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!
Laboratory study: Scientists from Cologne explore a new approach to prevent newborn epilepsies
24.11.2015 | Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE)
U of T research sheds new light on mysterious fungus that has major health consequences
23.11.2015 | University of Toronto
Nerve cells cover their high energy demand with glucose and lactate. Scientists of the University of Zurich now provide new support for this. They show for the first time in the intact mouse brain evidence for an exchange of lactate between different brain cells. With this study they were able to confirm a 20-year old hypothesis.
In comparison to other organs, the human brain has the highest energy requirements. The supply of energy for nerve cells and the particular role of lactic acid...
In laser material processing, the simulation of processes has made great strides over the past few years. Today, the software can predict relatively well what will happen on the workpiece. Unfortunately, it is also highly complex and requires a lot of computing time. Thanks to clever simplification, experts from Fraunhofer ILT are now able to offer the first-ever simulation software that calculates processes in real time and also runs on tablet computers and smartphones. The fast software enables users to do without expensive experiments and to find optimum process parameters even more effectively.
Before now, the reliable simulation of laser processes was a job for experts. Armed with sophisticated software packages and after many hours on computer...
Researchers at Heidelberg University have devised a new way to study the phenomenon of magnetism. Using ultracold atoms at near absolute zero, they prepared a...
AWI researchers’ unique 15-year observation series reveals how sensitive marine ecosystems in polar regions are to change
The warming of arctic waters in the wake of climate change is likely to produce radical changes in the marine habitats of the High North. This is indicated by...
Berkeley Lab researchers develop nanoparticles that can carry therapeutics across the brain blood barrier
Glioblastoma multiforme, a cancer of the brain also known as "octopus tumors" because of the manner in which the cancer cells extend their tendrils into...
17.11.2015 | Event News
21.10.2015 | Event News
20.10.2015 | Event News
24.11.2015 | Trade Fair News
24.11.2015 | Trade Fair News
24.11.2015 | Life Sciences