The results challenge the current state of dengue vaccine research, which is based on studies in mice and targets a different region of the virus.
"In the past researchers have relied on mouse studies to understand how the immune system kills dengue virus and assumed that the mouse studies would apply to people as well," said senior study author Aravinda M. de Silva, PhD, associate professor of microbiology and immunology at the UNC School of Medicine.
"Our study for the first time shows what region the immune system of humans target when they are fighting off the virus. The region on the virus targeted by the human immune system is quite different from the region targeted by mice."
The new research, which will appear online during the week of April 11-14, 2012 in the Proceedings of the National Academy of Sciences, was performed using blood cells from local travelers infected with dengue virus.
The global incidence of dengue has grown dramatically in recent decades, putting about half of the world's population at risk. Creation of a vaccine is complicated by the fact that there are four distinct, but closely related forms of the virus that cause dengue. Once people have recovered from infection with one form of the virus, they have lifelong immunity against that form.
But if they become infected with one of the other three forms of the virus, they increase their chances of developing the severe bleeding and sometimes fatal dengue hemorrhagic fever and dengue shock syndrome. The leading theory to explain why some people develop dengue hemorrhagic fever is that under some conditions the human immune response can actually enhance the virus and disease during a second infection.
"This is a huge issue for vaccine development," said lead study author Ruklanthi de Alwis, a graduate student in de Silva's lab. "We have to figure out a way to develop dengue vaccines that induce the good response that protects against infection, at the same time avoiding the bad response that enhances disease."
de Alwis looked at a particular subset of the immune response – specialized molecules called antibodies. UNC investigators identified 7 local individuals who had contracted dengue during travel to an endemic region and sent blood cells from these individuals to Vanderbilt School of Medicine. Drs. Scott Smith and James Crowe at Vanderbilt were able to isolate dengue antibodies from these cells for further study at UNC. The team found that instead of binding to small fragments of the virus -- like mouse antibodies do -- human antibodies that neutralized the virus bound to a complex structure that was only present on a completely assembled dengue virus.
"Though this is the first time this phenomenon has been shown with dengue, just last year there were a number of studies showing that antibodies recognize similar complex epitopes in both HIV and West Nile Virus," said de Alwis. "New vaccines as well as those already in the pipeline will need to be assessed to see if they bind just a small fragment or the whole virus, which may determine whether or not they work in humans."
The research was funded by the National Institute of Allergy and Infectious Diseases, the Southeastern Regional Center for Biodefense and Emerging Infections and a Pediatric Dengue Vaccine Initiative Targeted Research Grant.
Study co-authors from UNC were Nicholas P. Olivarez; William B. Messer; Jeremy P. Huynh; M. P. B. Wahala; and Ralph S. Baric
Les Lang | EurekAlert!
Developing a digital holography-based multimodal imaging system to visualize living cells
03.06.2020 | Kobe University
Possible physical trace of short-term memory found
03.06.2020 | Institute of Science and Technology Austria
An analysis of more than 200,000 spiral galaxies has revealed unexpected links between spin directions of galaxies, and the structure formed by these links...
Two prominent X-ray emission lines of highly charged iron have puzzled astrophysicists for decades: their measured and calculated brightness ratios always disagree. This hinders good determinations of plasma temperatures and densities. New, careful high-precision measurements, together with top-level calculations now exclude all hitherto proposed explanations for this discrepancy, and thus deepen the problem.
Hot astrophysical plasmas fill the intergalactic space, and brightly shine in stellar coronae, active galactic nuclei, and supernova remnants. They contain...
In living cells, enzymes drive biochemical metabolic processes enabling reactions to take place efficiently. It is this very ability which allows them to be used as catalysts in biotechnology, for example to create chemical products such as pharmaceutics. Researchers now identified an enzyme that, when illuminated with blue light, becomes catalytically active and initiates a reaction that was previously unknown in enzymatics. The study was published in "Nature Communications".
Enzymes: they are the central drivers for biochemical metabolic processes in every living cell, enabling reactions to take place efficiently. It is this very...
Early detection of tumors is extremely important in treating cancer. A new technique developed by researchers at the University of California, Davis offers a significant advance in using magnetic resonance imaging to pick out even very small tumors from normal tissue. The work is published May 25 in the journal Nature Nanotechnology.
researchers at the University of California, Davis offers a significant advance in using magnetic resonance imaging to pick out even very small tumors from...
Microelectronics as a key technology enables numerous innovations in the field of intelligent medical technology. The Fraunhofer Institute for Biomedical Engineering IBMT coordinates the BMBF cooperative project "I-call" realizing the first electronic system for ultrasound-based, safe and interference-resistant data transmission between implants in the human body.
When microelectronic systems are used for medical applications, they have to meet high requirements in terms of biocompatibility, reliability, energy...
19.05.2020 | Event News
07.04.2020 | Event News
06.04.2020 | Event News
03.06.2020 | Medical Engineering
03.06.2020 | Physics and Astronomy
03.06.2020 | Physics and Astronomy