Decoding autoimmunity during acute rheumatic fever in First Nations Australians for safe Strep A vaccines.

In 1 out of 2000 people, an infection with the bacteria Streptococcus pyogenes (Strep A) can lead to acute rheumatic fever (ARF), an autoimmune disease that affects the heart. ARF often progresses to rheumatic heart disease (RHD) in over 60% of cases, impacting more than 33 million people worldwide, and disproportionately affecting First Nations people. The exact cause of ARF is still unclear. It is believed that the immune responses to Strep A infection mistakenly attacks similar looking molecules in the body by mistake (termed “molecular mimicry”), although this theory is still debated. Understanding the cause of ARF is crucial for developing a Strep A vaccine, as an unsafe vaccine from the late 1960s inadvertently caused ARF, the disease it was meant to prevent. This project aims to solve this long-standing mystery using innovative single-cell techniques to study both autoimmune and Strep A responses. It will involve studying B and T cells from children with ARF using techniques that include flow cytometry and single cell sequencing to determine whether the same cells can recognize both Strep A and human molecules. This could confirm the theory of molecular mimicry in ARF and suggest that some vaccine components might be unsafe. If we do not find molecular mimicry, our research will provide urgently needed knowledge on the safety of vaccine components and the origins of autoimmunity in ARF. Ultimately, only a vaccine can achieve a lasting reduction in deaths from RHD, especially among First Nations people. This research represents a critical step forward in understanding and combating this complex disease.