Host-pathogen coevolution and the emergence of broadly neutralizing antibodies in chronic infections

TL;DR

This paper presents a mathematical model of host-pathogen coevolution, focusing on antibody-antigen interactions in chronic infections like HIV, to understand how broadly neutralizing antibodies emerge and inform vaccine design.

Contribution

It introduces a novel analytical framework for studying coevolution dynamics, identifying key parameters and signatures that drive the emergence of broadly neutralizing antibodies.

Findings

Identifies critical parameters influencing antibody-antigen affinity distribution.

Defines measurable signatures of coevolution and adaptation.

Derives conditions favoring the emergence of broadly neutralizing antibodies.

Abstract

The vertebrate adaptive immune system provides a flexible and diverse set of molecules to neutralize pathogens. Yet, viruses such as HIV can cause chronic infections by evolving as quickly as the adaptive immune system, forming an evolutionary arms race. Here we introduce a mathematical framework to study the coevolutionary dynamics of antibodies with antigens within a host. We focus on changes in the binding interactions between the antibody and antigen populations, which result from the underlying stochastic evolution of genotype frequencies driven by mutation, selection, and drift. We identify the critical viral and immune parameters that determine the distribution of antibody-antigen binding affinities. We also identify definitive signatures of coevolution that measure the reciprocal response between antibodies and viruses, and we introduce experimentally measurable quantities that quantify the extent of adaptation during continual coevolution of the two opposing populations. Using this analytical framework, we infer rates of viral and immune adaptation based on time-shifted neutralization assays in two HIV-infected patients. Finally, we analyze competition between clonal lineages of antibodies and characterize the fate of a given lineage in terms of the state of the antibody and viral populations. In particular, we derive the conditions that favor the emergence of broadly neutralizing antibodies, which may be useful in designing a vaccine against HIV.