Virginia Commonwealth University School of Medicine researchers have made an important advancement toward developing a vaccine against the debilitating and potentially deadly tick-transmitted disease, human granulocytic anaplasmosis (HGA).
During the past several years, experts have seen a steady rise in the incidence of human infections caused by tick-transmitted bacterial pathogens — making the need for a vaccine critical. Successful vaccine development hinges on knowing what to target to prevent disease, and the VCU team has identified three such proteins on the surface of the HGA agent.
Jason A. Carlyon, Ph.D.
HGA is caused by a bacterium called Anaplasma phagocytophilum. HGA is transmitted by the same ticks that transmit Lyme disease, and it is the second most-common tick-borne disease in the United States. Between 2003 and 2012, the number of cases reported to the Centers for Disease Control and Prevention increased more than sixfold. However, evidence indicates that many more cases go undocumented. The disease is also found in Europe and Asia and can affect dogs, cats, horses and sheep.
In a study, published in the August issue of the journal Cellular Microbiology, researchers report the discovery of a protein called A. phagocytophilum invasion protein A, or AipA, found on the surface of the bacterium. It is a key player in mammalian cell invasion. They identified the specific region of this protein that is necessary for infection.
Further, they discovered that AipA works together with two other previously identified A. phagocytophilum surface proteins, OmpA and Asp14, to enable the pathogen to optimally invade host cells.
“This is an important finding because it highlights that pathogens use cooperative, even redundant mechanisms to invade host cells,” said lead investigator Jason A. Carlyon, Ph.D., associate professor and a George and Lavinia Blick Scholar in the Department of Microbiology and Immunologyin the VCU School of Medicine.
“Based on these findings, an effective preventative or therapeutic approach would be best achieved by targeting all three factors, rather than just one. Our research is a promising lead towards vaccine development against granulocytic anaplasmosisand is a blueprint for developing prophylactic and therapeutic approaches against pathogens that use multiple surface proteins to infect,” he said.
“Furthermore, we have determined that humans and animals make antibodies against AipA, OmpA, and Asp14 during granulocytic anaplasmosis, which means they could be used to develop effective diagnostic tests for the disease.”
Carlyon is working with Richard T. Marconi, Ph.D., professor of microbiology and immunology in the VCU School of Medicine, to translate these findings into a vaccine against granulocytic anaplasmosis. A patent application has been filed and the technology is available for licensure. For further information, contact VCU Innovation Gateway email@example.com.
This study builds on previously published work from the Carlyon lab. In 2012 and 2013, the team identified OmpA and Asp14, and determined that they worked together to promote A. phagocytophilum infection.
But, at that time, they also determined that a piece of the puzzle was missing.
“While using antibodies to target both did significantly reduce infection of host cells, the blocking was incomplete. This suggested to us the involvement of at least one additional Anaplasma protein, which, in this study, we identified as AipA,” Carlyon said.
Next, the team will identify the key regions necessary for infection for surface proteins, OmpA and Asp14, and then validate whether targeting the regions of all three proteins prevents infection using a mouse model. According to Carlyon, the information could be used to develop a “trifecta vaccine” to target the relevant regions of the three proteins, and thereby provide effective protection against infection.
The findings are highlighted as the Editor’s Choice in the August print issue of the journal Cellular Microbiology.
The study, titled “Anaplasma phagocytophilum surface protein AipA mediates invasion of mammalian host cells,” appeared online on April 3.
Read the study abstract here: http://onlinelibrary.wiley.
Carlyon collaborated with researchers from VCU, University of California at Davis and Yale University.
This work was supported by the National Institutes of Health grants R01 AI072683, R01 AI67830, and R01 AI141440; and the United States Department of Commerce Economic Development Administration. The VCU Flow Cytometry and Imaging Shared Resource Facility is supported in part by funding from NIH-NCI Cancer Center support grant 5P30 CA016059.
Virginia Commonwealth University is a major, urban public research university with national and international rankings in sponsored research. Located in downtown Richmond, VCU enrolls more than 31,000 students in 223 degree and certificate programs in the arts, sciences and humanities. Sixty-eight of the programs are unique in Virginia, many of them crossing the disciplines of VCU’s 13 schools and one college. MCV Hospitals and the health sciences schools of Virginia Commonwealth University comprise VCU Medical Center, one of the nation’s leading academic medical centers. For more, see www.vcu.edu.
Sathya Achia Abraham | Eurek Alert!
New study points the way to therapy for rare cancer that targets the young
22.11.2017 | Rockefeller University
Penn study identifies new malaria parasites in wild bonobos
21.11.2017 | University of Pennsylvania School of Medicine
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
22.11.2017 | Business and Finance
22.11.2017 | Physics and Astronomy
22.11.2017 | Physics and Astronomy