Generation and evaluation of A2-expressing Lactococcus lactis live vaccines against Leishmania donovani in BALB/c mice.

Leishmaniasis is a parasitic disease affecting over 12 million individuals worldwide. As current treatments are insufficient, the development of an effective vaccine is a priority. This study generated and assessed the efficacy of Leishmania vaccines engineered from the non-colonizing, non-pathogenic Gram-positive bacterium Lactococcus lactis. A truncated, codon-optimized version of the A2 antigen from Leishmania donovani was engineered for expression in Lactococcus lactis in three different subcellular compartments: in the cytoplasm, secreted outside the cell or anchored to the cell wall. These three A2-expressing Lactococcus lactis strains were tested for their ability to generate A2-specific immune responses and as live vaccines against visceral Leishmania donovani infection in BALB/c mice. Subcutaneous immunization with live Lactococcus lactis expressing A2 anchored to the cell wall effectively induced high levels of antigen-specific serum antibodies. It was demonstrated that Lactococcus lactis-based vaccines are a feasible approach in the generation of live vaccines against leishmaniasis. The Lactococcus lactis strains generated in this study provide an excellent foundation for further studies on live bacterial vaccines against leishmaniasis and other pathogens.

Mycobacteria in Crohn's disease: how innate immune deficiency may result in chronic inflammation.

Crohn's disease (CD) is often considered to be an autoimmune condition or, alternatively, an autoinflammatory condition, based on the observation of host-directed inflammatory processes. However, the underlying basis of this deleterious inflammatory response remains elusive. Recent findings from genetic and genomic studies have altered the perspective on the pathogenesis of CD, hinting at defects in innate immune sensing of intracellular bacteria and the handling of these organisms through autophagy. These findings are consistent with emerging data from immunological studies that point to a systemic immune deficiency in CD patients. Both sets of data (genetic predisposition and immunodeficiency) are consistent with the longstanding hypothesis that mycobacteria might be involved in the etiology of CD. In this article, we discuss the convergence of these three lines of investigation and highlight important knowledge gaps required in order to address the mycobacterial hypothesis with greater clarity. In the coming years, clinical immunological investigations should focus on defining the specificity of functional immune defects with regards to microbes and their associated ligands. Should CD result from a dysfunctional host-pathogen interaction, elucidation of the microbes that can exploit such defects to induce a chronic inflammatory disease is critical for the development of subsequent diagnostic assays and clinical interventions.