Dynamic modeling of antibody repertoire reshaping in response to viral infections.

Abstract

For decades, research has largely focused on the generation of high-affinity, antigen-specific antibodies during viral infections. This emphasis has made it challenging for immunologists to systematically evaluate the mechanisms initiating humoral immunity in specific immune responses. In this study, we employ ordinary differential equations (ODE) to investigate the dynamic reshaping of the entire antibody repertoire in response to viral infections. Our findings demonstrate that the host's antibody atlas undergoes significant restructuring during these infections by the selective expansion of antibody pools with strong binding activity. The simulation results indicate that the ELISA (Enzyme-Linked Immunosorbent Assay) outcomes do not directly reflect the levels of specific neutralizing antibodies, but rather represent a quantitative response of the reshaped antibody repertoire following infection. Our model transcends traditional theories of immune memory, providing an explanation for the sustained presence of specific antibodies in the human body in long term. Additionally, our model extends to explore the mechanistic basis of the original antigenic sin, providing practical applications of our framework. One important application of this model is that it indicates that antibodies with a faster forward binding rate are more effective in preventing and treating associated viral infections compared to those with higher binding affinity.