Mucosal delivery of therapeutic and prophylactic molecules using lactic acid bacteria (original) (raw)
Hayashi, H., Takahashi, R., Nishi, T., Sakamoto, M. & Benno, Y. Molecular analysis of jejunal, ileal, caecal and recto-sigmoidal human colonic microbiota using 16S rRNA gene libraries and terminal restriction fragment length polymorphism. J. Med. Microbiol.54, 1093–1101 (2005). ArticleCASPubMed Google Scholar
Lavelle, E. C. & O'Hagan, D. T. Delivery systems and adjuvants for oral vaccines. Expert Opin. Drug Deliv.3, 747–762 (2006). ArticleCASPubMed Google Scholar
Malik, D. K., Baboota, S., Ahuja, A., Hasan, S. & Ali, J. Recent advances in protein and peptide drug delivery systems. Curr. Drug Deliv.4, 141–151 (2007). ArticleCASPubMed Google Scholar
Wernerus, H. & Stahl, S. Biotechnological applications for surface-engineered bacteria. Biotechnol. Appl. Biochem.40, 209–228 (2004). ArticleCASPubMed Google Scholar
Uyen, N. Q., Hong, H. A. & Cutting, S. M. Enhanced immunisation and expression strategies using bacterial spores as heat-stable vaccine delivery vehicles. Vaccine25, 356–365 (2007). ArticleCASPubMed Google Scholar
Pozzi, G., Oggioni, M. R. & Medaglini, D. in Gram-positive bacteria as vaccine vehicles for mucosal immunisation (eds Pozzi, G. & Wells, J. M.) 35–60 (Landes, Austin, 1997). Book Google Scholar
Foligne, B. et al. Prevention and treatment of colitis with Lactococcus lactis secreting the immunomodulatory Yersinia LcrV protein Gastroenterology133, 862–874 (2007). Demonstrated a new strategy for the treatment of colitis in mice based on LAB delivery of an anti-inflammatory protein that was derived from a pathogen. ArticleCASPubMed Google Scholar
Frossard, C. P., Steidler, L. & Eigenmann, P. A. Oral administration of an IL-10-secreting Lactococcus lactis strain prevents food-induced IgE sensitization. J. Allergy Clin. Immunol.119, 952–959 (2007). ArticleCASPubMed Google Scholar
Hanniffy, S. B., Carter, A. T., Hitchin, E. & Wells, J. M. Mucosal delivery of a pneumococcal vaccine using Lactococcus lactis affords protection against respiratory infection. J. Infect. Dis.195, 185–193 (2007). Demonstrated that intranasal vaccination with the LAB vaccine provides better protection than purified antigen against respiratory infection with virulent pneumococci. Also showed that the killed LAB vaccine protects against infection. ArticleCASPubMed Google Scholar
Cortes-Perez, N. G. et al. Intranasal coadministration of live lactococci producing interleukin-12 and a major cow's milk allergen inhibits allergic reaction in mice. Clin. Vaccine Immunol.14, 226–233 (2007). ArticleCASPubMedPubMed Central Google Scholar
Braat, H. et al. A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn's disease. Clin. Gastroenterol. Hepatol.4, 754–759 (2006). First clinical trial to use recombinant LAB. Demonstrated that the containment strategy forL. lactisthat expresses recombinant IL-10 is effective and also that mucosal delivery of IL-10 byL. lactisis feasible in humans. ArticleCASPubMed Google Scholar
Neutra, M. R. & Kozlowski, P. A. Mucosal vaccines: the promise and the challenge. Nature Rev. Immunol.6, 148–158 (2006). ArticleCAS Google Scholar
Roland, K. L., Tinge, S. A., Killeen, K. P. & Kochi, S. K. Recent advances in the development of live, attenuated bacterial vectors. Curr. Opin. Mol. Ther.7, 62–72 (2005). CASPubMed Google Scholar
Daudel, D., Weidinger, G. & Spreng, S. Use of attenuated bacteria as delivery vectors for DNA vaccines. Expert Rev. Vaccines6, 97–110 (2007). ArticleCASPubMed Google Scholar
Tacket, C. O. & Levine, M. M. CVD 908, CVD 908-htrA, and CVD 909 live oral typhoid vaccines: a logical progression. Clin. Infect. Dis.45, S20–S23 (2007). ArticleCASPubMed Google Scholar
Mannam, P., Jones, K. F. & Geller, B. L. Mucosal vaccine made from live, recombinant Lactococcus lactis protects mice against pharyngeal infection with Streptococcus pyogenes. Infect. Immun.72, 3444–3450 (2004). Demonstrated that anL. lactisvaccine which expresses the conserved C-repeat region ofS. pyogenesM protein can protect mice against pharyngeal infection. ArticleCASPubMedPubMed Central Google Scholar
