An Improved Manufacturing Process for a Recombinant Polyprotein Vaccine Combating the devastating global disease of leishmaniasis with a. new therapeutic and prophylactic vaccine

摘要

A new recombinant protein vaccine against leishmaniasis has been produced by fusing portions of three leishmania-derived proteins. To simplify manufacturing, process improvements included removal of a 6-histidine sequence near the amino terminus, and the mutation of a proteoiytic hot spot. The improved manufacturing method consists of fermenting an engineered version of the HMS-174 strain of E. coli following current good manufacturing practice regulations at the 30-L scale. A purification scheme yields purified protein product at greater than 100 mg/L.The purified protein then yields a stable cake that can safely be sent to clinical trials. The product was tested with the adjuvant monophosphoryl lipid A in stable emulsion (MPL-SE) in a murine potency assay. The Leish-110f recombinant protein product reported here is an improved version of the original leishmaniasis vaccine.