Development of a S. Paratyphi A / S. Typhi bivalent vaccine through proof-of-concept (POC) in animals

A bivalent Paratyphi-Typhi vaccine is considered important to control the enteric fever burden. While there are vaccines against S. Typhi, currently there is none against S. Paratyphi. We propose to select a strain (of S. Paratyphi A) from clinical isolates, optimize OSP production & characterization processes, establish an OSP conjugation process with a carrier protein, develop a bivalent formulation with Vi-DT conjugate (already developed at IVI), and perform animal studies to evaluate immunological properties of anti-OSP and anti-Vi induced by the conjugates in monovalent (Para A OSP) and bivalent vaccines with/without adjuvants to confirm the proof-of-concept (POC) in preclinical studies. The project deliverables would be development of scalable, 5-10L scale process for OSP production and 1-2g scale conjugation with a carrier protein, qualification of anti-OSP/Vi responses including antibacterial activity & development of relevant release assays, and evaluation of immunological properties of the bivalent vaccine with adjuvants/ formulation in animal models.