An Immunoproteomic Survey of the Antibody Landscape: Insights and Opportunities Revealed by Serological Repertoire Profiling.

Steven Ionov,Jiwon Lee

doi:10.3389/fimmu.2022.832533

Abstract

Immunoproteomics has emerged as a versatile tool for analyzing the antibody repertoire in various disease contexts. Until recently, characterization of antibody molecules in biological fluids was limited to bulk serology, which identifies clinically relevant features of polyclonal antibody responses. The past decade, however, has seen the rise of mass-spectrometry-enabled proteomics methods that have allowed profiling of the antibody response at the molecular level, with the disease-specific serological repertoire elucidated in unprecedented detail. In this review, we present an up-to-date survey of insights into the disease-specific immunological repertoire by examining how quantitative proteomics-based approaches have shed light on the humoral immune response to infection and vaccination in pathogenic illnesses, the molecular basis of autoimmune disease, and the tumor-specific repertoire in cancer. We address limitations of this technology with a focus on emerging potential solutions and discuss the promise of high-resolution immunoproteomics in therapeutic discovery and novel vaccine design.

Highlights

The discovery of a substance in serum with the ability to protect against disease dates back to Emil von Behring and Shibasaburo Kitasato [1]; just a year later, Paul Ehrlich made the first reference to ‘Antikörper’, or antibodies, in an 1891 report [2]
Though serology remains essential in the Serological Repertoire Profiling Across Diseases present-day study of antibody responses [10] and gives critical insights into the global immune repertoire, it does not inform on the traits of individual constituent antibody molecules
We present a survey of the various pathologies explored to date using antibody mass spectrometry, highlighting unique insights into the characteristics of the diseasespecific immune repertoire and the therapeutic molecules or strategies which may arise from these studies

Summary

INTRODUCTION

The discovery of a substance in serum with the ability to protect against disease dates back to Emil von Behring and Shibasaburo Kitasato [1]; just a year later, Paul Ehrlich made the first reference to ‘Antikörper’, or antibodies, in an 1891 report [2]. Serological studies of SARS-CoV-2infected patients and analysis of their B cells led to rapid profiling of longitudinal antibody responses to infection [43,44,45,46], contributing to the unprecedented speed of new and effective vaccine development [47] and discovery of neutralizing mAbs [48,49,50,51,52,53] While these data have improved our understanding of protection afforded by serum antibodies, the relative abundance and functionalities of the individual SARS-CoV-2-reactive antibodies circulating in blood have remained unknown. Serum antibodies identified from Ig-Seq and expressed as mAbs bound to NY-ESO-1 with KDs as low as 2.0 nM

ALTERNATIVE METHODS FOR IMMUNOPROTEOMIC ANALYSIS OF DISEASE

Findings

DISCUSSION