Development of a food-grade Lactobacillus-based oral vaccine delivery system

In low-income countries, efforts to increase immunization coverage are hampered by weak health systems. Furthermore, the unaffordable costs of some vaccines remain a major barrier for people to access vaccination services. To develop novel technologies fo r effective production and delivery of vaccines with simplicity, safety and low cost is urgent and will help to scale up immunization coverage in the poorest countries, helping the global community to achieve the Millennium Development Goals. Live microbi al vaccine vehicles have the potential to become the cheapest and safest option for vaccination, because they are needle-free, easy to produce and distribute, and refrigerator free. As non-pathogenic probiotic food-grade bacteria, Lactobacillus plantarum strains have many advantages as vaccine vehicles, because they are widely used in the food industry, considered to be generally regarded as safe (GRAS), resistant against bile acid and low pH, and persistent in the gastrointestinal (GI)-tract. Furthermore , there are possibilities to construct conditionally lethal mutants, and to integrate all foreign DNA into the chromosome, thus avoiding the use of antibiotic selection markers. In this project, we will exploit our state-of-the-art knowledge on protein e xpression, secretion and anchoring in Lactobacilli to develop safe vectors for oral and/or nasal vaccine delivery, using tuberculosis and rotavirus antigens as model vaccines. We will select optimal promoters in order to achieve high vaccine expression in situ. Functional test will be done using both human cell cultures and mouse models.