Brain organoid model shows molecular signs of Alzheimer’s before birth

In a model of human fetal brain development, Emory researchers can see perturbations of epigenetic markers in cells derived from people with familial early-onset Alzheimer’s disease, which takes decades to appear. This suggests that in people who inherit mutations linked to early-onset Alzheimer’s, it would be possible to detect molecular changes in their brains before birth. The results were published in the journal Cell Reports. “The beauty of using organoids is that they allow us to Read more

The earliest spot for Alzheimer's blues

How the most common genetic risk factor in AD interacts with the earliest site of neurodegeneration Read more

Make ‘em fight: redirecting neutrophils in CF

Why do people with cystic fibrosis (CF) have such trouble with lung infections? The conventional view is that people with CF are at greater risk for lung infections because thick, sticky mucus builds up in their lungs, allowing bacteria to thrive. CF is caused by a mutation that affects the composition of the mucus. Rabindra Tirouvanziam, an immunologist at Emory, says a better question is: what type of cell is supposed to be fighting the Read more

influenza

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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GRA partnership promotes research collaboration, grows economy

“Other states wish they had what Georgia has: Research universities that work together, and a unified commitment from industry, government and academia to grow a technology-based economy,” states Michael Cassidy, president and CEO of the Georgia Research Alliance (GRA) in the GRA’s recent annual report.”

As one of six GRA universities, Emory has benefited from this unique partnership in numerous ways: through its 11 Eminent Scholars, multidisciplinary university and industry collaborations, and support for research in vaccines, nanomedicine, transplantation, neurosciences, pediatrics, biomedical engineering, clinical research, and drug discovery.

Emory is featured throughout the report, including

  • The Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory and its four eminent scholars, Xiaoping Hu, PhD, Eberhard Voit, PhD, Barbara Boyan, PhD and Don Giddens, PhD.
  • Emory transplant medicine expert and GRA Eminent Scholar Allan Kirk, MD, PhD, who collaborates with Andrew Mellor, PhD at the Medical College of Georgia on research to find enzymes that could keep the body from rejecting newly transplanted organs.
  • The Emory-University of Georgia Influenza Center of Excellence and its leading collaborators, GRA Eminent Scholar and Emory Vaccine Center Director Rafi Ahmed, PhD, and Emory microbiologist Richard Compans, PhD, along with UGA GRA Eminent Scholar Ralph Tripp.
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NIAID Director Fauci: link seasonal and pandemic flu preparedness

Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, delivered the keynote address Sunday, April 18, as part of a three-day conference on H1N1 Virus: The First Pandemic of the 21st Century, sponsored by the Emory-UGA Influenza Pathogenesis and Immunology Research Center.

One of the most important lessons from this past year’s pandemic, Fauci said, is the need to “connect the dots” between seasonal and pandemic influenza and not view them as two separate phenomena.

Fauci enthusiastically supports the CDC’s call for universal flu vaccination.

“Rather than trying to figure out one priority group over another,” Fauci said, “if we can get into a rhythm of getting most people vaccinated each year, we will have most of the population with some degree of immunity. We will get into a situation where we don’t need to go from a seasonal approach to a crisis approach.

Read more

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Predictive Health: Lessons learned from H1N1

Dr. Carlos del Rio possesses a keen view of how the novel H1N1 virus emerged last spring. Del Rio was in Mexico as the virus established itself south of the border. Its rapid, far-reaching spread marked the first influenza pandemic of the 21st century.

During Emory’s fifth annual predictive health symposium, “Human Health: Molecules to Mankind,” del Rio discussed his experiences in Mexico, what we’ve learned, and what novel H1N1 has to do with predictive health. View a video of his presentation and five lessons learned. 

Only a day after the virus was identified, on April 23, Mexican authorities closed schools, called off sporting events, and canceled religious gatherings. Known as “social distancing,” these actions led to a decrease in cases, an important lesson, says del Rio. The public knew what to do, they were cooperative, and what’s more, they applied a lot of peer pressure when it came to hand washing and sneezing hygiene.

Another lesson learned: preparation paid off. Anticipating a pandemic, The World Health Organization had earlier mandated that countries draw up influenza pandemic plans. “Those plans were incredibly helpful in getting people to work together, communicate, and know what to do,” says del Rio.  Interestingly, the plans in Mexico and the United States were aimed at a virus projected to originate from an avian source from southeastern Asia. “It was not developed for a swine virus coming from inside the country,” explained del Rio.

Novel H1N1, even though it’s thought of as a swine virus is in fact only about 47% swine–30% from North American swine and 17% from Eurasian swine. The virus also contains human and avian strains. That’s important, says del Rio, because the characteristics of its genes determine how symptoms, susceptibility, and immunity manifest themselves.

“What we’re seeing nowadays is the new strain has crowded out the seasonal influenza virus,” he says. Thus far, most of the deaths from novel H1N1 have been in children, young adults, and pregnant women. “The people who are dying are a very different group than in previous flu seasons,” says del Rio. 

