No commercial vaccine is yet available against Group A Streptococcus (Strep A), major cause of pharyngitis and impetigo, with a high frequency of serious sequelae in LMICs, and an important driver of antibiotic use.
The highly conserved Group A Carbohydrate (GAC), conjugated to an appropriate carrier protein, has been proposed as an attractive vaccine candidate. GAC consists of a polyrhamnose (polyRha) backbone with alternating N-acetylglucosamine (GlcNAc) at the side chain. Both native GAC and the polyRha backbone only have been proposed as vaccine candidates. Here, for the first time, GAC and polyRha conjugates have been compared in different animal models, showing higher anti-GAC IgG responses elicited by GAC with stronger binding capacity to Strep A strains. Moreover, we confirmed that GlcNAc is an important component of the GAC epitope motif and it is recognized by monoclonal antibodies only in the context of the polyRha backbone.
Also, the possibility to use Strep A protein antigens with a dual role of antigen and carrier, to enhance the efficacy of the final vaccine and reduce its complexity, has been explored. All protein antigens resulted good carrier for GAC, however, conjugation to the polysaccharide had a negative impact on the anti-protein functional responses. Therefore, we selected CRM as protein carrier and used a Design of Experiment approach to increase process robustness and conjugation yield.
This work contributes to the development of a vaccine against Strep A and shows how recent advancements in the field of conjugation can lead to improved design of glycoconjugate vaccines.