National Institute of Allergy and Infectious Diseases (NIAID) scientists are developing promising dengue virus vaccine candidates, with the goal of creating a vaccine that is protective against all four dengue virus serotypes.
Preclinical and early phase clinical testing has been encouraging, warranting their further development for use as live attenuated vaccine candidates.
Typically spread through mosquitos, dengue virus infection can lead to dengue hemorrhagic fever and, in severe cases, death.
In recent years dengue fever (DF) has become a major international health problem affecting tropical and sub-tropical regions around the world – especially urban and peri-urban areas. The geographic distribution of dengue, the frequency of epidemic cycles, and the number of cases of dengue have increased sharply during the last two decades. In addition, the frequency of a potentially lethal complication of dengue, called dengue haemorrhagic fever (DHF) has begun to occur on a regular basis in countries where only dengue occurred previously.
Dengue fever is caused by four distinct but closely related dengue viruses called serotypes (DEN-1, DEN-2, DEN-3, and DEN-4) and transmitted to humans through the bites of infected mosquitos (Aedes aegypti is the primary vector).
Dengue fever is a severe flu-like illness that affects infants, young children and adults, but rarely causes death. Symptoms vary according to age. Infants and young children may be asymptomatic or have undifferentiated fever and rash, whereas older children or adults are more likely to have a more severe set of symptoms including high fever that starts quickly, sometimes with two peaks, and/or severe headache, pain behind the eyes, muscle and joint pains, nausea and vomiting and rash. Infection with dengue confers immunity to infection with the same dengue serotype, but aside from short-lived protection does not prevent infection with other serotypes.
DHF is a life threatening complication of dengue characterized by high fever lasting 2-7 days, haemorrhagic phenomena (including vascular leakage of plasma), low numbers of platelets and sometimes circulatory failure. The condition of some patients progresses to shock. This is known as dengue shock syndrome (DSS), which could be rapidly fatal if appropriate volume replacement therapy is not administered promptly. Without proper treatment, DHF case fatality rates can exceed 20%. With modern intensive supportive therapy, it can be reduced to less than 1%.
While the mechanisms that cause DHF are not completely understood, it is widely accepted that antibodies from previous dengue infections can predispose some individuals to develop DHF when infected by a second dengue serotype. Thus the co-circulation of several different dengue serotypes in a geographical area favours the occurrence of DHF in that area.