Dengue Virus Specific Immune Response: Implications for laboratory diagnosis and vaccine development
Dengue viruses (DENV 1-4) belong to the family Flaviviridae, genus Flavivirus. They are transmitted to humans through the bite of infected mosquitoes of the Aedes species. An estimated 100 million people are annually infected with DENV and over two billion people are at risk in acquiring DENV infection in tropical and subtropical regions of the world. Infection with DENV may be asymptomatic or may be characterized by a variety of clinical symptoms including mild dengue fever or more severe forms of disease characterized by haemorrhages which may lead to shock. Treatment of DENV infection is supportive but non-specific. The world-wide distribution of the mosquito vector as well as the high morbidity and mortality rates of DENV infection have led to the emergence of DENV as one of the most important public health problems world-wide. Laboratory diagnosis of DENV infection is based on virus isolation from cell cultures and/or detection of viral RNA, or on the detection of DENV specific immunoglobulin M (IgM) and IgG serum antibodies. Recent studies have revealed that serological diagnosis can be difficult due to crossreactions observed with other members of the genus Flavivirus. Despite several decades of research the pathogenesis of DENV infection is poorly understood. Antibody dependent enhancement (ADE) of infection has been associated with severe DENV disease outcome. Although ADE is at the basis of the predominant theory to explain different forms of severe DENV infections, it is now generally accepted that other factors such as virological, immunological and other host factors may play important roles in the pathogenesis of severe DENV disease. Theoretically, as for other arthropod-borne viral infections, prevention of DENV can be achieved either through vector control or through immunization strategies. Prevention of DENV through vector control is largely ineffective, expensive and with only temporary benefit. Several groups have attempted to develop a vaccine against DENV with limited success so far. A live attenuated tetravalent candidate vaccine against all four DENV serotypes has been developed and evaluated also in phase I and II human trials, but it is not yet licensed for public use. The lack of suitable animal models to test DENV disease has hampered the development of a safe and effective vaccine and extensive studies on the pathogenesis of DENV infections.
|Keywords||immunology, vaccine development, viruses|
|Promotor||A.D.M.E. Osterhaus (Ab)|
|Publisher||Erasmus University Rotterdam|
|Sponsor||Glaxo Smith Klein Biologicals , Osterhaus, Prof. Dr. A.D.M.E. (promotor) , World Health Organization|
Koraka, P.. (2007, September 27). Dengue Virus Specific Immune Response: Implications for laboratory diagnosis and vaccine development. Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/10532
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