Serotype independent therapeutic vaccine for Streptococcus pneumoniae

In the era of growing antibiotic resistancelife threatening infections with several bacterial pathogens are cause for major concernApproved vaccines exist only for a handful of bacterial pathogensEven when a vaccine is available invasive bacterial diseases can occur due to lack of serotype coveragepoor vaccine response among vaccinated populationsor because many simply don t get vaccinatedThusinnovative concepts are needed to cope with these challengesThe current proposal is aimed at developing a novel post exposure treatment that is serotype independent and can be applied to a variety of gram positive bacteriaThe approachtermed Infection Site Targeted universal Bridging AntigenISTuBAexploits the ability of species specificbut serotypeindependentphage derived bacterial cell wall binding domainsCBDto target anImmunoBridgean antigen against which most people have antibodiesto the surface of bacteriaThe CBD will redirect the pre existing immunity against ImmunoBridge towards the new invading pathogen leading to clearance of infectionIn this proposal prototype ISTuBAs will be created for Streptococcus pneumoniaethe leading cause of community acquired pneumonia as well other life threatening infectionsIn preliminary studies we have demonstrated that ISTuBAs based on an attenuated staphylococcal enterotoxin B vaccineSTEBVaxas ImmunoBridge and Spneumoniae specific CBDs can direct an Saureus specific antibody response to mediate opsonophagocytosis of Spneumoniae strainsBuilding upon these strong preliminary datain Aimwe will test a wide range of candidate CBDs for binding against a broad panel of pneumococcal serotypes to identify the best CBDsA short list of broadly reactive CBDs with high affinity will be used to create candidate ISTuBAs in Aimusing not only STEBVax but also diphtheria toxoidCRMand Tetanus toxoid as ImmunoBridgeThe candidate ISTuBAs will be thoroughly characterized for biochemical and functional properties including opsonophagocytosis in presence of anti ImmunoBridge antibodiesTwo best ISTuBA candidates will be tested in mouse intranasal model of Spneumoniae infection in AimUpon successful completion of Phase I we anticipate a Phase II project that will focus on optimization of the constructsextensive efficacy testing in both pneumonia and sepsis modelsformulationpharmacokinetics and other IND enabling studies