Development of a Stress-Inducible Controlled Expression (SICE) system in Lactococcus lactis for the production and delivery of therapeutic molecules at mucosal surfaces

Bouasria Benbouziane; Pedro Ribelles; Camille Aubry; Rebeca Martin; Pascale Kharrat; Ali Riazi; Philippe Langella; Luis G Bermúdez-Humarán

doi:10.1016/j.jbiotec.2013.04.019

Development of a Stress-Inducible Controlled Expression (SICE) system in Lactococcus lactis for the production and delivery of therapeutic molecules at mucosal surfaces

J Biotechnol. 2013 Oct 20;168(2):120-9. doi: 10.1016/j.jbiotec.2013.04.019. Epub 2013 May 9.

Authors

Bouasria Benbouziane¹, Pedro Ribelles, Camille Aubry, Rebeca Martin, Pascale Kharrat, Ali Riazi, Philippe Langella, Luis G Bermúdez-Humarán

Affiliation

¹ 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.

PMID: 23664884
DOI: 10.1016/j.jbiotec.2013.04.019

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).

Keywords: Immunomodulation; Lactic acid bacteria; Lactococcus lactis; Recombinant heterologous production; Stress-inducible system.

MeSH terms

Administration, Oral
Administration, Rectal
Animals
Base Sequence
Disease Models, Animal
Female
Genetic Vectors*
Human papillomavirus 16 / immunology
Humans
Inflammatory Bowel Diseases / drug therapy*
Interleukin-10 / administration & dosage*
Interleukin-10 / genetics
Interleukin-10 / immunology
Interleukin-10 / metabolism*
Lactococcus lactis / genetics*
Lactococcus lactis / metabolism
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Mucous Membrane / metabolism
Organ Specificity
Papillomavirus Infections / prevention & control*
Papillomavirus Vaccines / administration & dosage*
Papillomavirus Vaccines / genetics
Plasmids
Recombinant Proteins / genetics
Recombinant Proteins / therapeutic use
Reproducibility of Results
Stress, Physiological
Vaccines, Synthetic

Substances

Papillomavirus Vaccines
Recombinant Proteins
Vaccines, Synthetic
Interleukin-10