Before the cardiologist goes nuclear w/ stress #AHA17

Measuring troponin in CAD patients before embarking on stress testing may provide Read more

Virus hunting season open

Previously unknown viruses, identified by Winship + UCSF scientists, come from a patient with a melanoma that had metastasized to the Read more

#AHA17 highlight: cardiac pacemaker cells

Highlighting new research on engineering induced pacemaker cells from Hee Cheol Cho's Read more

vaccines

Threading the RSV needle: live attenuated vaccine effective in animals

Crafting a vaccine against RSV (respiratory syncytial virus) has been a minefield for 50 years, but scientists believe they have found the right balance.

A 3-D rendering of a live-attenuated respiratory syncytial virus (RSV) particle, captured in a near-to-native state by cryo-electron tomography. Surface glycoproteins (yellow) are anchored on the viral membrane (cyan), with ribonucleoprotein complexes inside (red). Image courtesy of Zunlong Ke and Elizabeth Wright.

Researchers at Emory University School of Medicine and Children’s Healthcare of Atlanta have engineered a version of RSV that is highly attenuated – weakened in its ability to cause disease – yet potent in its ability to induce protective antibodies.

The researchers examined the engineered virus using cryo-electron microscopy and cryo-electron tomography techniques, and showed that it is structurally very similar to wild type virus. When used as a vaccine, it can protect mice and cotton rats from RSV infection.

The results were published this morning in Nature Communications.

“Our paper shows that it’s possible to attenuate RSV without losing any immunogenicity,” says senior author Martin Moore, PhD, associate professor of pediatrics at Emory University School of Medicine and a Children’s Healthcare of Atlanta Research Scholar. “This is a promising live-attenuated vaccine candidate that merits further investigation clinically.”

The next steps for this vaccine are to produce a clinical grade lot and conduct a phase 1 study of safety and immunogenicity in infants, Moore says. Read more

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SIV remission follow-up

The surprising finding that an antibody treatment can push SIV-infected monkeys into prolonged remission, even after antiviral drugs are stopped, continues to rumble across the internet.

siv-a4b7-teaser-copy

Blue circles show how viral levels stayed low even after antiretroviral drugs were stopped.

The Science paper was featured on NIH director Francis Collins’ blog this week. NIAID director Anthony Fauci has been giving presentations on the research, which emerged from a collaboration from his lab and Tab Ansari’s at Emory. Fauci’s talk at the recent HIV prevention meeting in Chicago is viewable here.

At Lab Land, we were pleased to see that the watchdogs at Treatment Action Group had this to say:

“Media coverage of the paper has generally been accurate, but has had to wrestle with the uncertainty that exists among scientists regarding how ART-free control of viral load should be described.”

HIV pioneer Robert Gallo noted in an article accompanying the Science paper that the anti-integrin antibody treatment represents an emerging alternative to the vaunted “shock and kill” strategy, which he termed “soothe and snooze.” Note to reporters: the upcoming “Strategies for an HIV cure” conference at NIH in mid-November might be a good chance to compare the different strategies and put them in perspective.

Read more

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Malaria vaccine development: chimeric protein, no myth

Third in a series on malaria immunology from graduate student Taryn McLaughlin. Sorry for the delay last week, caused by technical blog glitches.

It’s easy for me to find reasons to brag when it comes to research here at Emory. However, even an unbiased person should be excited about the malaria vaccine platform being developed by Alberto Moreno at the Emory Vaccine Center.

His vaccine is based on a chimeric protein (a protein that is a combination of bits and pieces of multiple proteins, a la the creature from Greek mythology) that should get your immune system to target multiple stages of the Plasmodium vivax life cycle. Part of it targets the infectious sporozoite, part of it targets the blood stage merozoite, and part of it will even target the transmitted gamete in future versions. This seems like a no brainer. Of course we should be targeting multiple stages! 
Read more

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Why the RTS,S malaria vaccine is such a tease

Continuing from Monday’s post, IMP graduate student Taryn McLaughlin explains why the most advanced malaria vaccine is actually not that great.

Malaria has plagued humans for thousands of years. And while we have known the causative agents of the disease- for 150 years, malaria remains scientifically frustrating. In fact, one of the most common treatments for the disease is simply a derivative of a treatment used in ancient China.

One of the most frustrating features is that there is no sterilizing immunity. In other words, for many diseases once you are infected with the microbe responsible, you develop an immune response and then never get the disease again. Not so with malaria. Compounded with terrible treatment and the impracticality of ridding the world of mosquitos, a vaccine sounds like pretty much our only hope. And yet this has been scientifically challenging and unsuccessful for many many reasons.

In fact a number of vaccine candidates have come along in the last few decades that have seemed SO promising only to go on and break our hearts in clinical trials. The most recent of which is a vaccine that goes by the name RTS,S (named for the different components of the vaccine).

