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

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

Otherness in self and organisations:Kafka's The Metamorphosis to stir moral reflection

Informed by Jung’s analytical psychology, this chapter discusses Kafka’s short-story The metamorphosis in relation to moral reflection on organisational life. Adopting the view that fiction offers a promising path to engage the reader’s imagination and reflection on moral issues, I explore such process in light of The metamorphosis. I argue that this story not only outlines important moral issues of relevance to workers in modern organisations, but is also particularly effective in eliciting a reaction from the reader which calls for further analysis. Reading about Gregor Samsa’s transformation precludes indifference; instead, it asks us to reflect on our own moral values and behaviours, and to ponder on our tolerance for what is ‘other’. In turn, this enhanced knowledge and understanding of ourselves help explore ethical issues in organisations in a more subjective, creative and holistic manner