Serology in the 21st century: the molecular-level analysis of the serum antibody repertoire

• New technologies have revolutionized serological antibody analysis.
• NextGen sequencing and shotgun proteomics help identify and quantify serum mAb's.
• Clonality and dynamics of serum mAb repertoire in various states can be addressed.
• New tools available for identifying novel antigens that elicit serological response.

The ensemble of antibodies found in serum and secretions represents the key adaptive component of B-cell mediated humoral immunity. The antibody repertoire is shaped by the historical record of exposure to exogenous factors such as pathogens and vaccines, as well as by endogenous host-intrinsic factors such as genetics, self-antigens, and age. Thanks to very recent technology advancements it is now becoming possible to identify and quantify the individual antibodies comprising the serological repertoire. In parallel, the advent of high throughput methods for antigen and immunosignature discovery opens up unprecedented opportunities to transform our understanding of numerous key questions in adaptive humoral immunity, including the nature and dynamics of serological memory, the role of polyspecific antibodies in health and disease and how protective responses to infections or vaccine challenge arise. Additionally, these technologies also hold great promise for therapeutic antibody and biomarker discovery in a variety of settings.