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!
Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz
Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences