Group A streptococcus (GAS) is a common pathogen usually causing mild pathology. However, it can also cause severe invasive disease and result in autoimmune complications, including rheumatic fever and rheumatic heart disease. Australia’s Indigenous populations suffer high rates of these diseases and globally it is estimated that over 500,000 people die each year as a result of either infection or post streptococcal sequelae.
Two major impediments to vaccine development are the large degree of antigenic diversity amongst different GAS isolates and the potential for any vaccine to cause autoimmune pathology. For these reasons, it is essential to define conserved protective epitopes and to include in a vaccine only the minimal amount of GAS antigen required for protection.
We describe that a 12-mer synthetic peptide from the highly conserved carboxylyteminal region of the M protein of GAS conjugated to diphtheria toxoid and adjuvanted with Alum can protect mice from multiple strains of GAS delivered systemically, intranasally or via a skin challenge. Immunity is dependent on memory B cells and T cells, as well as neutrophils and macrophages. Although memory B cells are critical for protection, our data show that existing serum antibodies at the time of challenge are not critical; rather it appears that the ability to respond rapidly to GAS exposure with an antibody response is sufficient. When tested for general toxicology in rabbits and in a rat model of rheumatic heart disease the vaccine was shown to be completely safe with no evidence of heart damage or other immune pathology. The vaccine has now been prepared for a placebo-controlled double blind human Phase I trial that is expected to take place in early 2013.