Group A Streptococcal carbohydrate (GAC)

The Group A Streptococcal carbohydrate (GAC) is the signature cell wall polysaccharide of Streptococcus pyogenes, constituting approximately 40-50% of the total cell wall mass (van Sorge et al., 2014). It is composed of a repeating alpha-1,2- and alpha-1,3-linked L-rhamnose backbone with beta-N-acetylglucosamine (GlcNAc) side chains attached to the rhamnose residues (Fiedler et al., 1984). GAC is essential for the structural integrity of the bacterium and plays a critical role in virulence by protecting the pathogen from host innate immune defenses, such as antimicrobial peptides (van Sorge et al., 2014). In clinical settings, GAC is the primary target for Rapid Antigen Detection Tests (RADT) used to diagnose streptococcal pharyngitis (Post et al., 2002). As a therapeutic target, GAC is a leading candidate for the development of universal vaccines because it is highly conserved across nearly all S. pyogenes serotypes (Sabharwal et al., 2006). However, due to historical concerns that the GlcNAc side chain may trigger autoimmune responses leading to rheumatic heart disease, some modern vaccine strategies utilize modified versions of the carbohydrate that lack the GlcNAc component (Kabanova et al., 2018).

Other names

Group A CarbohydrateLancefield Group A antigenStreptococcus pyogenes cell wall polysaccharideGAS carbohydratePoly-rhamnose N-acetylglucosamine antigen

Vaccine candidates utilize GAC or its derivatives (such as dGlcNAc-GAC) conjugated to carrier proteins to induce high-titer, protective IgG antibodies that facilitate opsonophagocytic killing of Streptococcus pyogenes by host immune cells (Sabharwal et al., 2006; Vaxcyte, 2023).