Engineering Secretory IgA against Infectious Diseases

Abstract

The dawn of antibody therapy was heralded by the rise of IgG therapeutics. However, other antibody classes are at our disposal—one of the most exciting is IgA and is the most abundant antibody class within humans. Unlike IgG, it is uniquely specialized for mucosal applications due to its ability to form complex Secretory IgA (SIgA) molecules. Since the mucosa is constantly exposed to potential infectious agents, SIgA is pivotal to disease prevention as an important component of the mucosal barrier. Compared to IgG, SIgA has proven superior effectiveness in mucosal surfaces, such as the airway epithelium or the harsh gut environment. Despite this, hurdles associated with low yield and challenging purification have blocked SIgA therapeutic advancement. However, as a result of new antibody engineering strategies, we are approaching the next generation of (IgA-based) antibody therapies. Strategies include fine-tuning SIgA assembly, exploring different production platforms, genetic engineering to improve purification, and glycoengineering of different components. Due to its stability in mucosal environments, SIgA therapeutics would revolutionize passive mucosal immunotherapy—an avenue still underexploited by current therapeutics. This chapter will focus on the current perspectives of SIgA engineering and explore different approaches to unlocking the full therapeutic potential of SIgAs.