Prophylactic vaccination with phage-displayed epitope of C-albicans elicits protective immune responses against systemic candidiasis in C57BL/6 mice

Epitope LKVIRK on 47 kDa of heat shock protein (Hsp) 90 of Candida albicans, corresponding to residues 396-391 of the Hsp90, is recognized by patients recovering from invasive candidiasis. The efficacy of hybrid phage displaying epitope LKVIRK in the N-terminal region of the major coat protein (pVIII) in inducing anti-invasive candidiasis immune response was studied in C57BI.J6 mice. Indirect phage-ELISA results demonstrated that the mice immunized with hybrid phage had significantly higher titers of epitope LKVIRK-specific serum IgG as compared to those immunized with heat-killed C albicans (HK-CA). C57BU6 mice immunized either with hybrid phage or with wild-type phage also developed significant levels of delayed-type hypersensitivity (DTH) response and splenocyte proliferation. as well as with HK-CA. In addition, high levels of IFN-gamma in the CD4+ splenocytes from phage-immunized mice were detected as well during I week post-inoculation. Furthermore, mice immunized with hybrid phage acquired a resistance to systemic C. albicans infection as confirmed by fewer C. albicans cells in the kidneys, and had a longer lifespan compared to control groups following intravenous challenge with C. albicans. These results indicate that hybrid phage displaying epitope LKVIRK may serve as a potential vaccine conferring a resistance to systemic candidiasis. (c) 2004 Elsevier Ltd. All rights reserved.