Researchers at Emory have been revealing several connections between cellsâ€™ responses to starvation and immunological memory. The latest example of this is a paper in Nature Immunology from Rafi Ahmedâ€™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
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 inÂ 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 toÂ enhanced respiratory disease in pigs.
Immunologists reported recently that the drug rapamycin, normally used to restrain the immune system after organ transplant, has the unexpected ability to broaden the activity of a flu vaccine.
The results, published in Nature Immunology, indicate that rapamycin steers immune cells away from producing antibodies that strongly target a particular flu strain, in favor of those that block a wide variety of strains. The results could help in the effort to develop a universal flu vaccine.
This study was inspired by a 2009 Nature study from Koichi Araki and Emory Vaccine Center director Rafi Ahmed, reports Jon Cohen in Science magazine. Read more
Gina Kolata has a section front story in Tuesday’s New York Times exploring the potential of a relatively new class of anticancer drugs. The drugs break through “shields” built by cancers to ward off the threat posed by the patient’s immune system. Many are based on blocking PD-1, an immune regulatory molecule whose importance in chronic infections was first defined by Emory’s Rafi Ahmed.
Of course, not every cancer research developmentÂ describedÂ as transformative inÂ the New York TimesÂ lives up to the hype. But the clinical trial results, reportedÂ in the New England Journal of Medicine, are solid enough that the researchers Kolata talks with think they are seeing “a moment in medical history when everything changed.”Â [Winship Cancer Institute’s John Kauh was a co-author on one of the 2012 NEJM papers.]
Let’s take a moment to examine some of the roots of this story.Â Rafi Ahmed didnâ€™t set out to study cancer. For the last two decades, he and his colleagues have been studying T cells, parts of the immune system that are critical for responding to infections. Read more
Emory Vaccine Center director Rafi Ahmed, is a co-author on a recent Science paper advocating a â€œHuman Vaccines Projectâ€. Wayne Koff, chief scientific officer of IAVI (International Aids Vaccine Initiative) is lead author and several other vaccine experts are co-authors.
The idea behind a â€œHuman Vaccine Projectâ€ is to combine efforts at developing vaccines for major (but very different) diseases such as influenza, dengue, HIV, hepatitis C, tuberculosis and malaria, with the rationale that what scientists working on those diseases have in common is the Ray Ban outlet challenge of working with the human immune system.
Technology has advanced to the point where whole genome-type approaches can be brought to bear on vaccine problems. The authors cite work by Bali Pulendranâ€™s laboratory on â€œsystems vaccinologyâ€ and their analysis of the yellow fever vaccine as an example.
One major puzzle confronting vaccine designers is to coax the immune system into producing broadly neutralizing antibodies against a rapidly mutating virus, whether it is Gafas Ray Ban outlet influenza or HIV. Our own Cynthia Derdeyn has been analyzing this problem through painstaking work following how the immune system pursues a twisting and turning HIV.
An interesting related tidbit:
There are hints that the reverse engineering of vaccines has taken a leap forward in the case of RSV (respiratory syncytial virus): Scientists at Scripps Research Institute have designed vaccine components by computer and have used them to provoke neutralizing antibodies in monkeys.
Also check out Mike Kingâ€™s feature in Emory Health on HIV vaccine research.
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.Â 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.Â 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!
Scientists at Emory and the University of Chicago have discovered that the 2009 H1N1 flu virus provides excellent antibody protection. This may be a milestone discovery in the search for a universal flu vaccine.
Researchers took blood samples from patients infected with the 2009 H1N1 strain and developed antibodies in cell culture. Some of the antibodies were broadly protective and could provide protection from the H1N1 viruses that circulated over the past 10 years in addition to the 1918 pandemic flu virus and even avian influenza or bird flu (H5N1).
The antibodies protected mice from a lethal viral dose, even 60 hours post-infection.
The research is published online in the Journal of Experimental Medicine.
Some of the antibodies stuck to the â€œstalkâ€ region, or hemagglutinin (H in H1N1) protein part of the virus. Because this part of the virus doesnâ€™t change as much as other regions, scientists have proposed to make it the basis for a vaccine that could provide broader protection. The antibodies could guide researchers in designing a vaccine that gives people long-lasting protection against a wide spectrum of flu viruses.
The paperâ€™s first author, Emory School of Medicineâ€™s Jens Wrammert, PhD, says â€œOur data shows that infection with the 2009 pandemic influenza strain could induce broadly protective antibodies that are very rarely seen after seasonal flu infections or flu shots. These findings show that these types of antibodies can be induced in humans, if the immune system has the right stimulation, and suggest that a pan-influenza vaccine might be feasible.”
Rafi Ahmed, PhD, director of the Emory Vaccine Center, and a Georgia Research Alliance Eminent Scholar, is co-senior author of the publication, along with Patrick Wilson at University of Chicago.
- See YouTube for video commentary by Dr. Ahmed
- For access to raw video for media purposes, contact Kathi Baker, email@example.com, 404-727-9371 Office, 404-686-5500 Pager (ID 14455), 404-227-1871 Mobile.
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 fellowÂ 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.
â€œOther 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 GRAâ€™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.
Posted on June 30, 2010
Riders gather at the Hope Clinic of the Emory Vaccine Center for the final leg of their ride.
More than 130 bicyclists rode 200 miles in two days to raise $188,660 for AIDS vaccine research at the Emory Vaccine Center. The AIDS Vaccine 200 on May 22-23, sponsored by Action Cycling Atlanta, was the eighth annual ride. The series now has raised more than $680,000 for AIDS vaccine research.
This year’s riders traveled from Emory to Eatonton, Georgia, and back to Emory along with a volunteer crew.
Because of generous sponsorships, Action Cycling donates 100 percent of funds raised by participants to AIDS vaccine research. These unrestricted funds fill gaps that cannot be met by grant dollars alone.
Posted on June 11, 2010