Increasing available choices for conjugate vaccine technology by producing carrier proteins in Scarab Genomics' reduced genome E. coli strains

Scarab Genomicsgoal is to commercialize carrier proteins for conjugate vaccine manufactureThis proposal focuses on two bacterial carrier proteins that have been approved by the FDA and that are in use in pre clinical and clinical studiesExoprotein AEPAfrom Pseudomonas aeruginosa and Protein DPDfrom non typeable Haemophilus influenzaeThese proteins are difficult to make by the conventional Ecoli fermentation processes and are in very short and unreliable supply commerciallyEPAor presently unavailablePDScarab s Clean Genome Ecoli fermentation technology has not only enabled continuous flow fermentation for at leastdays to become realitybut has proved to be very efficient at producing the carriers we have testedwith reliable production and good yieldsScarab strains provide much greater safety and productivity than conventional bacterial fermentation strainsConjugate vaccines have been enormously successful in preventing pneumococcal and meningococcal diseasesboth in the developed and the developing worldPfizer s pneumococcal vaccine Prevnarmade USDbillion last yearThere is still a huge unmet demand for pneumococcal vaccines in many parts of the worldestimated by the vaccine alliance Gavi as two billion doses over the next decadeAlthough the carrier protein CRMis used in many pneumococcal vaccinesproblems such as carrier induced epitope suppressionCIEScontributed to the decision by GlaxoSmithKline to use PD as a carrier forof thepneumococcal serotypes targeted in Synflorix$million in sales inInterest in conjugate vaccine research is expanding to other infectious diseasessuch as HIV and malariaand also chronic conditions and addictionsThe need for multiple carrier proteins is driven byiCIESa reduction in immunogenicity of vaccines that use the same carrier proteinparticularly relevant as the desire to combine vaccines and improve coverage increasesiithe need to explore multiple carrier proteins when developing conjugate vaccines against specific antigensiiithe emergence of rare serotypes that require new vaccination with a different carriersThis field of study is clearly relevant to the NIH mission both for research and the commercial availability of carriers for preclinical and clinical studiesas well as the production of approved vaccinesThe Phase I specific aims of this Fast Track proposal will demonstrate that EPA and PD express well in Scarab s Clean Genome strains and that they can be produced in a continuous flow processThis will establish feasibility of commercializationNew Scarab technologies will be tested thatiavoid use of antibiotics in the fermentation process andiienable cleaner and more efficient recovery of the productIn Phase IIfor each carrierthe fermentation system will be fully optimized and a downstream process devisedincluding purification procedurethorough analysis of the product and preparation for sale as research grade reagents