Predicting protein evolution in vitro by phage escape technology

Abstract

The relationship between host and pathogen is inherently dynamic at the genetic level. A plethora of host defensive systems have evolved to counteract and/or eliminate invading pathogens. These strategies exert selection pressure upon the pathogen, leading to the emergence of mechanisms to combat the host including immune evasion and resistance. Consequently, effective control of rapidly evolving diseases is contingent on the ability to predict pathogen evolution prior to the emergence of resistant phenotypes. Highlighted in this article is a bacteriophage-based technology capable of screening hundreds of millions of binding events simultaneously at single molecule resolution, thus providing an in vitro mimetic of protein evolution. This technology, termed phage escape, can be utilized to model the evolution of proteins in the presence of antibodies or other selective pressure, providing a predictive solution to the coevolution of antigens and the immune system. Foresight into the evolutionary path of an antigen and subsequent neutralization strategies can facilitate more efficacious vaccination formulation and have important implications in the treatment of a range of evolving diseases, including viral infections and cancer.