Constraints on pathogen evolution from order-dependent immunity*

Evolving pathogens are ubiquitous, and so it is of great interest to predict how intrinsic viral properties and population characteristics determine the emergence, extinction, and coexistence of distinct strains. Strain dynamics are mediated by cross-protective immunity, whereby exposure to one strain of a pathogen induces partial protection against infection by diverged strains. One challenge for predicting strain dynamics is that this protection is strongly influenced by the initial conditions - i.e. the identity of the first strain of exposure - a phenomenon known as original antigenic sin (OAS). This sets up an order dependence in the relationship between protection and strain exposure over time, with consequences for epidemic dynamics. In this talk, we propose a model of pathogen evolution which incorporates OAS into assumptions about immune memory creation and cross-protection. We derive new constraints on the successive strain replacement regime demonstrated by respiratory pathogens such as influenza and SARS-CoV-2, implying a speed limit on the rate of evolution for such pathogens as well as constraints on diversity. This is an example of a phenomenon that cannot be replicated in models lacking OAS, and thus argues for the importance of incorporating OAS into future work.