Protection Against Systemic Candidasis Mediated By Phage-displayed Specific Epitope Of Candida Albicans Heat Shock Protein 90

Fungal infection can be divided into two broad categories superficial and systemic infection. The most common species causing clinical infection is Candida albicans (C. albicans). Superficial infection such as cutaneous and mucocutaneous candida infections caused by C. albicans are relatively common, however, morbidity and mortality of systemic candidal infection has increased significantly over the past two decades.It has been reported the increasing in the proportion of disseminated candidiasis is directly associated with following causes: intravascular catheters, use of broad-spectrum antibiotics, surgical procedures, prolonged ICU stay, and immunocompromising conditions of host, etc. Although anti-fungal drugs such as amphotericin B and azoles have been beneficial in prevention and treatment of candidiasis, non-albicans species with higher resistance rates to anti-fungal drugs, such as C. krusei, C. glabrata, C. tropicalis and C. lusitaniae, have appeared rapidly. These problems therefore led us to develop vaccines with minimal side effect so that they can safely be given to patients with risk of systemic candidiasis before the disease occurs.Previous finding in our lab revealed that hybrid phage particles expressing Candida albicans heat shock protein 90 (SE-CA-HSP90) induced the specific antibody response against SE-CA-HSP90, enhanced delayed-type hypersensitivity (DTH) response, natural killer (NK) activity and concanavalin A (ConA)-induced splenocyte proliferation. Protection of hybrid phage SE-CA-HSP90 against systemic candidiasis in C57BL/6J mice were further evaluated in this paper. Briefly, mice immunized with hybrid phage, wild-type phage and TE-injected were infected with live C. albicans cells intravenously by the lateral tail vein 1 week following the last immunization. Protection was assessed by monitoring survival for 15 days and culturing the kidneys of immunized mice, and the results showed that hybrid phage-immunized mice had fewer colony forming unites (CFU) in the kidneys compared with wild type-immunized mice and TE-injected mice and had a statistically significant survival advantage over TE-injected group. In short, this study has demonstrated that hybrid phage SE-CA-HSP90 mediated the protection systemic candidiasis in C57BL/6J mice, and our results suggest that hybrid phage presenting SE-CA-HSP90 can serve as a vaccine for systemic candidiasis.