BIOLOGICAL MIMETICS, INC. — Department of Health and Human Services SBIR Phase I: NIAID

Description

AbstractMethicillin resistant Staphylococcus aureusMRSAis one of the leading causes of many life threatening infections such as skin and soft tissue sepsispneumoniaosteomyelitis and endocarditisDue to the growing incidence of multiple drug resistance in Saureus strains and the absence of effective new antibioticstreatment options are becoming increasingly limitedDifficulties in developing new antimicrobials adds to the urgent need for developing a highly protective MRSA vaccineSubunit proteinand polysaccharide based vaccines have failed to trigger strong immune responses in clinical studiesWe propose to assess a whole cell vaccine approach which will contain multiple antigens virulence factors to stimulate a more robust and protective immune responseWe recently developed a novel method to produce gamma radiationinactivated vaccines in the presence of a Mn antioxidantMDPderived from the extremely radiation resistant bacterium Deinococcus radioduransUnder aqueous conditionsMDP protects the surface proteinsepitopesof cells and viruses from oxidative damage at supralethal radiation dosesyielding completely inactivated but highly immunogenic vaccine candidatesApplying this approachwe previously demonstrated that immunization with a gamma radiation inactivated MRSAIr MRSA using USAstrainvaccine candidate conferred protection from MRSA infection of skin wounds using a mouse modelWe propose to extend these studies to evaluate the immunogenic and protective efficacy of a new Ir MRSA vaccine candidate in a mouse model mimicking hospital acquiredHA MRSAinfections that are common surgical complicationsTo ensure a diverse expression of bacterial proteinswe propose to propagate the bacteria under different growth conditions designed to produce planktonic and biofilm formsIn additionwe will determine whether a vaccine made from HAMRSA can stimulate cross protection against challenge with a community acquiredCAMRSA strainSuccessful completion of these proposed studies and those to follow will result in a potential universal MRSA vaccine candidate suitable for human clinical trials Project narrativeWe propose to assess the feasibility of developing a whole cell inactivated methicillinresistant Staphylococcus aureusMRSAvaccine candidate using a novel gammairradiation approachWe have successfully applied this approach to a communityacquired MRSA strain in a skin infection mouse model and aim to extend this approach to hospital acquired infections in a surgical modelThe irradiation method is rapidcosteffective and readily scalable to any infectious pathogenbacterial or viral