DEVELOPING A SCALABLE MANUFACTURING PROCESS FOR AN ORAL BACTERIOPHAGE PRODUCT THAT PREVENTS CHOLERA

PROJECT SUMMARYCholera is an acute and severe disease caused by the bacterium Vibrio cholerae that is spread primarilythrough contaminated water sources due to a lack of adequate sanitation infrastructure. The World HealthOrganization estimates that there are at least 3 million cases globally per year, 40 percent of which are spreadthrough household transmission. Current prevention methods require significant investment of resources andtime for efficacy, but household contacts of cholera patients often present with cholera symptoms two to threedays after the initial patient becomes sick. In addition, the preventive use of antibiotics is not recommendeddue to widespread resistance and the known negative consequences of dysbiosis. There is a pressing need todevelop a targeted clinical intervention to prevent the community spread of cholera using a rapid prophylactictreatment. The goal of the proposed studies is to demonstrate feasibility of developing our phage-based clinicalintervention, ProphaLytic-VC, to prevent the community spread of cholera. ProphaLytic-VC is an orallyadministered cocktail of three different phages known as ICP1, ICP2, and ICP3. To date, these are the onlythree virulent phages found in association with epidemic strains of cholera. Detailed genomic and phenotypiccharacterization each of the phages has been conducted by the academic partner, resulting in genomesequences, annotation, and identification of the host receptors. The combination of the three has beenevaluated to demonstrate potency in reducing colonization of V. cholerae and prevention of cholera symptomsin two animal models of V. cholerae colonization and pathogenesis. Here, we propose studies to optimize arobust and scalable manufacturing process for ProphaLytic-VC, as there is currently little manufacturingexperience in the USA due to the novel nature of the product. We will construct two phage production strains,develop a scalable phage production and purification scheme, and evaluate any potential local of systemictoxicity. At the successful conclusion of Phase I, we will have a resultant Master Phage Stock (MPS) ofProphaLytic-VC from an optimized large-scale production scheme that is potent against V. cholerae and safewith repeated oral administration. STTR Phase II funding will be used to fund further activities to generate aworking phage seed stock from the MPS to proceed with a Phase I clinical trial.