Host-Pathogen Coevolution and the Emergence of Broadly Neutralizing Antibodies in Chronic Infections

PLoS Genet. 2016 Jul 21;12(7):e1006171. doi: 10.1371/journal.pgen.1006171. eCollection 2016 Jul.

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 between antibodies and 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 have relevance to vaccine design against HIV.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptive Immunity / genetics*
  • Antibodies, Neutralizing / genetics*
  • Antigens / immunology
  • Evolution, Molecular
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / immunology
  • Host-Pathogen Interactions
  • Humans
  • Models, Genetic

Substances

  • Antibodies, Neutralizing
  • Antigens

Grants and funding

“We acknowledge funding from the US National Science Foundation grants PHY-1305525 and PHY11-25915, the James S. McDonnell Foundation 21st century science initiative-postdoctoral program in complexity science / complex systems, the David and Lucile Packard Foundation, the U.S. Department of the Interior (D12AP00025), and the U.S. Army Research Office (W911NF-12-1-0552). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.”