Development of a Recombinant Vaccine Against Streptococcus Pyogenes Infection and Disease

A vaccine to protect against diseases resulting from infection with Streptococcus pyogenes is under development. This vaccine utilizes a recombinant fusion protein (SpeAB) comprising of genetically detoxified SpeA, a secreted toxin, and SpeB, a surface bound and secreted cysteine protease. During phase I investigations a lead vaccine formulation was determined by optimization of critical parameters such as buffer, pH, stabilizer, and adjuvant interactions. Potency studies in mice demonstrated significantly greater induction of an antigen-specific IgG immune response to the vaccine than antigen alone. Additionally, the antibodies produced were functional at neutralization of wild type SpeA toxin. These results demonstrate that the SpeAB vaccine developed during the phase I investigation has great potential to provide protection against diseases resulting from infection by Streptococcus pyogenes. For phase II development of the vaccine the overall goal is to complete non-clinical safety studies in preparation of movement into clinical trials. To achieve this goal technical objectives including optimization of assays for antigen characterization, stability, and potency, development of cGMP scalable processes for fermentation and purification of SpeAB, and correlation of SpeAB potency with formulation stability will be investigated.