Development of a Recombinant Vaccine Against Streptococcus Pyogenes Infection and Disease

In this phase I proposal we propose development studies for a vaccine targeting diseases caused by infection with Streptococcus pyogenes. This vaccine utilizes a recombinant fusion protein comprising of SpeA, a secreted toxin, and SpeB, a surface bound and secreted cysteine protease. Combination of these two virulence factors provides protection against most strains of the bacteria. This antigen has demonstrated promise in proof of concept potency studies in which mice were protected from toxic shock as well as infection following challenge. The overall goal is to produce a lead formulation for the SpeAB vaccine, optimized for safety, potency, and stability, which can be rapidly advanced through non-clinical safety studies and into phase I clinical trials. To achieve this goal we utilize a rational, systematic approach to formulation development allowing rapid identification of a robust formulation. The biophysical characteristics of SpeAB and how environmental factors such as pH, ionic strength, and temperature impact the antigen will be determined. Interactions with aluminum adjuvant systems will also be investigated to develop a robust vaccine formulation. Successful commercialization of this vaccine will reduce morbidity and mortality rates, as well as medical care costs, associated with S.pyogenes infection in both military and civilian populations.