UTILISATION DES BACTERIES LACTIQUES COMME VECTEURS DE PROTEINES D’INTERET MEDICAL.

Abstract

In recent years, Recombinant Lactic Acid Bacteria (LAB) have been successfully used as safe mucosal delivery vectors. In this work, we sought to implement an inducible expression system in the model LAB, L. lactis, suitable for the production and delivery of proteins of health interest in situ at mucosal surfaces. For this task, we wanted to design and implement a system in which protein expression is induced upon host administration, which will ensure production and delivery of the molecule of interest in situ. We decided to develop an expression system regulated by stress: Stress-Inducible Controlled Expression (SICE) system. Indeed, upon administration into the host, recombinant bacteria should find conditions very different from their usual culture conditions and then suffer different types of stress: including heat-stress (if the body temperature of the subject to be treated is high enough compared to the optimal growth temperature of the bacteria) and in the case of oral administration, the heat stress can be accompanied by an acid stress during passage through the stomach (where the pH is about 1.5–2.0) along with a bile stress in the duodenum. In addition, such a system represents an interesting alternative for the treatment of certain diseases such as IBD. The functionality of the SICE system was validated in vivo using two different routes of administration: oral and intranasal, and in two different murine models of human pathologies: (i) a model of therapy against Inflammatory Bowel Diseases (IBD) and (ii) a model of vaccination against human papillomavirus type-16 (HPV-16).