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Obligatory intracellular parasites such as Plasmodium sp, Trypanosoma cruzi, Toxoplasma gondii and Leishmania sp are responsible for the infection of hundreds of millions of individuals every year. Since first reported in 1987, it is now well established that CD8 T cells are important factors in host immune protection against these parasites. Obligatory intracellular stages of these parasites can deliver antigens to the host cell cytoplasm that are presented through MHC class I molecules to classic CD8 cytotoxic T cells. The in vivo priming conditions of specific CD8 T cells during natural infection are largely unknown and remain as an area that has been poorly explored. The antiparasitic mechanisms mediated by CD8 T cells have been partially elucidated and include both interferon-γ-dependent and –independent pathways. The fact that CD8 T cells are potent inhibitors of parasitic development prompted many investigators to explore whether induction of these T cells can be a feasible strategy for the development of effective subunit vaccines against these parasitic diseases. Studies performed on experimental models supported the hypothesis that CD8 T cells induced by recombinant viral vectors or DNA vaccines could serve as the basis for human vaccination. They also revealed that regimes of immunization consisting of two different vectors (heterologous prime-boost) are much more efficient in terms of expansion of protective CD8 T lymphocytes than immunization with a single vector. The results obtained using experimental models have led to clinical vaccination trials that are currently underway.