Multivalent influenza vaccine using exosomes from probiotic E. coli

Abstract A universal influenza vaccine that protects against all strains of influenza is a high prioritySeasonal influenza epidemics account for andgthospitalizations and andgtdeaths each year in the U Swith more thanof the deaths occurring in the elderlyThe Centers for Disease Control andampPreventionCDCestimate the economic impact of seasonal influenza in the United States ranges from $to $billion and pandemic influenza ranges from $to $billionThe proposed research directly addresses the limitations of both pandemic and seasonal flu vaccinesVersatope licensed a unique technology platform that includes an influenza antigen construct that is potentially effective against several strains of influenza in mouse and ferret animal modelsIt is expressed in Escherichia coli and derived from recombinant outer membrane vesiclesrOMVsthat contains four repeats of diverse sequences from the ectodomain of the genetically conserved ion channel and drug targetMxM e rOMVsThe ferret study showed higher levels of antigen specific antibodies and lower viral loads of a human pandemic H Ninfluenza isolate following prime boost immunization ofxM erOMVs compared to a commercially available influenza vaccineThe rOMV vaccine delivery is innovative because our Ecoli production strain has been genetically engineered to detoxify lipopolysaccharideLPSmore thanfoldand does not require chemical extraction of LPS to detoxify the final productand produces rOMVs more thanfold compared to the parental probiotic strain of BSLbacteriaSince it is known that influenza undergoes antigenic variation under immunologic selectionthe Mectodomain alone may not be a sustainable vaccine candidate for long term preventative applications in humansAlthough our currentxM erOMV vaccine candidate contains diverse influenza sequences from one target antigenwe propose to develop a multi antigen influenza vaccine based on this candidate and to demonstrate improved protection against two different strains of influenzaH Nand H Nin the mouse modelWe expect that our approach using multiantigenconserved domains from representative hemagglutininneuraminidase and nucleoprotein together with Mectodomainsinfluenza construct will yield stable rOMVs and provide protection against multiple influenza strains by focusing the immune response to genetically conserved domains representing influenza antigenic diversityrOMVs are ideally suited for a multi valent vaccine because the recombinant proteins can be expressed as fusion proteins and or independently targeted to the lumenthe membraneor the surface of rOMVsOur proposed research program is primarily translationalthe outcome of which will guide the path toward a viable single dose vaccine for seasonal and pandemic influenzaThe development of this new multivalent influenzarOMV will enable large scale production suitable for non clinical developmenttoxicologyclinical studiesand commercial developmentWe will also identify the minimum dose required for immunogenicity for future safety toxicity studiesThese rOMVs represent a potentially safe and simple subunit vaccine delivery platform that will increase the range of protection against multiple strains of pandemic and seasonal influenza and reduce the overall hospitalization mortality and economic impact Project Narrative Versatope is developing a universal influenza vaccine candidate capable of potentially protecting against all strains of influenza and has already demonstrated a significant improvement over commercial influenza vaccine candidateswith immunity imparted to multiple strainsThe proposed project will continue the high priority work of developing a new multivalent and universal influenza vaccine candidate capable of protection against genetically diverse influenza strains and suitable for large scale commercial production