SMILE

Stochastic Models for the Inference of Life Evolution

SMILE | Stochastic Models for the Inference of Life Evolution | Collège de France

Presentation

SMILE is an interdisciplinary research group gathering mathematicians, bio-informaticians and biologists.
SMILE is affiliated to the Institut de Biologie de l'ENS, in Paris.
SMILE is hosted within the CIRB (Center for Interdisciplinary Research in Biology) at Collège de France.
SMILE is supported by Collège de France and CNRS.
Visit also our homepage at CIRB.

Directions

SMILE is hosted at Collège de France in the Latin Quarter of Paris. To reach us, go to 11 place Marcelin Berthelot (stations Luxembourg or Saint-Michel on RER B).
Our working spaces are rooms 107, 121 and 122 on first floor of building B1 (ask us for the code). Building B1 is facing you upon exiting the traversing hall behind Champollion's statue.

Contact

You can reach us by email (amaury.lambert - at - college-de-france.fr) ; (guillaume.achaz - at - college-de-france.fr) or (smile - at - listes.upmc.fr).

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Publication

2022

The speed of vaccination rollout and the risk of pathogen adaptation

Vaccination is expected to reduce disease prevalence and to halt the spread of epidemics. But pathogen adaptation may erode the efficacy of vaccination and challenge our ability to control disease spread. Here we examine the influence of the speed of vaccination rollout on the overall risk of pathogen adaptation to vaccination. We extend the framework of evolutionary epidemiology theory to account for the different steps leading to adaptation to vaccines: (1) introduction of a vaccine-escape variant by mutation from an endemic wild-type pathogen, (2) invasion of this vaccine-escape variant in spite of the risk of early extinction, (3) spread and, eventually, fixation of the vaccine-escape variant in the pathogen population. We show that the risk of pathogen adaptation is maximal for intermediate speed of vaccination rollout. On the one hand, slower rollout decreases pathogen adaptation because selection is too weak to avoid early extinction of the new variant. On the other hand, faster rollout decreases pathogen adaptation because it reduces the influx of adaptive mutations. Hence, vaccinating faster is recommended to decrease both the number of cases and the likelihood of pathogen adaptation. We also show that pathogen adaptation is driven by its basic reproduction ratio, the efficacy of the vaccine and the effects of the vaccine-escape mutations on pathogen life-history traits. Accounting for the interplay between epidemiology, selection and genetic drift, our work clarifies the influence of vaccination policies on different steps of pathogen adaptation and allows us to anticipate the effects of public-health interventions on pathogen evolution.Significance statement Pathogen adaptation to host immunity challenges the efficacy of vaccination against infectious diseases. Are there vaccination strategies that limit the emergence and the spread of vaccine-escape variants? Our theoretical model clarifies the interplay between the timing of vaccine escape mutation events and the transient epidemiological dynamics following the start of a vaccination campaign on pathogen adaptation. We show that the risk of adaptation is maximized for intermediate vaccination coverage but can be reduced by a combination of non pharmaceutical interventions and maximizing the speed of the vaccination rollout. These recommendations may have important implications for the choice of vaccination strategies against the ongoing SARS-CoV-2 pandemic.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis study was funded by a grant from CNRS MITI to SG.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesI confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThis is a theoretical study.

Publication

2018

Coagulation-transport equations and the nested coalescents

The nested Kingman coalescent describes the dynamics of particles (called genes) contained in larger components (called species), where pairs of species coalesce at constant rate and pairs of genes coalesce at constant rate provided they lie within the same species. We prove that starting from \$$rn\$$ species, the empirical distribution of species masses (numbers of genes\$$/n\$$) at time \$$t/n\$$ converges as \$$n\to\infty\$$ to a solution of the deterministic coagulation-transport equation $$ \partial_t d \ = \ \partial_x ( \psi d ) \ + \ a(t)\left(d\star d - d \right), $$ where \$$\psi(x) = cx^2\$$, \$$\star\$$ denotes convolution and \$$a(t)= 1/(t+\delta)\$$ with \$$\delta=2/r\$$. The most interesting case when \$$\delta =0\$$ corresponds to an infinite initial number of species. This equation describes the evolution of the distribution of species of mass \$$x\$$, where pairs of species can coalesce and each species' mass evolves like \$$\dot x = -\psi(x)\$$. We provide two natural probabilistic solutions of the latter IPDE and address in detail the case when \$$\delta=0\$$. The first solution is expressed in terms of a branching particle system where particles carry masses behaving as independent continuous-state branching processes. The second one is the law of the solution to the following McKean-Vlasov equation $$ dx_t \ = \ - \psi(x_t) \,dt \ + \ v_t\,\Delta J_t $$ where \$$J\$$ is an inhomogeneous Poisson process with rate \$$1/(t+\delta)\$$ and \$$(v_t; t\geq0)\$$ is a sequence of independent rvs such that \$$\mathcal L(v_t) = \mathcal L(x_t)\$$. We show that there is a unique solution to this equation and we construct this solution with the help of a marked Brownian coalescent point process. When \$$\psi(x)=x^\gamma\$$, we show the existence of a self-similar solution for the PDE which relates when \$$\gamma=2\$$ to the speed of coming down from infinity of the nested Kingman coalescent.

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