Speaker
Description
Flaviviruses such as Dengue, Zika, Yellow Fever and West Nile virus represent major global public health threats. Envelope (E) proteins on the viral surface mediate host-cell attachment and membrane fusion. These 180 E proteins are arranged in a highly ordered geometry that shapes epitope accessibility and antibody binding.
Neutralization of flaviviruses is primarily mediated by monoclonal antibodies (mAb) targeting the E protein in an interplay between mAb affinity, epitope accessibility, and the number and organization of bound mAb.
We present preliminary results on a mathematical model of seroneutralization. We model virus–antibody interactions as a stochastic binding process that accounts for epitope spatial organization and occupancy on the viral surface. We include conformational transitions of the E protein and viral “breathing” dynamics, which modulate epitope accessibility and constrain binding kinetics. By introducing these structural and dynamical constraints, our approach aims to provide a mechanistic interpretation of neutralization curves grounded in the geometry and physics of the virion.
In parallel, we have developed a database of seroneutralization data for many measurements from mAbs, cells and flaviviruses. Using this resource, we explore mechanistic links between microscopic binding parameters and the shape of neutralization curves. Our framework aims to account for key features observed experimentally, including partial neutralization and neutralization by antibody mixtures.
This approach is designed to bridge quantitative modeling with practical questions in public health, including antibody-dependent enhancement (ADE) and the interpretation of polyclonal immune responses.
