Flaviviruses are a group of positive-stranded RNA viruses that cause a spectrum
of severe illnesses globally in more than 50 million individuals each year.
While effective vaccines exist for three members of this group (yellow fever,
Japanese encephalitis, and tick-borne encephalitis viruses), safe and effective
vaccines for several other flaviviruses of clinical importance, including West
Nile and dengue viruses, remain in development. An effective humoral immune
response is critical for protection against flaviviruses and an essential goal
of vaccine development. The effectiveness of virus-specific antibodies in vivo
reflects their capacity to inhibit virus entry and spread through several
mechanisms, including the direct neutralisation of virus infection. Recent
advances in our understanding of the structural biology of flaviviruses, coupled
with the use of small-animal models of flavivirus infection, have promoted
significant advances in our appreciation of the factors that govern antibody
recognition and inhibition of flaviviruses in vitro and in vivo. In this review,
we discuss the properties that define the potency of neutralising antibodies and
the molecular mechanisms by which they inhibit virus infection. How recent
advances in this area have the potential to improve the development of safe and
effective vaccines and immunotherapeutics is also addressed.