Dengue Research in NIAID Labs
Laboratory of Infectious Diseases
Respiratory Viruses Section
Brian R. Murphy, M.D., leads a research team that aims to develop a tetravalent, or four-part, vaccine that confers protection from all four types of dengue virus. Using a technique called reverse genetics, in which vaccines are made using the cloned DNA of dengue as opposed to wild viruses, Dr. Murphy and his team have developed several promising live attenuated vaccine candidates. They have also tested an effective tetravalent vaccine in non-human primates.
Early-stage clinical trials have shown that three of the four dengue virus vaccines (for dengue 1, dengue 2, and dengue 4) are safe and induce immunity. Most importantly, they will be inexpensive to manufacture, allowing them to be produced by manufacturers in developing countries where dengue viruses are prevalent. Clinical trials with two vaccine candidates against dengue 3 are underway.
The dengue vaccine candidates can reduce the level of virus transmission from humans to mosquitoes, as well as the virus’s ability to reproduce itself, or replicate, in the mosquito. Because dengue circulates from human to mosquito to human, eliminating transmission to the insect carriers will help ease the burden of disease, even among those not exposed directly to the vaccine.
Learn more about the Respiratory Viruses Section.
Molecular Viral Biology Section
Ching-Juh Lai, Ph.D., directs research activities to identify genes and functions of dengue viruses that determine infectivity and severity of disease. His goal is to define the mechanisms that allow the virus to reproduce, or replicate, using cultured cells and animal models. Strategies that exploit these mechanisms for weakening, or attenuating, dengue viruses could lead to development of new vaccines.
Dr. Lai and his team also study the antigen structures of the virus that are most effective in coaxing the immune system into generating neutralizing antibodies against dengue infection, but not antibodies that enhance infection; these antibodies are believed to be responsible for antibody-dependent enhancement (ADE) of dengue, which leads to more severe forms of dengue disease.
Dr. Lai and his team have studied chimpanzee antibodies that neutralize dengue virus. Because of the close relationship between chimpanzees and humans, these antibodies should help researchers analyze dengue virus infection and its antigenic structure, its mechanisms for invading cells, and possible strategies for short-term prevention. Dr. Lai’s section also works to identify chimpanzee antibodies that mediate ADE in vitro and in vivo and to develop strategies to prevent ADE.
Learn more about the Molecular Viral Biology Section.
Laboratory of Viral Diseases
Viral Pathogenesis Section
Ted C. Pierson, Ph.D., and his research group investigate how the proteins that cover dengue viruses direct the virus’s process for entering cells and how this process can be targeted by the immune response of the host. While antibodies can protect the host using several different mechanisms, including directly neutralizing infection, they also could worsen infection and disease in some circumstances.
Dr. Pierson’s studies on the biochemical and cellular factors that control antibody potency offer insight into the antibody response elicited by dengue virus infection or vaccination, help to identify correlates of protection, and may guide the development of safe and effective second-generation dengue vaccines.
Learn more about the Viral Pathogenesis Section.
back to top