Escheriosome mediated cytosolic delivery of Candida albicans cytosolic proteins induces enhanced cytotoxic T lymphocyte response and protective immunity

Abstract

Protection against intracellular fungal infections, in a manner similar to viral challenges necessitates activation of both humoral and cell mediated immune responses in unison. Most of the presently available antigen delivery vehicles including egg phosphatidyl-choline (egg-PC) liposomes, can evoke mainly humoral immune responses in the immunized animals. Keeping this fact into consideration, we earlier developed Escherichia coli membrane lipid vesicles (escheriosomes) and demonstrated that escheriosomes successfully fuse with the plasma membrane of macrophages ensuing in effective cytoplasmic delivery of entrapped antigen, a pre-requisite for inducing CD8+ T cell response against antigens. In the present study, we report the ability of escheriosomes encapsulated Candida albicans (C. albicans) cytosolic antigens (cAg), to generate protective immunity against systemic C. albicans infection in BALB/c mice. The immunization schedule using escheriosome encapsulated cAg induced strong antigen-specific CD8+ T-cell responses, which were markedly higher than that observed in mice immunized with IFA-antigen emulsion, or antigen encapsulated in egg PC liposomes. Interestingly, immunization with cAg delivered in escheriosomes was also successful in complete elimination of C. albicans infection in Balb/c mice. The study suggests that escheriosomes may function as a novel immunoadjuvants and emerge as an effective tool for generating protective immunity against C. albicans infection.