Liposome-displayed peptide vaccine against disseminated candidiasis by clinically-relevant Candida species

PROJECT SUMMARY The goal of this proposal is to develop an anti-Candida peptide vaccine that works alone or as an adjunct to antifungal drugs to reduce fungal burden and morbidity due to life-threatening disseminated candidiasis, which remains the most common bloodstream infection in hospitalized patients in the US. Despite the availability of modern antifungal therapy, crude mortality in the last decade has remained unacceptably high. In particular, C. auris is a multidrug-resistant (MDR), health care-associated fungal pathogen, and has emerged as the first fungal pathogen to cause a global public health threat. There are no effective vaccines for Candida infection or indeed for any fungi, and significant therapeutic challenges remain. Additionally, current anti-Candida treatments are plagued by significant toxicity and poor efficacy, especially treating drug resistant Candida species in immunocompromised patients. Thus, there is a pressing and urgent need for disease prevention through active and passive immunization strategies. We previously identified Fba and Met6 (Fba, derived from fructose- bisphosphate aldolase and Met6, derived from 5-methyltetrahydropteroyltriglutamate homocysteine methyltransferase) peptide immunogens that induce protective antibodies in a mouse model of candidiasis. To further advance this antifungal peptide vaccine toward human clinical application, a novel particle-inducing liposome system containing cobalt-porphyrin-phospholipid (CoPoP) will be used as an ultrapotent vaccine adjuvant platform for Fba and Met6 peptides. In preliminary data, immunization of mice with liposome-displayed Fba / Met6 peptides or two-peptide combination induced robust IgG responses and balanced Th1/Th2 immunity or Th1-baised which would play a key role contributed to resistance to invasive candidiasis.