Title
Authors
Abstract
Cytosolic delivery strategies of antigens to antigen-presenting cells in order to improve the antigen-specific cytotoxic T lymphocyte (CTL) response are currently crucial in the development of anti-tumor and anti-intracellular infections vaccines. Promising strategies have employed the co-encapsulation into liposomes (LP) of bacterial pore-forming toxins (b-PFT) with antigens. Sticholysins (Sts) I and II are pore-forming isotoxins produced by the sea anemone Stichodactyla helianthus. Due to the functional homology of Sts with b-PFT, we studied the antigen-specific CTL-mediated immune response induced by LP co-encapsulating Sts with ovalbumin (OVA) as model antigen. Liposomes encapsulating OVA in the presence (LP/OVA+St) or not (LP/OVA) of Sts were used. Immunization of C57BL/6 mice with LP/OVA+St induced a remarkable CD8+ T-cell expansion and it enhanced significantly an OVA-specific CTL activity, in comparison with LP/OVA treatment. The CTL functionality was assessed using an OVA-expressing murine tumor model and in this scenario LP/OVA+St conferred a higher protection than LP/OVA. Besides, the CTL activity induced by LP/OVA+St was independent of CD4+ T-cells, while anti-tumor response was affected with depletion of the CD8+ T-cells. Interestingly, the inclusion into LP of a StI mutant forming a reversible-inactive dimmer stabilized by a disulphide bond also induced a similar antigen-specific CTL response, indicating the effectiveness of this safer alternative. Our results suggest the potentialities of Sts encapsulated into LP as a novel and promising antigen-cytosolic delivery system for priming CTL-mediated immune responses, which are keys in the immunity against infections and tumors.
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