Title: B cells in shape space: a stochastic agent-based model of affinity maturation

 

Abstract: Affinity maturation—the process by which produced antibodies increase in affinity for antigen—occurs during the course of an immune response. Repeated exposures to the same antigen will produce antibodies of successively greater affinities, however, as antigen move away (in antigenic distance) from the initial strain, the ability of the body to cross-reactively neutralize the antigen decreases. This is a concern in the face of successive variants of concern (VOC) of SARS-CoV-2 that demonstrate an increase in antigenic distance from the original strain. Such VOCs would be less susceptible to any immune protection gained from vaccination and prior infection. We modeled adaptive immunity using an agent-based model (ABM) that considers B cells (naïve, plasma, memory), antibodies, and antigens. We represent receptor (B cells, antibodies) and epitope (antigens) proteins in Euclidean shape space, simulating binding between these agents based on Hamming distance. We also consider the formation of immune complexes—free antibodies bind to antigen which limits the antigen’s ability to infect more cells. In this seminar, I will discuss our model, parameterization efforts, and results in the context of SARS-CoV-2.