Double Chimeric Peptide Vaccine Feasible for Human Use that Protects against Disseminated Candidiasis caused by medically important Candida species

PROJECT ABSTRACT The goal of this Phase I STTR proposal is to develop and establish preclinical proof of concept for the first double chimeric peptide vaccine feasible for human use that protects against disseminated candidiasisDisseminated candidiasis is the third leading cause of nosocomial bloodstream infections in the USwithcases per year and associated healthcare costs of $billionanddespite the availability of antifungal therapyat leastof affected individuals die of the diseaseThe infection is caused by multiple species of fungal genus Candida with Candida albicans being the most commonIn additionimmunocompromising conditions increase susceptibility to the diseaseNeutropenia is one of the most common risk factors for the development of disseminated candidiasis in humansin which the mortality is greater thandespite antifungal therapySince there is no approved antifungal vaccine for use in humans and current treatments have limited efficacythe development of novel methods of disease prevention and treatment such as active and passive immunization strategies are critically importantVaccination of high risk groups is a particularly promising strategy to prevent invasive Candida infectionAn ideal vaccine candidate wouldtarget multiple antigenic epitopes to achieve the greatest efficacy andbe composed of epitopes that are homologous among medically relevant species of Candida such that universal protection against Candida infection could be achieved rather than against a single species such as CalbicansUnder development currentlythere is only one vaccine formulation against Candida albicansNDVNovaDigm Therapeuticswhich has completed Phase I clinical trialsThe single antigen vaccine may prove to provide protection in some cases of disseminated candidiasishoweverit may have limited efficacy in protecting against Calbicans and other medically relevant non albicans Candida speciesincluding the emerging multi drug resistant CaurisThis proposal seeks to further the development of a novel double chimeric peptide vaccine that has shown promising results in animal models of disseminated candidiasisThe vaccine is composed of two antigens present in Calbicans as well as other medically relevant species of CandidaThe existing vaccine will behumanizedby conjugating it to a human approved carrier such as tetanus toxoid and tested in animal models of disseminated candidiasis caused by multiple species of CandidaIn additionsince neutropenia is a significant risk factor for development of disseminated candidiasisthehumanizedvaccine will be tested for its ability to protect hosts against the disease if an immunocompromising event occurs post vaccinationThe results of the proposed studies will provide non clinical proof of concept for our strategy and will support further development of our double chimeric peptide vaccine PROJECT NARRATIVE The goal of this Phase I STTR proposal is to develop and establish preclinical proof of concept for the first double chimeric peptide vaccine feasible for human use that protects against disseminated candidiasis caused by medically important Candida speciesDisseminated candidiasis is the leading cause of nosocomial bloodstream infections in the USwithcases per year and associated healthcare costs of $billionanddespite the availability of antifungal therapyat leastof affected individuals die of the diseaseThe demonstration of preclinical efficacy of thehumanizedvaccine in this proposal will provide compelling data to seek Phase II STTR funding and advance this program into the clinic