Numerical analysis of the origin of immunodominance and original antigenic sin

We introduce a quasi-species model to analyze the B-cell immune response to mutating diseases. The naive and the memory B-cell immune response dynamics are represented by a quasi-species evolution model. Using a combination of exponential and random fitness functions for the quasi-species model, we find that the B cell immune response is biased toward the higher affinity epitope during the primary immune response (immunodominance) and that for the antigen with high mutation rate (≳0.4), the memory B cells may increase susceptibility to the mutated epitope during the secondary immune response (original antigenic sin). These results suggest that immunodominance stems from the sharp global maximum in the fitness landscape and that the original antigenic sin stems from the localization of the previous global maximum to a local maximum in the rough fitness landscape due to a mutation of the epitope. This information may provide guidance for vaccine development against rapidly mutating diseases.