As a quick refresher, Plasmodium enters the body via mosquitos as a sporozoite. It then migrates through the skin going into the blood and eventually making it’s way to the liver. Here it goes inside liver cells where it replicates and turns into merozoites (such that one sporozoite becomes thousands of merozoites). This stage of the disease is asymptomatic. Some time later, all those merozoites burst out of your liver cells causing mayhem and invading your red blood cells. Here, they once again replicate and metamorphose. Fun times. Anyways, during the last stage, some of those plasmodium become gametes which get eaten by mosquitos thus completing the life cycle. Read more

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Why malaria vaccine development is hard

In recognition of World Malaria Day, Lab Land will have a series of posts from Taryn McLaughlin, a graduate student in Emory’s IMP program. Her posts will set the stage for upcoming news about malaria research at Emory and Yerkes. Taryn is part of Cheryl Day’s lab and is also an associate producer with the AudiSci podcast.

Those of us in the US are fortunate to not have to consider malaria in our day-to-day lives. Globally though, malaria is a serious public health threat with nearly 3.2 billion people at risk and close to half a million deaths every year. The scientific community has been developing malaria vaccines for decades. Yet a robust vaccine still remains elusive. Why?

IMP graduate student Taryn McLaughlin

IMP graduate student Taryn McLaughlin

One set of barriers comes from economics: malaria’s strongest impact is in developing countries. But there is just as strong a case to be made for scientific obstacles. Frankly, the parasite (technically a bunch of species of microbes that I’ll just lump together under the umbrella term Plasmodium) that causes malaria is just smarter than we are.

I’m only kidding, but it is a fascinating organism. Its complexity makes it difficult to pin down and also interesting to write about. But before we talk about why Plasmodium is such a pain, let’s first discuss what exactly makes an effective vaccine. Read more

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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.

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Connections between starvation and immunological memory

Researchers at Emory have been revealing several connections between cells’ responses to starvation and immunological memory. The latest example of this is a paper in Nature Immunology from Rafi Ahmed’s lab, showing that the cellular process of autophagy (literally: self-consumption) is essential for forming and maintaining memory T cells.

This finding has some practical implications for vaccination and could point the way to additives that could boost vaccine effectiveness in elderly humans. Researchers at Oxford have demonstrated that autophagy is diminished in T cells from aged mice, and T cell responses could be boosted in older mice using the autophagy-inducing compound spermidine. Read more

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Paul Offit: rock star of vaccine advocacy

This piece in the Los Angeles Times gives a helpful preview of what Paul Offit’s talk at Emory next week may be like. He also gave a keynote speech at the Association for Health Care Journalists meeting this spring.

Offit is the chief of the Division of Infectious Diseases and the Director of the Vaccine Education Center at the Children’s Hospital of Philadelphia. He is speaking at noon at the Health Sciences Research Building Auditorium on Nov. 18.

Offit is also speaking that morning at Childrens’ Scottish Rite hospital on the 1991 measles outbreak in Philadelphia. The emails I’ve been getting for the noon event ask people to register.

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Two heavy hitters in this week’s Nature

Two feature articles in Nature this week on work by Emory scientists.

One is from Virginia Hughes (Phenomena/SFARI/MATTER), delving into Kerry Ressler’s and Brian Dias’ surprising discovery in mice that sensitivity to a smell can be inherited, apparently epigenetically. Coincidentally, Ressler will be giving next week’s Dean’s Distinguished Faculty lecture (March 12, 5:30 pm at the School of Medicine).

Another is from Seattle global health writer Tom Paulson, on immunologist Bali Pulendran and using systems biology to unlock new insights into vaccine design.

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All about Saccharomyces boulardii

Pediatric infectious disease specialist Tracey Lamb earned recognition this week for her NIH New Innovator award. The goal of Lamb’s project is to develop a probiotic yeast as a platform for inexpensive oral vaccines.

“We have a long way to go to develop this vaccine Magliette Calcio A Poco Prezzo delivery system to the point where it is ready for testing in the clinic,” she says. “Now my lab can undertake more intensive research on this project to demonstrate that our design is effective in protecting against infection.”

Three points:

1. The probiotic yeast Lamb is planning to develop as a vaccine platform is Saccharomyces boulardii, which has been tested in clinical trials as a treatment for gastrointestinal disorders such as Clostridium dificile infection and several forms of diarrhea. It was originally isolated in the 1920s from fruit in Southeast Asia.

2. Saccharomyces boulardii is very close to standard baker’s yeast, Saccharomyces cerevisiae, and is actually considered a subspecies of S. cerevisiae. Genomic differences that http://www.magliettedacalcioit.com contribute to its probiotic properties are under investigation.

3. The New Innovator program, running since 2007, is one of the ways the National Institutes of Health seeks to reward especially creative or potentially transformative research proposals. The New Innovator awards, up to $1.5 million over five years, are meant for newly independent researchers building their careers. Lamb managed to snag Emory’s first.

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