Induction of CD8+ T cell responses against pathogens and cancers is an important goal of modern immunology. Notably, increased ratios of effector/central memory T cells (Tef)/(Tcm) have been described for highly efficacious vaccines. One current approach of translational interest is the use of liposomes encapsulating pore-forming proteins (PFP), such as Listeriolysin O (LLO), which are very effective at priming strong and sustained CD8+ T cell responses. We have been recently shown that Sticholysin II (StII), a PFP from the sea anemone Stichodactyla helianthus, stimulated CD8+ T cells against antigens co-encapsulated into liposomes composed of dipalmitoylphosphatidyl choline and cholesterol (DPPC:Chol). In this work, we demonstrated for the first time that StII shows similar abilities to LLO to induce activation and cross-presentation of OVA in dendritic cells. Remarkably, using an ex vivo ELISPOT assay to monitor INF-γ producing T CD8+ cells with similar properties to Tef, liposomal formulations containing the PFPs induced a strong response of T CD8+ cells specific for OVA-MHC-I. On the other hand, liposomal formulations with equal molar quantities of both PFPs induced comparable frequencies of Tcm-like proliferating INF-γ producing cells to those observed in mice immunized with PFP-free OVA/liposomes. However, mice immunized with liposomes with a different DPPC:Chol molar ratio and containing a higher amount of StII induced increased levels of Tcm-like responses. These results point to the capacity of StII/liposomes to induce T CD8+ responses with properties of both Tef and Tcm supporting their use for the rational design of T cell vaccines against pathogens and cancers.