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

AIDS Vaccine 2010 conference brings global research focus to Atlanta

This week’s AIDS Vaccine 2010 conference, Sept. 28-Oct. 1, is underway at Atlanta’s Omni Hotel. Under the auspices of the Global HIV Vaccine Enterprise, the international meeting is hosted by the Emory Center for AIDS Research (CFAR).

Over 1,100 scientists, advocates, funders, and policy makers are attending 500 sessions about scientific discoveries and future directions for developing an effective HIV/AIDS vaccine. This goal is considered critical in fighting the ongoing epidemic, which newly infects 50,000 people each week around the world.

Emory HIV/AIDS researchers are playing a significant role in the meeting. The four co-chairs are Eric Hunter, PhD, co-director of the Emory CFAR; James Curran, MD, MPH, dean of Emory’s Rollins School of Public Health and co-director of the CFAR; Carlos del Rio, MD, chair of the Hubert Department of Global Health and co-chair of the CFAR; and Harriet Robinson, PhD, formerly of Yerkes Primate Center and Emory Vaccine Center and now at GeoVax, Inc.

Hunter led the opening press conference and opening session on Tuesday afternoon.

A fellowship program hosted 21 journalists from media outlets around the world.

Alan Bernstein, executive director of the Global HIV Vaccine Enterprise, emphasized the need to build a bridge between basic science and clinical research. On Wednesday, Bernstein will talk about the Enterprise’s new strategic plan for an HIV vaccine.

Dazon Dixon Diallo, director of the African-American women’s organization Sisterlove, noted that the South has been particularly hard hit by the AIDS epidemic, with over half the HIV cases in the United States. The human rights dimensions of the disease are enormous, she said, and engagement with community partners is essential in fighting HIV. Researchers need to solve the problem with the help of people who know the most about it.

Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases of the NIH, said that even though the road to an HIV vaccine has been a rocky one over the past 23 years, the limited success reported last year with the RV144 trial was the first signal that it is possible for a vaccine to block HIV acquisition, a finding that has re-energized the vaccine community.

Future directions for HIV vaccine research, said Fauci, will include research that builds on insights from the success of RV144, multiple clinical trials conducted as scientific tools and not just all-or-nothing aims for vaccine licensing, more research into the early events of HIV infection that could provide targets for vaccines, and new structure-based vaccines using newly discovered neutralizing antibodies.

“I don’t think there is any question we are going to get there,” said Fauci. “The light at the end of the tunnel is the science we are now implementing.”

Press conferences are streamed live and available for playback at the conference website:

For more information on Emory’s role in the conference and Emory HIV/AIDS research, including video, see the website.

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Respiratory infection may lead to weaker immunological memory

How you vaccinate helps determine how you protect. This idea lies behind many researchers’ interest in mucosal vaccines. How a vaccine is administered (orally/nasally vs intramuscular, for example) could make a difference later, when the immune system faces the bad guys the vaccine is supposed to strengthen defenses against.

How does the route of immunization affect the quality of immunity later on? For example, is a nasal spray best when trying to prevent respiratory infections?

A recent paper from Emory Vaccine Center director Rafi Ahmed’s laboratory challenges this idea. The paper was published in the Journal of Immunology. Scott Mueller, now an Australian Research Council research fellow at the University of Melbourne, is first author.

Memory T cells are a key part of a response to a vaccine, because they stick around after an infection, enabling the immune system to fight an invading virus more quickly and strongly the second time around. In the paper, the Emory team compared memory T cells that form in mice after they are infected in the respiratory system by a flu virus or throughout their bodies by a virus that causes meningitis (lymphocytic choriomeningitis virus or LCMV).

The authors engineered a flu virus to carry a tiny bit of LCMV (an epitope, in immunological terms) so that they could compare apples to apples by measuring the same kind of T cells. They found that memory T cells generated after a flu infection are weaker, in that they proliferate and stimulate other immune cells less, than after a LCMV infection. This goes against the idea that after a respiratory infection, the immune system will be better able to face a challenge in the respiratory system.

