As mentioned above, the use of LAB and more particularly L. lactis as delivery vehicle was initially focused on the development of mucosal vaccines. Since then, many studies have reported engineered L. lactis strains as live mucosal vaccines for a large number of antigens derived from bacteria, viruses, and parasites [for review see (Bermudez-Humaran & Langella, 2004; Bermudez-Humaran, 2009)]. In this context, Cauchard et al. (2011) recently engineered a L. lactis strain secreting the virulence-associated protein A (VapA) from Rhodococcus equi (a Gram-positive bacterium that causes severe pneumonia in foals) and tested the immunogenic potential of the resulting strain in mice in combination with a recombinant strain of L. lactis secreting biologically active leptin (a pleiotropic hormone with significant immunomodulatory properties) (Bermudez-Humaran et al., 2007). Mucosal administration (either intranasal or oral) of these recombinant strains led to a VapA-specific mucosal immune response and resulted in a significant reduction in R. equi viable counts in liver and spleen after a challenge with a virulent strain of R. equi. In 2011, Marelli et al. (2011) described the construction of recombinant L. lactis strains able to produce the rotavirus spike-protein subunit VP8 in cytoplasmic, secreted, and cell wall–anchored forms. Evaluation of the immune response evoked after mucosal immunization in mice shows that animals orally immunized with the L. lactis strain producing the cytoplasmic form of VP8 developed significant levels of intestinal IgA antibodies, while animals receiving L. lactis producing the cell wall–anchored VP8 form exhibited anti-VP8 antibodies at both local (i.e. intestinal) and systemic (i.e. serum) levels. Strikingly, specific VP8 antibodies evoked by L. lactis strains producing either the cytoplasmic (local antibodies) or the cell wall–anchored (serum antibodies) form of VP8 were able to block rotavirus infection by 50% and 100%, respectively. Later, Saez et al. (2012) developed a mucosal vaccine to control brucellosis based on recombinant L. lactis secreting Brucella abortus Cu-Zn superoxide dismutase (SOD). Mice immunized with this recombinant strain developed SOD-specific IgM antibodies together with SOD-specific sIgA in nasal and bronchoalveolar lavages (BAL). In addition, vaccinated animals were also protected against challenge with a virulent B. abortus strain. Furthermore, the immune response evoked in mice after immunization was improved when the L. lactis strain secreting SOD was co-administered with a L. lactis strain secreting biologically active IL-12 (Bermudez-Humaran et al., 2003). Finally, in one of the most complete works performed in the last years using L. lactis as a live vaccine, Cousineau and coworkers demonstrate the interest in the use of L. lactis as a live vector against the Leishmaniasis, a parasitic disease affecting more than 12 million individuals worldwide (Kedzierski et al., 2006). They first expressed a modified version of A2 antigen from Leishmania donovani in L. lactis in three different cellular locations: cytoplasmic, secreted, or cell wall–anchored forms and tested for their ability to generate A2-specific immune responses and as live vaccines against L. donovani infection in mice (Yam et al., 2011). Subcutaneous immunization with L. lactis expressing the cell wall–anchored form of A2 induced the higher levels of antigen-specific serum antibodies, while mice immunized with L. lactis producing the cytoplasmic form of A2 demonstrated the highest reduction in liver parasitemia after visceral L. donovani challenge. Later, the same group reported the construction of different lactococci strains expressing one of the best-studied Leishmania major antigens, the Leishmania homologue of activated C kinase (LACK), in the cytoplasmic, secreted, or cell wall–anchored forms, and a strain secreting biologically active mouse IL-12 (Hugentobler et al., 2012a, b). Subcutaneous co-immunization with live L. lactis strains expressing the cell wall–anchored form of LACK and secreting IL-12 significantly delayed footpad swelling in L. major-infected mice. Furthermore, immunization with these two strains induced antigen-specific multifunctional TH1 CD4+ and CD8+ T cells and a systemic LACK-specific TH1 immune response. This same group then evaluated the effect against L. major infection in mice after oral immunization with recombinant L. lactis strains deficient in alanine racemase (alr-), an enzyme that participates in cell wall synthesis (Grangette et al., 2004), expressing LACK antigen in the cytoplasmic, secreted, or cell wall–anchored forms alone or in combination with a L. lactis strain secreting mouse IL-12 (Hugentobler et al., 2012a, b). They showed that oral immunization using live lactococci secreting both LACK and IL-12 was the only treatment that partially protected the mice against subsequent L. major challenge. Most importantly, protected animals displayed a delay in footpad swelling, which correlated with a significant reduction in parasite burden. These results demonstrate the potential of L. lactis as a live mucosal vaccine against L. major infection and provide the basis for the development of an inexpensive strategy to combat Leishmaniasis.