Peptides as Therapeutic Agents for Dengue Virus

Chew, Miaw-Fang; Poh, Keat-Seong; Poh, Chit-Laa

One of the strategies that has been undertaken to halt DENV infection is by vector control. Aedes aegypti and Aedes albopictus are the primary transmission vectors for DENV [8] . Strategies such as fogging and the release of genetically modified mosquitoes which could lead to the production of fewer progenies [9] have failed to lessen the mosquito population, as witnessed by the emergence of new dengue cases in places that were dengue-free or had less dengue cases in the past [10] [11] [12] . While active research on vaccine development for dengue has been ongoing for the past few decades, the development of vaccines has been held back by several challenges. The major constraints for dengue vaccine development include the lack of good animal models, the complexity of developing a vaccine against all four antigenically distinct DENV serotypes, as well as the need to achieve balanced tetravalent responses that could Ivyspring International Publisher exhibit significant immunity against all four viruses without the adverse effects of ADE or original antigenic sin [13] . The first dengue vaccine, Dengvaxia®, (CYD-TDV, chimeric yellow fever virus-tetravalent dengue vaccine) developed by Sanofi Pasteur was licensed in December 2015 in Mexico. It is a live-attenuated tetravalent vaccine comprising structural proteins (pre-membrane and envelope proteins) of DENV based on the yellow fever 17D virus backbone [14, 15] . The approved regimen involves three doses, given at the 0 th , 6 th and 12 th months, for individuals between 9-45 years of age. Outcomes from phase III clinical trials showed that the vaccine successfully reduced dengue hospitalizations by 80%. However, its average efficacy against DENV was low, especially against DENV-1 at approximately 50% and against DENV-2 at 39%. Its average efficacy against DENV-3 and DENV-4, meanwhile, was slightly higher at 75% and 77%, respectively [16, 17] . Furthermore, previous clinical trials revealed that CYD-TDV vaccination caused elevated risks of hospitalization for children less than nine years of age [18] . The World Health Organization has therefore recommended the use of CYD-TDV vaccine only in countries where epidemiological data indicated a high burden of dengue [19] .