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When your immune system calls the shots

Bali Pulendran, PhD

A tiny invader, perhaps a virus or a microbe, enters the body, and our ancient immune system responds. But how does it know what kind of invader has landed? And once it knows, how does it decide what kind of immune response it should launch?

In humans, the immune system consists of two parallel systems working with one another to fend off invaders. One is the innate immune system, the other the adaptive immune system.

Immunologist Bali Pulendran studies how those two systems work together to identify and respond to all kinds of intruders including pathogens, viruses and microbes.

It’s the innate immune system’s job to recognize the first signs of infection—that is, the moment a pathogen enters the body. “In a sense they act as smoke detectors if you will,” says Pulendran. “Little alarms.”

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2009 H1N1 flu strain could give clues to universal flu vaccine?

Last year, when the H1N1 flu epidemic was a major public health concern, a relatively low proportion of individuals getting sick were elderly, compared to previous flu epidemics. To explain this, scientists hypothesized that flu strains that circulated decades ago were similar enough to the novel swine-origin H1N1 strain to provide some immune protection.

A universal flu vaccine would eliminate the guesswork associated with the yearly flu shot

Now, researchers at Emory’s Influenza Pathogenesis & Immunology Research Center have directly tested that hypothesis in mice, and it holds up. Exposure of mice to flu strains that circulated in 1947 or 1934 induced “robust cross-protective immune responses” and can protect them against a lethal challenge with 2009 H1N1 virus, they report in Journal of Immunology.

Ioanna Skountzou and Dimitrios Koutsananos are co-first authors of the paper.

The Emory team, led by Joshy Jacob, also reports that antibodies produced in response to the 2009 H1N1 flu strain exhibit broad cross-reactivity — they react with other H1N1 strains as well as against H3N2 flu strains. They write:

The fact that the 2009 H1N1 virus can induce such cross-reactive Abs raises the intriguing possibility that viruses such as A/California/04/2009 can be used for vaccines to induce broadly cross-reactive humoral immune responses against influenza viruses. Identifying the mechanism behind this broad reactivity may enable us to design broadly cross-reactive universal influenza vaccines.

National Institute of Allergy and Infectious Diseases director Tony Fauci, when he was at Emory for the H1N1 flu conference in April, discussed the idea of a universal flu vaccine:

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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.

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Preparing for H1N1

James Steinberg, MD

James Steinberg, MD

With the novel H1N1 virus gaining a foothold in the northern hemisphere, anxious doctors, researchers and members of the public are carefully watching its movement and behavior.

Even before WHO declared novel H1N1 a pandemic late last spring, Emory University had been readying for its arrival. James Steinberg, MD, chief medical officer at Emory University Hospital Midtown, has been at the forefront of that preparation.

“A few years ago a decision was made to fund a center for emergency preparedness and response,” says Steinberg. “Having CEPAR, headed by Dr. Alex Isakov, gave us a leg up on preparing for this pandemic. Concern about the avian flu a few years ago sparked a pandemic plan and an antiviral plan. Having those plans on board helped us hit the gate running with the swine flu.”

To listen to Steinberg’s own words about novel H1N1 and its effect on the current flu season, access Emory’s new Sound Science podcast.

An expert in infectious disease, Steinberg says three key factors go into the making of a pandemic. “A virus can cause a pandemic when it can cause significant disease, when it’s a new virus to which people don’t have any immunity, and when the virus has the capacity to spread from person to person,” Steinberg says. “The novel H1N1 virus appears to meet all three of these characteristics.”

Steinberg cautions that the word pandemic has a horrible connotation. “We think of the 1918 pandemic that killed 50 to 100 million people worldwide, more people than were killed during World War I itself,” says Steinberg. “But there are pandemics in which the bumps in mortality have been modest.”

The H1N1 virus spreads from person to person via large droplets, the ones that fall quickly onto surfaces. These viruses can be spread by being close to an infected person who is coughing or sneezing or by touching contaminated surfaces. That’s why hand washing reduces the chance of infection.

