Dynamic causal modelling of immune heterogeneity

TL;DR

This paper develops a dynamic causal model of immune response heterogeneity, using mean-field dynamics to simulate immune mechanisms and test hypotheses, with potential applications in immunological testing and vaccine assessment.

Contribution

It introduces a novel mean-field based model of immune response dynamics, formalizing hypotheses about resistance mechanisms and demonstrating its use in hypothesis testing and immunological assays.

Findings

Simulated immune response dynamics under various hypotheses.

Illustrated potential for rapid immunological testing.

Showed how the model can classify immune responses using Bayesian methods.

Abstract

An interesting inference drawn by some Covid-19 epidemiological models is that there exists a proportion of the population who are not susceptible to infection -- even at the start of the current pandemic. This paper introduces a model of the immune response to a virus. This is based upon the same sort of mean-field dynamics as used in epidemiology. However, in place of the location, clinical status, and other attributes of people in an epidemiological model, we consider the state of a virus, B and T-lymphocytes, and the antibodies they generate. Our aim is to formalise some key hypotheses as to the mechanism of resistance. We present a series of simple simulations illustrating changes to the dynamics of the immune response under these hypotheses. These include attenuated viral cell entry, pre-existing cross-reactive humoral (antibody-mediated) immunity, and enhanced T-cell dependent immunity. Finally, we illustrate the potential application of this sort of model by illustrating variational inversion (using simulated data) of this model to illustrate its use in testing hypotheses. In principle, this furnishes a fast and efficient immunological assay--based on sequential serology--that provides a (i) quantitative measure of latent immunological responses and (ii) a Bayes optimal classification of the different kinds of immunological response (c.f., glucose tolerance tests used to test for insulin resistance). This may be especially useful in assessing SARS-CoV-2 vaccines.