Animal models for dengue vaccine development and testing

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

Pigs have several features that make them attractive animal models. They are physiologically similar to humans and are less expensive to obtain and house than NHPs. In addition, a large number of immunological reagents are available for swine models. Yucatan miniature swine models are advantageous in that they possess physiological and immunological response similarities to human. This swine model has similar cardiovascular, immunologic, metabolic, and skin physical properties, and these aspects are important in studying DHF since DENV is known to affect these systems. Also, production of antibody and immune response of Yucatan miniature pig and of human are similar. This pig model is known to be susceptible to flavivirus family, such as Japanese encephalitis, yellow fever virus, murray valley encephalitis, etc. [30] . In a study, porcine model was subcutaneously infected with 10 7 PFU of DENV type 1, and induced viremia, anti-dengue IgM, IgG, and neutralizing antibodies in all pigs, However, again, none of the pigs showed any signs or symptoms. Secondary infection of 10 7 PFU Dengue-1 virus induced viremia and IgM in a lower amount than in primary infection, while IgG and neutralizing antibodies were elevated. The secondary infection had induced extensive maculopapular rashes, and it was consistent with human dengue-related rash. Infecting swine model with DENV type 1 through intravenous injection, symptoms developed skin rash and dermal edema ( Table 1) . DENV-containing immune complex were founded in the pig serum, which suggests the possibility of ADE-like phenomenon. Additionally, vaccine test against DENV type 1 developed robust neutralizing immune response against DENV [31] . Although such results appear promising, swine model for DENV still has some limitations of being asymptomatic, and this evokes further studies using other types of DENV.