Clinical development of the DB Fusion, a serotype-independent vaccine to prevent Shigella dysentery.

We are partnering with Oklahoma State University to develop a paradigm-changing, broadly protective subunit vaccine to prevent the short- and long-term debilitating effects of shigellosis in children living in endemic countries. Unlike all other current Shigella vaccine candidates, which rely on lipopolysaccharide-based, serotype-specific immunity, our approach targets the surface-exposed IpaD and IpaB proteins of the highly conserved Shigella Type III Secretion System (T3SS). This approach obvi ates the complications of combining multiple, diverse serotypes to broaden coverage across Shigella species. The Ipa proteins-based vaccine is intended for intradermal delivery in a novel combination with an adjuvant to promote mucosal and systemic immunity. Intradermal immunization is dose-sparing and may also bypass the poor immunological responses to oral vaccination often observed among children in low-resource settings. We have developed a scheme for expression and purification of a stable recombinant IpaDB fusion protein (DB Fusion), selected an adjuvant for co-delivery with the vaccine, and completed proof-of-concept studies in animals demonstrating cross-species protection. We propose conducting translational Phase 1 and 2/2b studies to evaluate the clinical safety and efficacy of the DB Fusion and advance its candidacy as a Shigella vaccine for pediatric use in endemic areas.