Two items relevant to long COVID

One of the tricky issues in studying in long COVID is: how widely do researchers cast their net? Initial reports acknowledged that people who were hospitalized and in intensive care may take a while to get back on their feet. But the number of people who had SARS-CoV-2 infections and were NOT hospitalized, yet experienced lingering symptoms, may be greater. A recent report from the United Kingdom, published in PLOS Medicine, studied more than Read more

All your environmental chemicals belong in the exposome

Emory team wanted to develop a standard low-volume approach that would avoid multiple processing steps, which can lead to loss of material, variable recovery, and the potential for Read more

Signature of success for an HIV vaccine?

Efforts to produce a vaccine against HIV/AIDS have been sustained for more than a decade by a single, modest success: the RV144 clinical trial in Thailand, whose results were reported in 2009. Now Emory, Harvard and Case Western Reserve scientists have identified a gene activity signature that may explain why the vaccine regimen in the RV144 study was protective in some individuals, while other HIV vaccine studies were not successful. The researchers think that this signature, Read more

vaccines

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

Posted on 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 by Quinn Eastman in Immunology Leave a comment

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.

Posted on by Quinn Eastman in Immunology, Neuro Leave a comment

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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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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Cervical Cancer – Can Be Hard to Detect

MedicalHorizon

The Pap smear – also called Pap test – is part of the standard annual wellness exam for women’s health and used as a first step in detecting cervical cancer.  But according to a recent article published in the International Journal of Cancer,  the Pap test may not provide reliable results for certain types of cancer that are harder to detect.

Kevin Ault, MD, associate professor of obstetrics and gynecology at Emory University School of Medicine and investigator at the Emory Vaccine Center conducted a post-hoc analysis of the FUTURE I and FUTURE II (Gardasil) vaccine trials.  Based on that analysis Ault, a leading expert and pioneer in the field of human papilloma virus (HPV), says a regular Pap test is not always effective in diagnosing adenocarcinoma, because it starts high up in the cervical canal and may not be sampled by the Pap smear.

“There are a number of reasons the Pap smear could lead to inaccurate results. For example, the pathologist examining the cells could make an error, the gynecologist may not sample the cervix adequately or an infection could obscure the results,” says Ault.

According to Ault, andenocarcinoma is the second most common type of cervical cancer, accounting for about 20 percent of all cervical cancer cases. While the overall incident of cervical cancer is on the decline, Ault reports the proportion of cervical cancers that are andenocarcinoma is rising.

Cervical cancer is the eighth most common type of cancer in American women. More than 12,000 new cases of invasive cervical cancer are diagnosed each year, and more than 4,200 women in the U.S. die from of this disease annually* according to the American Cancer Society.  Scientists believe that pre-invasive cervical cancer may develop over a period of months or years after the cervix is infected with the sexually transmitted HPV.

“The take-away from this recent paper is the HPV test would be a better test for the harder to detect adenocarcinoma cervical cancer, if not all cervical cancer,” says Ault.

* 2010 data

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Reassuring news on viral immunity + HIV vaccine

A recent paper in Journal of Immunology suggests that a platform for an HIV vaccine developed by Yerkes National Primate Research Center scientists won’t run into the same problems as another HIV vaccine. Postdoc Sunil Kannanganat is the first author of the JI paper, with Emory Vaccine Center researcher Rama Amara as senior author.

Harriet Robinson, MD and Rama Rao Amara, PhD

Many HIV vaccines have been built by putting genes from HIV into the backbone of another virus. Some have used a modified cold virus (adenovirus 5). The vaccine developed at Yerkes uses modified vaccinia Ankara (MVA), a relative of smallpox and chicken pox.

Read more

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Re-energizing AIDS vaccine research

Emory President James Wagner welcomed participants Wednesday to the AIDS Vaccine 2010 conference in Atlanta, hosted by the Global HIV Vaccine Enterprise and locally hosted by the Emory Center for AIDS Research.

“Only occasionally are there scientific challenges that unite people powerfully towards a common goal,” Wagner said. “We are proud for the role we’ve been able to play in the pursuit of vaccine research. I am particularly pleased that so many students and young investigators have been able to participate in this conference.”

John Mascola from the Vaccine Research Center at the NIH gave the day’s first scientific talk, describing the discovery of broadly cross-reactive neutralizing antibodies to HIV and the ability to isolate those antibodies. This is the kind of recent discoveries that has re-energized the HIV vaccine research community.

Bette Korber of the Los Alamos National Laboratory noted that HIV mutations that escape immune response in some infected people are frequently susceptible in others. New “mosaic vaccines” can expand the breadth and depth of these immune responses, she said. She also described the effort underway in her laboratory to re-examine results of an earlier vaccine trial, VAX004, in light of new analytic strategies.

Giuseppe Pantaleo of the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland expressed the need to implement adaptive clinical trial study design. This theme — the need to examine clinical trial results early and often, and then adapt, rather than waiting for all results at the very end of a years-long trial — has been echoed often at the conference.

At a midday press briefing, Peter Kwong of the NIH Vaccine Research Center discussed his research with broadly neutralizing antibodies, one of which attacks the initial site of vital attachment to CD4 T cells.

Hendrik Streek from Harvard’s Ragon Institute described how vaccines induce antibody and CD4 response and contraction. Even though CD4 cells are the ones attacked during HIV infection, Streek believes CD4 responses may be a missing link to effective vaccine development

Alan Bernstein, executive director of the Global HIV Vaccine Enterprise, led a discussion of the new Enterprise Scientific Strategic Plan. Less than two out of five people who need treatment for HIV are receiving it, said Bernstein, which underscores the importance of an effective vaccine.

The new plan arrives at a time of great momentum and excitement in the field. A year of important advances has included discoveries about broadly neutralizing antibodies, new technologies, and a vaccine that demonstrated an immune response. The plan emphasizes novel clinical trials design, a strong commitment and engagement by many partners, and expanded diversity of funding by many stakeholders.

Jose Esparza, senior advisor on HIV vaccines to the Bill & Melinda Gates Foundation, emphasized the need to rapidly capitalize on new science, and said HIV vaccines are one of the foundation’s top priorities. High risk, high reward projects will be funded through the Gates Grand Challenges Explorations grants.

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