Engineering lactococci and lactobacilli for human health

Food-grade lactic acid bacteria (LAB) are good candidates for the development of oral vectors, and are attractive alternatives to attenuated pathogens, for mucosal delivery strategies. In this review, we summarize recent results on the use of LAB as mucosal delivery vectors for therapeutic proteins and DNA vaccines. Most of this work has been based on the model LAB, Lactococcus lactis, which is suitable for the heterologous expression of therapeutic proteins. Recombinant lactococci and lactobacilli strains expressing antiproteases and antioxidant enzymes have been tested successfully for their prophylactic and therapeutic effects in murine models of colitis. Recombinant lactococci secreting autoantigens have been found to be effective for the treatment of type 1 diabetes. Also, recombinant lactococci delivering DNA were able to prevent a bovine beta-lactoglobulin (BLG)-allergic reaction in mice. We believe that these various coherent findings demonstrate the potential value of using LAB, particularly lactococci and lactobacilli strains, to develop novel vectors for the therapeutic delivery of proteins to mucosa! surfaces. Further tests and in particular human clinical trials are now important next steps to conclude on the benefit of these approaches for human health.