Warren symposium follows legacy of geneticist giant

If we want to understand how the brain creates memories, and how genetic disorders distort the brain’s machinery, then the fragile X gene is an ideal place to start. That’s why the Stephen T. Warren Memorial Symposium, taking place November 28-29 at Emory, will be a significant event for those interested in neuroscience and genetics. Stephen T. Warren, 1953-2021 Warren, the founding chair of Emory’s Department of Human Genetics, led an international team that discovered Read more

Mutations in V-ATPase proton pump implicated in epilepsy syndrome

Why and how disrupting V-ATPase function leads to epilepsy, researchers are just starting to figure Read more

Tracing the start of COVID-19 in GA

At a time when COVID-19 appears to be receding in much of Georgia, it’s worth revisiting the start of the pandemic in early 2020. Emory virologist Anne Piantadosi and colleagues have a paper in Viral Evolution on the earliest SARS-CoV-2 genetic sequences detected in Georgia. Analyzing relationships between those virus sequences and samples from other states and countries can give us an idea about where the first COVID-19 infections in Georgia came from. We can draw Read more
•••

antibodies

Progress on universal flu vaccine

Flu viruses are constantly mutating and every year the seasonal flu shot is updated to keep up with the viruses that are making people sick. Readers interested in the prospect of a “universal flu vaccine” may have noticed some experimental progress on that theme this week.

The reports build on findings some years ago from Emory Vaccine Center researchers led by Rafi Ahmed. Ahmed’s team had showed that people infected by the 2009 H1N1 flu strain developed broadly protective antibodies, and separately, so did volunteers immunized against the H5N1 avian flu virus.

Some background: the head region of the flu virus’s mushroom-like hemagglutinin protein is more variable, and more exposed to the immune system, while the stem/stalk region is less variable.

The underlying idea is: if someone’s immune system is exposed to flu viruses different enough than what it has seen before (like in the 2009 H1N1 outbreak and the H5N1 study), the antibodies to the stem region become more important and more prominent.

The NIAID team fused the flu hemagglutinin to ferritin to make nanoparticles

The NIAID team fused the flu hemagglutinin to ferritin, a platform for further protein engineering.

This week, what the researchers from NIAID (Nature Medicine) and Scripps/J&J (Science) showed is that experimental vaccines made from the stem region only can be broadly protective in several animal models. This required some protein engineering and reconstruction because chopping off the head of the hemagglutinin protein makes it fall apart.

Emory Vaccine Center’s Walter Orenstein, in comments for Genetic Experts News Service, wrote:

These are animal studies, so we are some way off for development and testing of a vaccine in humans. The technique is promising and a step in the right direction. Read more

Posted on August 28, 2015 by Quinn Eastman in Immunology Leave a comment

Subset of plasma cells display immune ‘historical record’

You may have read about recent research, published in Science, describing a technique for revealing which viruses have infected someone by scanning antiviral antibodies in the blood.

Emory immunologists have identified corresponding cells in which long-lived antibody production resides. A subset of plasma cells keep a catalog of how an adult’s immune system responded to infections decades ago, in childhood encounters with measles or mumps viruses.

The results, published Tuesday, July 14 in Immunity, could provide vaccine designers with a goalpost when aiming for long-lasting antibody production.

“If you’re developing a vaccine, you want to fill up this compartment with cells that respond to your target antigen,” says co-senior author F. Eun-Hyung Lee, MD, assistant professor of medicine at Emory University School of Medicine and director of Emory Healthcare’s Asthma, Allergy and Immunology program.

The findings could advance investigation of autoimmune diseases such as lupus erythematosus or rheumatoid arthritis, by better defining the cells that produce auto-reactive antibodies.

Lee says that her team’s research on plasma cells in humans provided insights unavailable from mice, since mice don’t live as long and their plasma cells also have a different pattern of protein markers. More here.

Posted on July 15, 2015 by Quinn Eastman in Immunology Leave a comment

Carbohydrates not silent to immune system

Donor antibodies, administered intravenously or subcutaneously, make up a commercial product used to treat both immunodeficiencies and inflammatory or auto-immune diseases.

These preparations contain a complex mix of antibodies against glycans, the carbohydrate molecules on the outsides of cells, a Jan. 7 paper in Science Translational Medicine reveals.

