Genetically modified lactobacilli as mucosal delivery vectors

Abstract

Mucosal delivered vaccines could offer unquestionable advantages over traditional systemic vaccines. However, in order to design oral vaccines, a delivery system is needed to avoid the degradation of antigens in the stomach and to skew the immune response towards an adaptive immune response rather than the induction of oral tolerance. Lactic Acid Bacteria have been broadly used in the production of fermented foods and beverages (cheese, yogurt, wine...) and have been consumed in large amounts for thousand of years without causing health problems. Notable among them, is the group of mesophilic lactobacilli, since some strains colonize the human mucosal surfaces and contribute to their protection against pathogen invasion. Also, some strains have shown intrinsic immune-stimulatory properties. Therefore, these probiotic bacteria are ideal candidates for mucosal delivery of therapeutic and prophylactic molecules. However, it is very important to realize that the construction of genetically engineered lactobacilli as mucosal delivery vehicles must ensure the safety for human consumption and the stability of the cloned gene without selective pressure. Our group has developed a technology to generate food-grade recombinant lactobacilli that express very efficiently heterologous genes. Furthermore, a biological containment mechanism based in the deletion of the thyA gene has been developed. The resulting lactobacilli strains are unable to grow in the absence of thymidine, thus preventing their spread into the environment.The construction of a Lactobacillus casei strain that produces camelid antibodies against rotavirus will be presented.