Ponente
Descripción
Liposomes meet many of the requirements of an ideal adjuvant. However, the release of antigens (Ag) by these vesicles into the cytosol of the Ag presenting cells is limited and the Ag-specific CD8+ cytotoxic lymphocyte (CTL) response exhibit a low efficacy. Previously, our group demonstrated that Sticholysin II (StII), a pore-forming protein from the anemone Stichodactyla helianthus, coencapsulated with the model antigen ovalbumin (OVA) into liposomes (Lp), was able to induce an robust response of INFγ-producing CD8+ T cells with memory capacity and an antitumor activity (1). Lp are usually heterogeneous systems with physical and chemical stability problems. In this sense, New (1994) reported the use of sucrose to prevent liposomal aggregation and avoid the leakage of the encapsulated material (2). For the sake to validate this novel platform (Lp/StII) using tumorals Ag, our group characterized formulations coencapsulating StII and the extracellular domain of Epidermal Growth Factor Receptor (Her1-ECD). The main of this work is to evaluate the effect of sucrose addition to Lp/StII/Her1 on the physico-chemical characteristics of vesicles and the CTL response induced by these formulations containing or not sucrose. Lp/StII/Her1-ECD with sucrose increased the encapsulation efficacy of the Ag and reduced the size of vesicles in the order of 130 nm what increases the probabilities for these liposomes to be caught by dendritic cells (DC) resulting in a better CD8+ cytotoxic response. Animals immunized with Lp/StII/Her1 shown a prominent population of Her1-ECD-specific CD4+ T cells consistent with high antibody titers. Lp/StII/Her1 with sucrose induced a discrete INFγ-producing CTL response, at least under these experimental conditions. This supports the idea that the smaller size particles favor its capture by DC and, in turn, the Her1-ECD Ag cross-presentation to CD8+ T cells.