At first glance, the findings are remarkable because:

A. Immunologists have long thought that carbohydrates, by themselves, are not good at provoking the immune system. (The assumption was: you need some protein for antigen presentation and getting T cells interested.) The data shows exceptions to the rule.

B. Some of the antibodies react against human carbohydrate structures. Instead of attacking them in an auto-immune fashion, they may actually be blocking viruses or bacteria from using those structures as gateways to infection.

The lab of Stephan von Gunten at the University of Bern collaborated with the National Center for Functional Glycomics led by biochemists Rick Cummings and David Smith at Emory to analyze the spectrum of carbohydrate structures bound by donor antibodies. Read more

Posted on January 12, 2015 by Quinn Eastman in Immunology Leave a comment

Max Cooper celebrated in Nature for 50 yrs of B cells

Emory’s Max Cooper was celebrated this week in Nature for his discovery of B cells in the 1960s, while working with Robert Good at the University of Minnesota.

Cooper in Good’s laboratory in the 1960s (source: National Library of Medicine)

B cells are immune cells that display antibodies on their surfaces, and can become antibody-secreting plasma cells. Without B cells: no antibodies to protect us against bacteria and viruses. Where B cells come from, and how they can develop such a broad repertoire of antibody tools, was a major puzzle of 20th century immunology, which Cooper contributed to solving. (See the Nature piece to learn why the “B” comes from the name of an organ in chickens.)

The authors did not mention that Cooper is now at Emory studying lampreys’ immune systems, which are curiously different from those of mammals. The similarities and differences provide insights into the evolution of our immune systems. In addition, scientists here are exploring whether lamprey’s antibody-like molecules might be turned into anticancer drugs.

Posted on January 8, 2015 by Quinn Eastman in Immunology Leave a comment

Alternative antibody architecture

This complex diagram, showing the gene segments that encode lamprey variable lymphocyte receptors, comes from a recent PNAS paper published by Emory’s Max Cooper and his colleagues along with collaborators from Germany led by Thomas Boehm. Lampreys have molecules that resemble our antibodies in function, but they look very different at the protein level. The study of lamprey immunity provides hints to how the vertebrate immune system has evolved.
PNAS-2014-Das-1415580111_Page_4

Posted on September 19, 2014 by Quinn Eastman in Immunology Leave a comment

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 June 20, 2013 by Quinn Eastman in Immunology Leave a 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 April 23, 2012 by Quinn Eastman in Immunology 1 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 September 22, 2009 by Quinn Eastman in Immunology Leave a comment

A new and faster way to diagnose and fight flu

flu imageA new method of rapidly producing highly targeted monoclonal antibodies could soon be used to rapidly diagnose H1N1 influenza. Just a month after vaccinating people with a seasonal flu vaccine, the researchers were able to use just a few tablespoons of the vaccinated individuals’ blood to generate antibodies against that specific strain of flu. The research was published last spring in Nature.

The scientists believe their discovery could be applied to any infectious disease. By using a few drops of blood from infected people, they could isolate antibodies to rapidly diagnose a newly emerging flu strain such as H1N1.

There are many variations of H1N1, says Rafi Ahmed, director of the Emory Vaccine Center and a Georgia Research Alliance Eminent Scholar, but this technology could be used to identify a very specific strain, such as the one we’re dealing with in the current pandemic. The diagnostic tests available now are not specific to any particular H1N1 strain.

Ahmed and his colleagues, including postdoctoral fellow Jens Wrammert, and Patrick Wilson from the University of Chicago, hope their work will lead to a new, specific test for H1N1 within the next several months.

Conventional methods of making human monoclonal antibodies are time-consuming and laborious, says Ahmed. For example, one method involves sifting through human B cells —white blood cells that make human antibodies—and then looking for specific cells that make the right antibodies.

Not only is the new method quicker and less cumbersome, it could be applied to almost any infectious disease. In any kind of emerging infection, speed is essential, says Ahmed.

To listen to Ahmed describe the new monoclonal antibody method, listen to Emory’s Sound Science podcast.

Posted on July 30, 2009 by admin in Uncategorized Leave a comment
« Previous   1 2