From left: RSPH dean Jim Curran, First Lady Jeannette Kagame, HIV/AIDS researcher Susan Allen, Vice Provost Philip Wainwright
Most of the discussion, when Rwanda’s First Lady Jeannette Kagame recently visited Emory, was not about HIV vaccines, and rightly so. It was about how far Rwanda has come as a country since the 1994 genocide [videos of author Philip Gourevitch discussing Rwanda].
Still,Â while introducing the First Lady and thanking her for her support of HIV/AIDS research in Rwanda, Susan Allen mentioned a clinical trial for a HIV vaccine that began last year in Rwanda, Kenya and the United Kingdom and is now wrapping up the vaccination phase. Her colleague in Kigali, Etienne Karita, is one of the principal investigators.
The vaccine uses replicating Sendai virus, which causes respiratory tract illness in rodents but not in humans, as a vector to deliver the HIV gag gene. The trial combines this vaccine, administered intranasally, in various configurationsÂ with an adenovirus-based vaccine. This is the first time that Sendai virus is beingÂ used in a HIV vaccine.
As IAVI Report’s Regina McEnery explains,Â researchers hope the Sendai vector might recruit targeted immune responses to mucosal tissues and provide an edge to the immune system when it is subsequently challenged by HIV.
In a future post, we plan to provide an additional update on HIV vaccine research, focusing on GeoVax and (separate, for comparison) a planned large-scale followup to the landmark RV144 Thai trial.
This complex diagram, showing the gene segments that encode lamprey variable lymphocyte receptors, comes from a recent PNAS paper published by Emory’s Max Cooper and his colleagues along with collaborators from Germany led by Thomas Boehm. Lampreys have moleculesÂ that resemble our antibodies in function, but theyÂ look very different at the protein level. The study of lamprey immunityÂ provides hints to how the vertebrate immune system has evolved.
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.
While preparing to discuss Ebola virology with Emory infectious disease specialist Aneesh Mehta next week, we noticed two recent research papers on which he is a co-author. Both have to do with organ transplantation, since Mehta isÂ Assistant Director of Transplant Infectious Diseases.
Fecal microbiota transplantation for refractory Clostridium difficile colitis in solid organ transplant recipients
Fecal transplant is gaining ground as a remedy for C. difficile-driven diarrheal infections, which can appear in patients whose normal intestinal bacteria are wiped out by antibiotics. Fecal transplant has not been widely studied in organ transplant recipients, who must take drugs to keep their immune systems from rejecting the transplanted organ, because of concerns about infectious disease complications. This paper describes two patients, one a lung transplant recipient and one a kidney transplant recipient, who received fecal transplants to resolve their C. difficile diarrhea without complications. The lead authors are infectious disease specialists Rachel Friedman-Moraco and Colleen Kraft. Kraft has beenÂ a pioneer in this area of research.
Renal transplantation using belatacept without maintenance steroids or calcineurin inhibitors
Medical school dean Chris Larsen and Emory Transplant Center executive director Tom Pearson (both co-authors) were key members on the team that developedÂ belatacept, a FDA-approved drug since 2011. Belatacept was designed to get away fromÂ the cruel paradox where a kidney recipient, to prevent transplant rejection, has to take calcineurin inhibitor drugs that slowly poison the kidney and cardiovascular health. Belatacept inhibits the immune response by a different mechanism. Yet transplant specialists have generally been cautious in moving toward a regimen that relies on it.
As reportedÂ in this paper, Emory transplant doctors tookÂ off the training wheels, aimingÂ to get to the point where kidney transplant recipients are takingÂ a once-a-month infusion of belatacept only. With some patients, it was possible to reach that goal, but not all. In fact, as the authors describe, some patients chose not to try to wean themselves off the other drugs, and doctors advised against the attempt for a handful. This clinical trial was also notable because some transplant recipients received immune-educational cells from their organ donors in the form of bone marrow.
The lead author, former Emory Transplant Center scientific director Allan Kirk, moved to Duke this spring.
