Animal models for dengue vaccine development and testing

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

Rodent models are generally used as a first step for pre-clinical development of vaccines since they cost significantly less than other models, such as non-human primate (NHP) models. However, immune responses in mouse models can be underestimated since the DENV replication rate in mice is low. In addition, immunocompromised mouse models, one of the most frequently used rodent models, lack interferon (IFN)-α/β and -γ receptors; therefore, they cannot develop full immune responses (Table 1) . Currently available immunocompetent mice models include the BALB/c, A/J, and AG129 models. Although no humanized BALB/c mouse models are available, they are important models because they are widely used, provide adequate relevance to dengue infection, and enable evaluation of innate systems or vaccine/antiviral studies. The A/J mouse models are similar to the BALB/c models in that they are easily accessible and show better proximity to humans in terms of DENV infection and their feasibility for evaluating the innate response in vaccine/antiviral studies. AG129 models are similar to BALB/c and A/J mice in terms of their relevance to DENV infection and their availability, and they provide superior information when evaluating innate immunity and in vaccine studies ( Table 2 ). The currently available immunodeficient/knockout mouse models include SCID mice reconstituted with human peripheral blood lymphocytes (SCID-PBL), SCID mice transplanted with human cell lines (SCID cell lines), and NOD/SCIDhu mouse models [12] . SCID-PBL models are not sufficient for evaluation of the innate system compared to immunocompetent models, although they show great relevance to dengue infection and are a better model for the evaluation of vaccine and antiviral agents than immunocompetent mouse models. SCID cell line models are more widely available than SCID-PBL models; however, their applicability to dengue infection is limited when compared to SCID-PBL models. NOD/ SCID-hu models are more relevant for DENV infection than SCID-PBL models, and provide the best outcomes in studies of DENV infection and the evaluation of innate immune responses to vaccines and antiviral agents ( Table 2) .