title: Development of a Stress-Inducible Controlled Expression (SICE) system in Lactococcus lactis for the production and delivery of therapeutic molecules at mucosal surfaces.
abstract: In recent years, recombinant lactic acid bacteria (LAB) have been successfully used as safe mucosal delivery vectors. Herein, we report on the development of a Stress-Inducible Controlled Expression (SICE) system in L. lactis for the production and delivery of proteins of health interest (both therapeutic and vaccine related) at mucosal surfaces. This system is episomal in nature and is composed of a vector carrying an expression cassette under the transcriptional control of a stress-inducible promoter. 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).
authors.affiliation: INRA, Commensal and Probiotics-Host Interactions Laboratory, UMR 1319 Micalis, F-78350 Jouy-en-Josas, France; AgroParisTech, UMR1319 Micalis, F-78350 Jouy-en-Josas, France; Laboratoire des Microorganismes Bénéfiques, des Aliments Fonctionnels et de la Santé (LMBAFS), Laboratory of Beneficial Microorganisms, Functional Foods and Health, Department of Biotechnology, University of Mostaganem, Lahcen Street, P.O. Box 300, Mostaganem 27000, Algeria.
authors.forename: Bouasria
authors.initials: B
authors.lastname: Benbouziane
authors.forename: Pedro
authors.initials: P
authors.lastname: Ribelles
authors.forename: Camille
authors.initials: C
authors.lastname: Aubry
authors.forename: Rebeca
authors.initials: R
authors.lastname: Martin
authors.forename: Pascale
authors.initials: P
authors.lastname: Kharrat
authors.forename: Ali
authors.initials: A
authors.lastname: Riazi
authors.forename: Philippe
authors.initials: P
authors.lastname: Langella
authors.forename: Luis G
authors.initials: LG
authors.lastname: Bermúdez-Humarán
mesh_terms: D000284:Administration, Oral; D000285:Administration, Rectal; D000818:Animals; D001483:Base Sequence; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors; D052162:Human papillomavirus 16 / Q000276:immunology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D016753:Interleukin-10 / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013294:Lactococcus lactis / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009092:Mucous Membrane / Q000378:metabolism; D009928:Organ Specificity; D030361:Papillomavirus Infections / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage* / Q000235:genetics; D010957:Plasmids; D011994:Recombinant Proteins / Q000235:genetics / Q000627:therapeutic use; D015203:Reproducibility of Results; D013312:Stress, Physiological; D014614:Vaccines, Synthetic
chemical_list: D053918:Papillomavirus Vaccines; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D016753:Interleukin-10
keywords: Immunomodulation; Lactic acid bacteria; Lactococcus lactis; Recombinant heterologous production; Stress-inducible system