Sequence Space Localization in the Immune System Response to Vaccination and Disease

TL;DR

This paper presents a model explaining how the immune system's response to vaccination and disease is localized in antibody sequence space, leading to phenomena like original antigenic sin, especially in rapidly mutating diseases.

Contribution

It introduces a novel protein evolution model linking sequence space localization to immune response limitations and phenomena like original antigenic sin.

Findings

Localization of immune response in antibody sequence space observed.

Model explains increased susceptibility due to original antigenic sin.

Applicable to diseases with high mutation rates like influenza.

Abstract

We introduce a model of protein evolution to explain limitations in the immune system response to vaccination and disease. The phenomenon of original antigenic sin, wherein vaccination creates memory sequences that can \emph{increase} susceptibility to future exposures to the same disease, is explained as stemming from localization of the immune system response in antibody sequence space. This localization is a result of the roughness in sequence space of the evolved antibody affinity constant for antigen and is observed for diseases with high year-to-year mutation rates, such as influenza.