Carlos del Rio, MD

Carlos del Rio, MD

Del Rio says a lot was learned early on about the novel virus thanks to frequent and transparent international communication. This flu pandemic is really the first to occur in this era of 24-hour newscasts and the Internet. So there’s a challenge for health workers: how do you continue to communicate in an effective way. “One thing you say one day may be contradicted the next day because you have new information. How do you make people understand that you weren’t lying to them before, but you have updated information and that information is continuously changing.”

In trying to predict what’s in store for the current flu pandemic, researchers are looking back at past pandemics. Last century, there were three major flu pandemics. The largest and most important was the 1918 pandemic.

“A couple of things that happened back then are very important: one was there was a second wave that was actually much more severe and much more lethal than the first one.” says del Rio. “And over the summer, the virus actually changed. It started very much like it did this time. It started in the spring and then we had a little blip, and then we had a big blip in the second wave, and then almost a third wave. So, clearly influenza happens in waves, and we’re seeing the same thing happening this time around.”

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Importance of flu vaccinations for pregnant women

Pregnant women are at the top of the Center for Disease Control and Prevention’s priority list when it comes to vaccinating people against the novel H1N1 flu virus this year. Not only should pregnant women receive the 2009 H1N1 vaccine, they should also receive the usual seasonal flu vaccine, say Emory experts.

Staying healthy in pregnancy

Staying healthy in pregnancy

Because pregnancy weakens the immune system, a pregnant woman who gets any type of flu has a greater chance for serious health problems. Pregnant women who contract H1N1 flu are more likely to be admitted to the hospital, compared with other people in general that get H1N1 flu. Pregnant women are also more likely to have serious illness, including pneumonia and death from this particular novel strain.

Both vaccines are made with a dead, or inactivated, flu virus and are given as an injection, usually in the arm. The other type of flu vaccine is a nasal spray and is not recommended for pregnant women. The nasal spray vaccine is safe for women after they have delivered, even if they are nursing.

A recent study by Emory researchers found that seasonal flu vaccination of pregnant women can benefit both mothers and infants, says Kevin Ault, MD, associate professor in the Department of Gynecology and Obstetrics at Emory.

Saad B. Omer, MBBS, MPH, PhD, assistant professor of global health at Emory’s Rollins School of Public Health, served as senior author on the report, published in the American Journal of Obstetrics & Gynecology. The study shows that there is substantial evidence that vaccination is not only safe for pregnant women but that it is critical for protecting women and their infants against serious complications from the flu.

Other members of the research team included Ault and Carlos del Rio, MD, professor and chair in the Hubert Department of Global Health, Rollins School of Public Health, Emory University.

The seasonal flu shot has been given to millions of pregnant women over several decades . Flu shots have not been shown to cause any harm to pregnant women or their babies. The 2009 H1N1 flu vaccine is being made in the same way and by the same manufacturers as the seasonal flu vaccine, explains Ault.

Ault also serves as principal investigator of a seasonal flu vaccine clinical trial underway at Emory Vaccine Center involving pregnant women.

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Students and faculty aid CDC for H1N1 response

Last spring, as H1N1 avian influenza spread across the globe, the Centers for Disease Control and Prevention put out a call asking students to assist. Within three days, 85 students from Emory’s Rollins School of Public Health (RSPH) had volunteered.

RSPH students Nick Schaad (left) and Michael Marrone

RSPH students Nick Schaad (left) and Michael Marrone

Nick Schaad was among the students authorized to help man the CDC’s Emergency Operations Center at the height of the novel H1N1 outbreak. Once the CDC began to identify influenza clusters, students began conducting phone surveys.

Schaad says he was involved in the St. Francis prep school survey in New York. Students and staff member who were sick with any flu-like symptoms were identified. The team called them and asked about the size of their household, what they might have done to protect themselves, and any recent travel. The goal was to learn as much possible about H1N1 in advance of the fall flu season.

Like the students they teach, RSPH faculty became engaged in the H1N1 epidemic. Last spring, Emory physician and microbiologist Keith Klugman, MD, PhD, was recruited to join the CDC’s Team B, which includes experts from outside the CDC to quickly review and inform the agency’s efforts. CDC created Team B in the early 2000s to cope with the growing complexity of public health emergencies.

Keith Klugman, MD, PhD

Keith Klugman, MD, PhD

Klugman says his role included the bacterial complications of influenza. Evidence from 1918, notes Klugman, clearly shows that the great majority of deaths were due to bacterial complications of the flu. In other words, the flu itself could occasionally cause death on itss own. But it caused death mostly by facilitating a synergistic lethality between itself and bacteria.

Although much has changed since 1918, the bacteria that caused so many deaths still exist but are susceptible to antibiotics.

Klugman notes the evolution of the flu. He says so far it’s generally been moderate. However, by mixing with the circulating flu in the Southern Hemisphere, it could mutate and become resistant to the first line of flu drugs. It could also become more severe. Says Klugman, “We must remain ever vigilant.”

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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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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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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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