Thus far, the novel strain of H1N1 has been relatively mild. Most of those infected have recovered without hospitalization or medical care, but according to the CDC some groups are at higher risk and should be vaccinated first. These include pregnant women, people who live with or care for children younger than 6 months of age, healthcare and emergency medical services personnel, persons between the ages of 6 months and 24 years, and people ages 25 through 64 who have chronic health conditions.

Initial supplies of the nasal mist H1N1 vaccine are expected to be available this week, followed soon by the injectable vaccine. The regular seasonal flu vaccine will not provide protection against the novel H1N1 strain, so people will need both vaccines.

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Jeff Koplan discusses H1N1 on panel

Experts on H1N1 influenza are collaborating all across the country to learn more about the virus and how to prevent its transmission. In a race against time, Emory studies are taking place in the lab and in human clinical trials to help find a vaccine that can be used in the near weeks to come.

Recently, Emory’s Jeff Koplan, MD, vice president for global health and past CDC director, participated in a Breakthroughs panel sponsored by Big Think, Pfizer and Discover to discuss the latest issues in pandemic and genomic science, fields that have not only made big headlines recently but also promise to be two of the most pressing topics in global science and medicine in coming years.

Jeffrey P. Koplan, MD, MPH

Jeffrey P. Koplan, MD, MPH

The panel focused on the real-time, round-the-clock scientific mission to understand the history, significance, and future of the new strain of flu that emerged suddenly this spring. Panelists included Koplan; Barry Bloom, Joan L. and Julius H. Jacobson Professor of Public Health at Harvard; Peter Palese, chairman of the microbiology department at Mt. Sinai Medical Center; and Michael Worobey, ecologist and evolutionary biologist at the University of Arizona.

View: Superbug – Are We Prepared for The Next Great Plague?


Emory began signing up several hundred interested volunteers several weeks ago for a clinical trial of the H1N1 vaccine along with the seasonal flu vaccine. About 170 adults have now been vaccinated in the trial, which will last about nine weeks and involve several vaccinations and blood tests. A clinical trial testing the H1N1 vaccine in children will begin at Emory and Children’s Healthcare of Atlanta in the next few days, followed by another adult clinical trial adding an adjuvant to the H1N1 vaccine.

In addition, a multi-pronged attack against the H1N1 virus by Emory researchers is using a new method of rapidly producing highly targeted monoclonal antibodies to develop a diagnostic test as well as a temporary therapy to stave off the H1N1 virus. The antibodies, which can be isolated from a small amount of the blood of humans infected with the virus, could be targeted against H1N1 and rapidly reproduced to detect or attack the virus.

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H1N1 flu clinical studies start at Emory today

Emory doctors discuss H1N1 studies

Emory doctors discuss H1N1 studies

Today Emory researchers began vaccinating volunteer participants in the first of several planned clinical trials of a new H1N1 vaccine. A morning press briefing attended by Atlanta and national media provided Emory a platform to inform the public.

The clinical trials are expected to gather critical information that will allow the National Institutes of Health to quickly evaluate the new vaccines to determine whether they are safe and effective in inducing protective immune responses. The results will help determine how to begin a fall 2009 pandemic flu vaccination program.

Emory began signing up several hundred interested volunteers about two weeks ago and has been screening the volunteers to make sure they fit certain criteria. Volunteers will receive their first vaccinations over the first week of the trial and will return several times over the course of nine weeks to receive additional vaccinations and blood tests.

H1N1 clinical trial volunteer

H1N1 clinical trial volunteer

The clinical trials are in a compressed timeframe because of the possible fall resurgence of pandemic H1N1 flu infections that may coincide with the circulation of seasonal flu strains.

The clinical trials are being conducted by the eight Vaccine and Treatment Evaluation Units (VTEUs), supported by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH).

For more information about the Emory flu clinical trials, call 877-424-HOPE (4673) for the adult and senior studies, or 404-727-4044 for the pediatric studies.

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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.

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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.

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