Does hormonal contraception increase the risk for a woman to acquire HIV from an infected partner?
This topic, with implications for public health in countries where HIV risk is high, has been contentious. Some previous studies had found the answer to be yes, for methods involving injectable progesterone such as Depo-Provera. This led the World Health Organization in 2012 to advise women using progesterone-only injections to use condoms to prevent HIV infection.
At the recent AIDS 2014 meeting in Australia, Emory epidemiologist Kristin Wall presented data from public health programs in Zambia. This is another study emerging from the Zambia-Emory HIV Research Project directed by Susan Allen.
Wall’s presentation is available here.
Studying 1393 heterosexual couples with a HIV-positive male partner over 17 years, Wall and her colleagues found no significant difference in incidence rate per 100 couple years between hormonal and non-hormonal forms of contraception. Read more
A lot of evidence has piled up suggesting that inflammation plays a big role in the progression of Parkinson’s.
Immune system genes are linked to disease risk. People who regularly take NSAIDs such as ibuprofen have lower risk.Â Microglia, the immune system’s ambassadors toÂ the brain,Â have been observedÂ in PD patients.
Malu Tansey and her postdoc CJ Barnum make a convincing case for an anti-inflammatory — specifically, anti-TNF– therapyÂ to Parkinson’s. They’ve been working with the Michael J. Fox Foundation for Parkinson’s Research to push this promising approach forward.Â Please check it out.
In Greek mythology, the chimera was a monstrous fire-breathing creature composed of the parts of three animals: a lion, a snake and a goat.
Adoptive cell transfer is advancing as a cancer immunotherapy technique. It involves removing some of a patientâ€™s immune cells, culturing them in the laboratory, and then infusing the cells back into the patient. The idea is to enhance the ability of the immune cells to attack the tumors far beyond what the immune system was able of doing on its own.
Two promising examples are the National Cancer Instituteâ€™s approach of treating advanced melanoma with IL-2-stimulated immune cells, and several investigatorsâ€™ approach of genetically engineering T cells to attack leukemias or lymphomas.
Jacques Galipeau and colleagues at Winship Cancer Institute have developed a chimeric molecule for stimulating immune cells, which appears to have unique powers beyond simply the sum of its two parts. The molecule is called GIFT4, a fusion of the immune signaling molecules GM-CSF (often used in cancer treatment) and IL-4.
What applies to meat, vegetables and fish may also apply to cells for use in cell therapy: frozen often isn’t quite as good.
Ian Copland and colleagues from Emory’s Personalized Immunotherapy Center have a paper this week in Stem Cells Reports discussing how freezing and thawing stem cells messes them up. Specifically, it disrupts their actin cytoskeletons and impairs their ability to find their niches in the body. Culturing the cells for 48 hours after thawing does seem to correct the problem, though.
The findings have some straightforward implications for researchers planning to testÂ cell therapies inÂ clinical applications. The authors conclude:
Until such time as a cryopreservation and thawing procedure can yield a viable and fully functional MSC product immediately after thawing, our data support the idea of using live MSCs rather than post-thaw cryo MSCs for clinical evaluation of MSCs as an immunosuppressive agent.
Notably, the Emory Personalized Immunotherapy Center has built a process designed around offering never-frozen autologous (that is, the patient’s own)Â mesenchymal stem cells, as therapies for autoimmune disordersÂ such as Crohn’s disease.
Pigs are natural hosts for influenza viruses that can infect humans, in particular the 2009 and, going way back, 1918 H1N1 flu strains. So to understand how influenza infections spread in the body, biochemists and virologists look at pigs.
Biochemistry chair Rick Cummings’ group has a paper in PNAS this week examining the carbohydrates or glycans on the surfaces of pig lung cells, using their “shotgun glycomics” library approach. MMG graduate student Lauren Byrd-Leotis is the first author.
“The results illustrate the repertoire of specific, endogenous N-glycans of pig lung glycoproteins for virus recognition and offer a new direction for studying endogenous glycan functions in viral pathogenesis,” the team reports.