Especially encouraging was the observation that, although L.inn::vgc strain was injected at a high dose of 10 7 cfu, mice could still efficiently control the infection and showed very low blood levels of pro-inflammatory cytokines thus reducing the detrimental inflammatory responses caused by the wild type Lm. Morphological and histological analysis of spleen after infection with Lm have shown the induction of splenomegaly and granuloma as a result of monocytic infiltrations of the white pulp which were most pronounced on day 3 post-infection while infection with L.inn::vgc only resulted in a splenomegaly without any significant morphological changes detectable (Fig. 3A,3B) . The intensity of the morphological and histological alterations in spleens paralleled the level of Listeria-induced DTH responses, as the in vivo induction of DTH after L.inn::vgc infection was also significantly lower than DTH induction following Lm infection (Fig. 3 and Fig. S1 ). We therefore show that the recombinant L.inn::vgc strain shows a significantly reduced proinflammatory and CD4 + mediated inflammatory response compared to Lm, thereby addressing one major concern regarding the use of live Lm as a vaccine.