Group A Streptococcus (GAS) is a major human pathogen responsible for over half a million deaths annually. Serious invasive infections and chronic autoimmune sequelae, triggered by untreated superficial infections, are the primary causes of its extensive morbidity and mortality. Despite the urgent need, a vaccine against GAS is not yet available but remains a global health priority.
The pilus of GAS, a long, hair-like fibre protruding from the cell surface, plays a crucial role in the earliest stages of colonization and infection by mediating host cell adherence and biofilm formation. Evidence suggests that immunity to the pilus can be protective, but addressing antigenic variation poses a significant challenge.
We have investigated multiple approaches to vaccine development, including 1) expressing GAS pili from different variants in the food-grade bacterium Lactococcus lactis to use as a live mucosal vaccine and 2) using structural modelling to design a multivalent domain fusion protein of the main protein component of the pilus, the T-antigen. Both approaches have generated antibody responses in mice that can be neutralising or opsonophagocytic to multiple GAS strains. Protective efficacy has also been observed against nasopharyngeal colonization and invasive disease in mice. Improving efficacy and coverage has been the focus in recent years and here, we provide an update on our progress.
Our results point towards the GAS pilus being an attractive vaccine target and demonstrate that multiple approaches can be used to address antigenic variation.