# Eco-evolutionary dynamics of pathogen immune-escape: deriving a population-level phylodynamic curve

## TL;DR

This paper introduces a new model to study how immunity influences the evolution of viruses, particularly immune-escape variants, and how factors like seasonality and interventions affect this process.

## Contribution

The paper presents a novel analytic, stochastic framework that dynamically generates a population-scale phylodynamic curve.

## Key findings

- For seasonal pathogens, the timing of immune-escape variant emergence depends on case importation between regions.
- Non-pharmaceutical interventions and their lifting significantly affect the risk of viral escape variant emergence.
- The framework can help evaluate the impact of immunity, vaccine design, and interventions on viral evolution.

## Abstract

The phylodynamic curve (Grenfell et al. 2004 Science
303, 327–332 (doi:10.1126/science.1090727)) conceptualizes how immunity shapes the rate of viral adaptation in a non-monotonic fashion, through its opposing effects on viral abundance and the strength of selection. However, concrete and quantitative model realizations of this influential concept are rare. Here, we present an analytic, stochastic framework in which a population-scale phylodynamic curve emerges dynamically, allowing us to address questions regarding the risk and timing of the emergence of viral immune escape variants. We explore how pathogen- and population-specific parameters such as strength of immunity, transmissibility, seasonality and antigenic constraints affect the emergence risk. For pathogens exhibiting pronounced seasonality, we find that the timing of likely immune-escape variant emergence depends on the level of case importation between regions. Motivated by the COVID-19 pandemic, we probe the likely effects of non-pharmaceutical interventions (NPIs), and the lifting thereof, on the risk of viral escape variant emergence. Looking ahead, the framework has the potential to become a useful tool for probing how natural immunity, as well as choices in vaccine design and distribution and the implementation of NPIs, affect the evolution of common viral pathogens.