Antibody production: an endurance sport

To understand recent research from immunologist Jerry Boss’s lab on antibody production, think about the distinction between sprinting and long-distance Read more

Less mucus, more neutrophils: alternative view of CF

A conventional view of cystic fibrosis (CF) and its effects on the lungs is that it’s all about mucus. Rabin Tirouvanziam has an alternative view, centered on Read more

flu

A distinguished flu vaccine researcher

Congratulations to Richard Compans, PhD, who delivered the Dean’s Distinguished Faculty Lecture on May 12, joining a select group of Emory researchers who have received this award. After Dean Chris Larsen presented the award, Compans also received a Catalyst award from the Georgia Research Alliance, presented by GRA President and CEO Mike Cassidy.compans115a-2

At Emory, Compans has led research on ways to improve influenza vaccination, such as vaccines based on non-infectious virus-like particles and microneedle patches for delivery (now being tested clinically). The 2009 H1N1 flu epidemic, as well as concern about pandemic avian flu, have meant that Compans’ work has received considerable attention in the last several years. In his talk, he also discussed his early work on the structure of influenza virus, the virus’s complex ecology, and the limitations of current flu vaccines.

Compans was recruited to Emory from UAB in 1992 and was chair of Emory’s microbiology and immunology department for more than a decade. He was also instrumental in recruiting Rafi Ahmed to establish and lead the Emory Vaccine Center. He is now co-principal investigator of the Emory-UGA Center of Excellence for Influenza Research and Surveillance.

Some recent papers that illustrate the extent of Compans’ influence: Read more

Posted on by Quinn Eastman in Immunology Leave a comment

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

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Key to universal flu vaccine: embrace the unfamiliar

Vaccine researchers have developed a strategy aimed at generating broadly cross-reactive antibodies against the influenza virus: embrace the unfamiliar.

In recent years, researchers interested in a “universal flu vaccine” identified a region of the viral hemagglutinin protein called the stem or stalk, which doesn’t mutate and change as much as other regions and could be the basis for a vaccine that is protective against a variety of flu strains.

In an Emory Vaccine Center study, human volunteers immunized against the avian flu virus H5N1 readily developed antibodies against the stem region of the viral hemagglutinin protein. In contrast, those immunized with standard seasonal trivalent vaccines did not, instead developing most of their antibodies against the more variable head region. H5N1, regarded as a potential pandemic strain, is not currently circulating in the United States and the volunteers had not been exposed to it before.

The results were published Monday, August 25 in PNAS.

The key to having volunteers’ bodies produce antibodies against the stem region seemed to be their immune systems’ unfamiliarity with the H5N1 type of virus, says lead author Ali Ellebedy, PhD, postdoctoral fellow in the laboratory of Rafi Ahmed, PhD, director of Emory Vaccine Center and a Georgia Research Alliance Eminent Scholar.

Note: for a counterpoint, check out this 2013 Science Translational Medicine paper on how vaccination that induces anti-stem antibodies contributes to enhanced respiratory disease in pigs.

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Posted on by Quinn Eastman in Immunology Leave a comment

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!

Posted on by Quinn Eastman in Immunology Leave a comment

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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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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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.

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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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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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