Antibody-Mediated Neutralization of West Nile Virus: Factors that Govern Neutralization Potency

Flaviviruses are complex immunogens that elicit antibodies of varying specificity and with a spectrum of functional properties. Flavivirus virions are covered by a dense array of envelope (E) proteins that mediate steps of the virus entry pathway and are a primary target of neutralizing antibodies. The development of virus-specific antibodies is a critical aspect of protection against flavivirus infection and a major goal of ongoing efforts to produce vaccines against flaviviruses of clinical importance, such as the West Nile virus. In this chapter, we will review current models that describe how antibodies engage flaviviruses and block infection. Recent insight into the relationships that govern where antibodies bind virions and how this impacts the potency and mechanisms of neutralization of antibodies have been driven in part by insights from the structural biology of flaviviruses. The factors that define antibody potency will be discussed with a focus on the stoichiometric requirements for neutralization.