SBIR-STTR Award

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.

Keywords:
Spea, Speb, Fusion Protein, Subunit Vaccine Formulation

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.

Keywords:
Streptococcus pyogenes, vaccine, formulation development, safety