Mucosal delivery of therapeutic and prophylactic molecules using lactic acid bacteria

• Published in: Nature reviews. Microbiology Vol. 6; no. 5; pp. 349 - 362
• Main Authors: Wells, Jerry M, Mercenier, Annick
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2008; Nature Publishing Group
• Subjects: Acids; Animals; Antigens; Bacteria; Bacterial vaccines; Biomedical and Life Sciences; Drug Delivery Systems - methods; Genetic aspects; Health aspects; Humans; Immune response; Immunity, Mucosal; Immunology; Infectious Diseases; Interleukin-10; Lactic Acid - biosynthesis; Lactobacillus; Lactobacillus - genetics; Lactobacillus - immunology; Lactococcus; Life Sciences; Lymphatic system; Medical Microbiology; Mice; Microbiology; Microbiota; Mucous Membrane - microbiology; Parasitology; Pathogens; Probiotics; Prophylaxis; Recombinant Proteins - genetics; Recombinant Proteins - immunology; Recombinant Proteins - therapeutic use; review-article; Streptococcaceae - genetics; Streptococcaceae - immunology; Vaccines; Vaccines, DNA - genetics; Vaccines, DNA - immunology; Vaccines, DNA - therapeutic use; Virology; Switzerland; Netherlands
• ISSN: 1740-1526; 1740-1534
• DOI: 10.1038/nrmicro1840

Key Points Important developments in the design of recombinant lactic acid bacteria (LAB) as mucosal carriers for a range of health-beneficial compounds, such as antigens, allergens, immune modulators, antimicrobial and trefoil peptides, single-chain antibodies and a few enzymes, have taken place in the past decade. The different approaches, strategies and proof-of-concept studies that have been conducted in animal models are reviewed in this article. The rationale for the use of lactic acid bacteria as mucosal delivery vehicles and key aspects of their interaction with the host mucosal surfaces are discussed. An overview of the progress in the field of LAB-based mucosal vaccines and a discussion of protection studies that have been conducted in rodents, mainly by intranasal and intragastric immunization, are provided. The latest developments in the use of LAB as vechicles for DNA vaccination are described. Studies that deal with successful delivery of cytokines or trefoil peptides to treat experimental colitis in rodents are reviewed. Notably, the first Phase I trial has been conducted with patients that suffer from inflammatory bowel disease using safe biologically contained recombinant lactococci that secrete human interleukin-10. Efforts to induce oral tolerance and develop preventive strategies against type I allergies using LAB are highlighted. Anti-infective strategies that are based on the delivery of microbicidal peptides are discussed, with a special emphasis on the prevention of HIV-1 infection. The concluding section captures the key learning points in the field, identifies major questions that remain to be answered and highlights challenges for the future. The development of lactic acid bacteria as delivery vehicles for therapeutics, anti-infectives and vaccines at mucosa is discussed in this Review. Engineered LAB could be deployed to treat conditions such as allergy and inflammatory bowel disease, and might also be adopted in the fight against pathogens, including HIV-1 infection. Studies of lactic acid bacteria (LAB) as delivery vehicles have focused mainly on the development of mucosal vaccines, with much effort being devoted to the generation of genetic tools for antigen expression in different bacterial locations. Subsequently, interleukins have been co-expressed with antigens in LAB to enhance the immune response that is raised against the antigen. LAB have also been used as a delivery system for a range of molecules that have different applications, including anti-infectives, therapies for allergic diseases and therapies for gastrointestinal diseases. Now that the first human trial with a Lactococcus strain that expresses recombinant interleukin-10 has been completed, we discuss what we have learnt, what we do not yet understand and what the future holds for therapy and prophylaxis with LAB.