The role of anti-flavivirus humoral immune response in protection and pathogenesis.

Flavivirus infections are a public health threat in the world that requires the development of safe and effective vaccines. Therefore, the understanding of the anti-flavivirus humoral immune response is fundamental to future studies on flavivirus pathogenesis and the design of anti-flavivirus therapeutics. This review aims to provide an overview of the current understanding of the function and involvement of flavivirus proteins in the humoral immune response as well as the ability of the anti-envelope (anti-E) antibodies to interfere (neutralizing antibodies) or not (non-neutralizing antibodies) with viral infection, and how they can, in some circumstances enhance dengue virus infection on Fc gamma receptor (FcγR) bearing cells through a mechanism known as antibody-dependent enhancement (ADE). Thus, the dual role of the antibodies against E protein poses a formidable challenge for vaccine development. Also, we discuss the roles of antibody binding stoichiometry (the concentration, affinity, or epitope recognition) in the neutralization of flaviviruses and the "breathing" of flavivirus virions in the humoral immune response. Finally, the relevance of some specific antibodies in the design and improvement of effective vaccines is addressed.