Princeton: Pathogen Immune-Escape Dynamics

Bjarke F. Nielsen and colleagues at Princeton introduce a mathematical framework to understand how pathogen evolution, specifically immune escape, is influenced by population-level immunity and transmission dynamics.  They developed a model to derive a population-level phylodynamic curve, a concept illustrating the relationship between immunity strength and the rate of viral adaptation.  The researchers explore how factors like the strength and duration of immunity, transmissibility, seasonality, and interventions impact the risk and timing of immune escape variant emergence.  They also consider the differences between leaky and waning immunity and the role of antigenic constraints, offering a tool to assess immune escape risk for various pathogens and inform public health strategies:

·      Leaky' (partially susceptibility-reducing) immunity gives rise to a non-monotonic immunity/escape risk relation, but purely waning all-or-nothing immunity does not.

·      If immunity is leaky, the presence of waning does not substantially change the immunity/escape risk relation.

·      In seasonally driven outbreaks, the bulk of the escape risk occurs in the initial stages of each outbreak. Still, case imports from regions with year-round circulation can shift the bulk of the escape risk to the low-incidence trough period.

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The proposed framework can be applied to empirical data to evaluate the risk of viral immune escape variant emergence. It can be used for comparative analysis across pathogens to understand their propensity for rapid evolution and inform surveillance and intervention strategies.

Nielsen BF, Saad-Roy CM, Metcalf CJE, Viboud C, Grenfell BT. Eco-evolutionary dynamics of pathogen immune-escape: deriving a population-level phylodynamic curve. J R Soc Interface. 2025 Apr;22(225):20240675. doi: 10.1098/rsif.2024.0675. Epub 2025 Apr 2. PMID: 40172571; PMCID: PMC11963905.

https://royalsocietypublishing.org/doi/10.1098/rsif.2024.0675