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!
Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH
Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
20.01.2017 | Awards Funding
20.01.2017 | Materials Sciences
20.01.2017 | Life Sciences