Multivalent influenza vaccine using recombinant outer membrane vesicles

Abstract A universal influenza vaccine that protects against all strains of influenza is a high priorityThe 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 has developed a unique influenza M e 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 vesiclesrOMVsor M e rOMVsThe ferret study showed higher levels of antigenspecific antibodies and lower viral loads of pandemic H Ninfluenza following prime boost administration of M e rOMVs compared to a commercially available influenza vaccineThe OMV vaccine delivery is innovative because our Ecoli production strain has been genetically engineered to detoxify lipopolysaccharideLPSmore thanfoldthey do not require chemical extraction of LPS to detoxify the final productand to increase OMV formation more thanfold compared to the parental probiotic strain of BSLbacteriaSince it is known that influenza undergoes antigenic variation under immunologic selectionthe Mectodomain may not be a sustainable vaccine candidate for long term preventative applications in humansAlthough our current M e rOMV vaccine candidate contains diverse strain sequences from one target antigenwe propose to develop a multi antigen influenza vaccine candidate and to demonstrate improved protection against heterologous challenge using the multivalent influenza rOMV compared to the M e rOMV in the mouse modelWe expect that our approach using multi antigenconserved domains from representative hemagglutininneuraminidase and nucleoprotein together with Mectodomainsinfluenza construct will yield stable rOMVs and provide with protection against multiple influenza strainsOMVs are ideally suited for a multivalent vaccine because recombinant proteins can be expressed as fusion proteins and or independently targeted to the lumenthe membraneor the surface of OMVsOur proposed research program is primarily translationalthe outcome of which will guide the path toward a viable single dose vaccine for pandemic influenza AThe development of this new multivalent influenza rOMV will enable large scale production suitable for non clinical development and toxicologyclinical 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 economic impact Project Narrative Versatope is developing a universal influenza vaccine candidate capable of 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 capable of protection against multiple strains of pandemic influenza and suitable for large scale commercial production