A platform for the recombinant production of Group A Streptococcus glycoconjugate vaccines

Strep A are human-exclusive bacterial pathogens killing annually more than 500,000 patients, and no current licensed vaccine exists. Strep A bacteria are highly diverse, but all produce an essential, abundant, and conserved main surface carbohydrate, the Group A Carbohydrate (GAC). GAC contains a rhamnose polysaccharide (RhaPS) backbone, which is a validated universal vaccine candidate. RhaPS vaccine candidate production is currently limited to chemical routes. We engineered the GAC synthesis route to enable the industry standard recombinant production route to couple RhaPS to selected carrier proteins. The integrity of the correct chemical structure of the glycoconjugate vaccines was confirmed by NMR spectroscopy and mass spectrometry. Purified IdeS-RhaPS and NanA-RhaPS produce carbohydrate specific antibodies in mice and rabbits confirming the recombinantly produced RhaPS glycoconjugates as valuable vaccine candidates. We provide a promising route to the production of tailor-made low-cost glycoconjugate vaccines against Strep A and other bacterial pathogens.