The blind is off: Moderna COVID-19 vaccine study update

Amidst the tumult in the nation’s capital, a quieter reckoning was taking place this week for the Moderna COVID-19 vaccine clinical trial. Lab Land has been hearing from Emory-affiliated study participants that they’re finding out whether they received active vaccine or placebo. For example, Emory and Grady physician Kimberly Manning, who had written about her participation in the Moderna study in a Lancet essay, posted on Twitter Tuesday. She discovered she had received placebo, and Read more

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Immunology

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.

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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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