A Dynamic Landscape for Antibody Binding Modulates Antibody-Mediated Neutralization of West Nile Virus

• DOI: 10.1371/journal.ppat.1002111
• Publication Date: 2011-06-30T21:22:45Z
• Authors: Kimberly A. Dowd; Christiane A. Jost; Anna P. Durbin; Stephen S. Whitehead; Theodore C. Pierson
• Keywords: Flavivirus; Antibody-dependent enhancement

Neutralizing antibodies are a significant component of the host's protective response against flavivirus infection. Neutralization flaviviruses occurs when individual virions engaged by with stoichiometry that exceeds required threshold. From this "multiple-hit" perspective, neutralizing activity is governed affinity which it binds its epitope and number times determinant displayed on surface virion. In study, we investigated time-dependent changes in fate West Nile virus (WNV) decorated antibody solution. Experiments well-characterized monoclonal (MAb) E16 revealed increase neutralization over time could not be explained kinetics binding, virion aggregation, or action complement. Additional kinetic experiments using fusion-loop specific MAb E53, has limited because recognizes relatively inaccessible mature virions, identified role "breathing" regulating activity. Remarkably, E53 neutralized WNV time- temperature-dependent manner. This phenomenon was confirmed studies large panel MAbs for epitopes each domain envelope protein, sera from recipients live attenuated vaccine, dengue virus. Given enough time, inhibition infection observed even very limited, no standard assays. Together, our data suggests structural dynamics impacts antibody-mediated via exposure otherwise epitopes, allowing to dock sufficient neutralization.