Animal models for dengue vaccine development and testing

Na, Woonsung; Yeom, Minjoo; Choi, Il-Kyu; Yook, Heejun; Song, Daesub

The immunology and pathology of DENV have not yet been elucidated, and this has limited the development of vaccines and effective therapeutics. Since 1940, when the development of DENV vaccines and treatments began, preclinical testing has not provided sufficient evidence for efficacy or accurate toxicity profiles at the clinical trial stage. Dengvaxia, the first DENV vaccine (developed by Sanofi), is a quadrivalent vaccine that was marketed in five countries, including Brazil, beginning in June 2016. However, its efficacy is only about 60%, which is less effective than that of other vaccines for diseases such as measles and poliomyelitis, which are more than 95% effective [6, 7] . Children under the age of 9 years and adults over the age of 45 years, the main victims of dengue fever, are not eligible to receive Dengvaxia due to unexplained side effects [8] . In addition, it has been shown to have insufficient effects on serotype 2 infection due to interference between serotypes [9] . Furthermore, a component of the vaccine, the non-structural protein of the yellow fever virus, induces a Tcell reaction to yellow fever rather than an antibody response to DENV [10] . A clinical trial of about 30,000 people conduct-ed in 10 countries showed that the vaccine may cause serious symptoms in patients [11] . The different clinical outcomes of vaccine administration, such as low efficacy and unexplained side effects, appear to result from the lack of an established disease model for testing the safety and efficacy.