| Abstract: |
| For many diseases, at various times after the primary infection, sequential infection can occur with diverse viral strains. Here we introduce a simple model that presents a balance between two distinct adaptive immune responses: cross-reactive responses derived from preexistent antibodies and specific antibodies generated during secondary infection. Our analytical and numerical results suggest that cross-reactive antibodies dominate the adaptive immune response when viral strains are similar, even if the initial cross-reactive response is sufficiently small; thus the waning period does not affect the ratio of adaptive to cross-reactive antibodies significantly. However, the waning period and antigenic similarity both matter to viral production and host damage, with greatest production and most damage occurring when the initial cross-reactive response is large and viruses are dissimilar. Moreover, adaptive immunity lowers disease severity, while a higher pathogen growth rate increases it, showing that disease outcome depends on both immune responses and pathogen traits. In addition, sequential infections with a circulating strain that is antigenically very similar to a previous infection may limit the hosts ability to mount a diverse portfolio of immune responses. Therefore, understanding how immune imprinting shapes the overall host immune response can be critical for effective protection during an epidemic. |
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