A Mouse Model of Yellow Fever Virus Infection for Study of Pathogenesis and Development of Vaccines and Therapeutics

Abstract

Yellow Fever (YF) is a mosquito-borne viral disease that is endemic in several African and South American countries. YF Virus (YFV) causes subclinical infections with mild and non-specific symptoms, to severe, potentially lethal illness. Despite the existence of efficient vaccines, epidemics continue to occur, mostly in Africa. One major drawback of the available YF vaccines is their method of preparation that is fastidious and have limits to produce high volumes of doses needed to respond to recurring epidemics. The best available animal models for YFV are Non-Human Primates (NHP) in which it causes a disease similar to human infection. However, the cost of NHP studies is a limit to preclinical studies. There are a few mouse models of YF. However, these models consist of genetically deficient rodents that are not the best for evaluating new vaccines or therapies. We have developed a mouse model of YFV infection based on the Swiss Webster out bred strain. We have tested several epidemic isolates and identified two strains that, when administrated by the intraperitoneal route, caused an acute infection leading to death. Interestingly, these YFV strains are lethal only when prepared from mouse brain and not when cultured on cell lines. We used this model to test the efficacy of the 17D YFV vaccine strain in protecting mice against lethal challenge showing that the model can be used to evaluate new YF vaccines and therapies.