F2F Poster 21st Lancefield International Symposium for Streptococci and Streptococcal Diseases 2022

Recombinant glycoconjugate vaccine production platform to combatĀ Group A, C and G streptococcal infections (#146)

Sowmya Ajay Castro 1 , Keira Burns 2 , Ian Passmore 3 , Sarah J Thomson 1 , Mark Reglinski 1 , Fatme Mawas 2 , Alexandra Shaw 2 , Brendan W Wren 3 , Helge C Dorfmueller 1
  1. University of Dundee, Dundee, ANGUS, United Kingdom
  2. The National Institute of Biological Standards and Control , (NIBSC), London, United Kingdom
  3. Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom

Streptococcus pyogenes (Group A Streptococcus, GAS), S. dysgalactiae and S. dysgalactiae subsp. equisimilis (Group C and G Streptococci) are closely related human pathogens. They share many virulence factors, cause very similar types of disease, and produce each an immunogenic group-specific surface carbohydrate.

GAS cause the highest mortality of these three Lancefield groups, with annually more than 500,000 patients dying worldwide, mainly caused by auto-immune post-infectious diseases. To avert long-term disability and death, and reduce the disease burden on mankind, the WHO has made it a global priority to develop the first GAS vaccines. One major challenge is the identification of components that are conserved and subsequently protect humans from all >250 GAS serotypes.

The Group A Carbohydrate is an essential component of GAS, found in all serotypes, and its polyrhamnose backbone is a validated vaccine candidate. Likewise, the Group C and G carbohydrates are essential for the bacteria. These abundant, conserved and surface-exposed cell wall carbohydrates provide exciting new opportunities to be exploited for vaccine development, analogous to the global efforts on building the first Group A Carbohydrate vaccine candidates.

We will present our novel platform technology facilitating the development of the first recombinantly produced carbohydrate-based vaccine candidates for Group A, C and G Streptococci. We will present our findings from our proof-of-principle study producing E. coli Outer Membrane Vesicles decorated with the GAS carbohydrate backbone and explain how we have combined synthetic biology and glycoengineering to develop the first recombinant Group A, C and G glycoconjugate vaccine candidates. Our latest data, including immunisation studies, will be presented.