Yellow fever (YF) is a mosquito-borne disease caused by the neurovirulent and viscerotropic YF virus (YFV). Fevers, nausea, body aches, and fatigue commonly characterize the disease, with around 15% of infected people entering fatal phases. The mosquitos that typically carry YFV roam over Africa and South America, where approximately 1 billion people among 46 countries are at risk. A live-attenuated vaccine, strain 17D, was developed in the 1930s and used ever since. However, cases of adverse events presented after the administration of YF vaccines. Additionally, certain groups cannot take the YF vaccine due to its contraindications. Previous advancements in understanding the YFV and developing the vaccine are attributable to the use of animal models. Model organisms are also critical in implementing current modifications to the YF vaccine. This review will discuss these topics in greater detail with a heavy emphasis on the contribution of animal models to the study of YF, along with alternative methods to maximizing global immunity against YF.
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