Structure-Function of the Yellow Fever Virus Envelope Protein: Analysis of Antibody Epitopes.

Yellow fever virus (YFV) is the prototype member of the genus , which contains more than 60 positive-sense, single-stranded RNA viruses, many of which are considered public health threats. YF disease is controlled by a live attenuated vaccine, 17D, which was generated empirically through serial passage of the wild-type (WT) strain Asibi in chicken tissue. The vaccine, which has been used for over 80 years, is considered to be one of the safest and most effective live attenuated vaccines. It has been shown that the humoral immune response is essential to a positive disease outcome during infection. As such, the neutralizing antibody response and its correlation to long-term protection are a critical measure of 17D efficacy. The primary target of these antibodies is the envelope (E) protein, which is the major component of the virion. Monoclonal antibodies can distinguish WT strain Asibi and vaccine strain 17D by many different measures, including physical binding, hemagglutination inhibition, neutralization, and passive protection. This makes the WT-vaccine pair ideal candidates to study the structure-function relationship of the E protein in the attenuation and immunogenicity of flaviviruses. In this study, we provide an overview of structure-function of YFV E protein and its involvement in protective immunity.