In this study, we define a unique vaccine strategy which is based on a rationally designed pathogen by complementation of a non- pathogenic strain with selected genes necessary to induce a vigorous immune response. To illustrate the proof of principle of this strategy we used the Listeria model by taking a non-pathogenic L.inn strain and complementing it with genes from pathogenic Lm which were previously shown to be a sine qua non requirement for intracellular growth and survival [18] . This novel vaccine strategy resulted in generation of a recombinant strain (L.inn::vgc) that possesses properties needed to induce the marked protective immunogenic properties of the wild type Lm but is attenuated in virulence as well as in its capacity to induce host detrimental cellmediated inflammation. The recombinant L.inn::vgc strain showed a significant in vivo survival rate in the first 3 days post-infection (Fig. 1A) . This observation is in accordance with our recent finding that the L.inn::vgc strain is able to survive in phagocytic host cells [18] . Moreover, it has the capability to induce identical Type I interferon at levels similar to wild type Lm. As previously shown by McAffrey et al., 2003, induction of type 1 IFN is a surrogate marker indicating access of Listeria into the cytosol of antigen presenting cells [17] . We have shown that the L.inn::vgc strain could use the complemented virulence factors to escape into the cytosol and subsequently be presented to CD8 T lymphocytes. In this context Zwaferink et al. 2008 have shown a role for IFNb in macrophage cell death. Treatment of macrophages with this cytokine could enhance host-cell membrane permeabilization by listeriolysin consequently leading to cell apoptosis [27] .