell formation as well, according to a July paper in Nature Medicine.

To summarize — pushing on several different “buttons” produces the same thing: more memory T cells. How are the wires behind the buttons connected? Work by Ahmed and others may eventually help enhance vaccine efficacy or fight cancer with the immune system.

Rapamycin, the focus of the Ahmed/Larsen paper, was also recently found to slow aging in mice. However, with previous anti-aging research findings, translating results into the human realm has been a considerable challenge.

Posted on by Quinn Eastman in Immunology Leave a comment
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