Development of Dengue Vaccines: The Role of Animal Models

Dengue virus remains the most important arbovirus worldwide, and dengue disease poses a significant public health threat. Infection by one dengue serotype does not produce life-long protection against the other three serotypes, and severe disease may be due to non/poorly-neutralizing antibodies to heterologous or homologous dengue serotypes. As such, development, validation, and implementation of a protective vaccine against all four serotypes of dengue virus are considered to be the best approach for control of dengue disease. The Sanofi Pasteur Dengvaxia® dengue vaccine has been licensed in several endemic countries. However, it is clear that additional vaccine candidates are needed as the Dengvaxia® vaccine has several limitations including: (i) reduced efficacy in flavivirus naïve individuals; (ii) potential safety issues in naïve individuals; and (iii) a delivery regimen of three shots over a 12 month period. The limitation in our current understanding of dengue vaccine efficacy and dengue disease pathogenesis can in part be attributed to the lack of an ideal animal model for testing candidate vaccines. Importantly, improved dengue vaccine development can be addressed by better small animal models for testing dengue vaccine candidates and understanding dengue disease immunopathology. This review will assess the variety of animal models that exist for testing dengue vaccine candidates including, non-human primates, wild type and non-wild type mice, and humanized mice.