Gilbert, C., Robinson, K., Le Page, R. W. & Wells, J. M. Heterologous expression of an immunogenic pneumococcal type 3 capsular polysaccharide in Lactococcus lactis. Infect. Immun.68, 3251–3260 (2000). Demonstrated that expression of an operon which contains 3 of the 4 genes that are required for pneumococcal type 3 capsular-polysaccharide biosynthesis inL. lactisresulted in the production of 120 mg per litre of an immunogenic capsular polysaccharide. ArticleCASPubMedPubMed Central Google Scholar
Mowat, A. M., Millington, O. R. & Chirdo, F. G. Anatomical and cellular basis of immunity and tolerance in the intestine. J. Pediatr. Gastroenterol. Nutr.39, S723–S724 (2004). ArticlePubMed Google Scholar
Rescigno, M. et al. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nature Immunol.2, 361–367 (2001). ArticleCAS Google Scholar
Chieppa, M., Rescigno, M., Huang, A. Y. & Germain, R. N. Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TLR engagement. J. Exp. Med.203, 2841–2852 (2006). ArticleCASPubMedPubMed Central Google Scholar
Macpherson, A. J. & Uhr, T. Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science303, 1662–1665 (2004). Showed that the intragastric administration of GFP-expressingE. cloacae, a mouse commensal, results in the uptake of these bacteria by DCs in the Peyer's patches, and that these DCs traffic to the mesenteric lymph nodes. ArticleCASPubMed Google Scholar
Macpherson, A. J. IgA adaptation to the presence of commensal bacteria in the intestine. Curr. Top. Microbiol. Immunol.308, 117–136 (2006). CASPubMed Google Scholar
Klijn, N., Weerkamp, A. H. & de Vos, W. M. Genetic marking of Lactococcus lactis shows its survival in the human gastrointestinal tract. Appl. Environ. Microbiol.61, 2771–2774 (1995). CASPubMedPubMed Central Google Scholar
Vesa, T., Pochart, P. & Marteau, P. Pharmacokinetics of Lactobacillus plantarum NCIMB 8826, Lactobacillus fermentum KLD, and Lactococcus lactis MG 1363 in the human gastrointestinal tract. Aliment. Pharmacol. Ther.14, 823–828 (2000). ArticleCASPubMed Google Scholar
Alander, M. et al. Persistence of colonization of human colonic mucosa by a probiotic strain, Lactobacillus rhamnosus GG, after oral consumption. Appl. Environ. Microbiol.65, 351–354 (1999). CASPubMedPubMed Central Google Scholar
van der Waaij, L. A. et al. Bacterial population analysis of human colon and terminal ileum biopsies with 16S rRNA-based fluorescent probes: commensal bacteria live in suspension and have no direct contact with epithelial cells. Inflamm. Bowel Dis.11, 865–871 (2005). ArticlePubMed Google Scholar
Valeur, N., Engel, P., Carbajal, N., Connolly, E. & Ladefoged, K. Colonization and immunomodulation by Lactobacillus reuteri ATCC 55730 in the human gastrointestinal tract. Appl. Environ. Microbiol.70, 1176–1181 (2004). ArticleCASPubMedPubMed Central Google Scholar
Vinderola, C. G., Medici, M. & Perdigon, G. Relationship between interaction sites in the gut, hydrophobicity, mucosal immunomodulating capacities and cell wall protein profiles in indigenous and exogenous bacteria. J. Appl. Microbiol.96, 230–243 (2004). ArticleCASPubMed Google Scholar
Nouaille, S. et al. Heterologous protein production and delivery systems for Lactococcus lactis. Genet. Mol. Res.2, 102–111 (2003). PubMed Google Scholar
de Vos, W. M. Gene expression systems for lactic acid bacteria. Curr. Opin. Microbiol.2, 289–295 (1999). ArticleCASPubMed Google Scholar
Mercenier, A., Muller-Alouf, H. & Grangette, C. Lactic acid bacteria as live vaccines. Curr. Issues Mol. Biol.2, 17–25 (2000). CASPubMed Google Scholar
Norton, P. M. et al. Factors affecting the immunogenicity of tetanus toxin fragment C expressed in Lactococcus lactis. FEMS Immunol. Med. Microbiol.14, 167–177 (1996). ArticleCASPubMed Google Scholar
Hanniffy, S. et al. Potential and opportunities for use of recombinant lactic acid bacteria in human health. Adv. Appl. Microbiol.56, 1–64 (2004). ArticlePubMed Google Scholar
Robinson, K., Chamberlain, L. M., Schofield, K. M., Wells, J. M. & Le Page, R. W. Oral vaccination of mice against tetanus with recombinant Lactococcus lactis. Nature Biotechnol.15, 653–657 (1997). In this study, mice that were orally and intranasally administered withL. lactisthat expresses tetanus toxin fragment C antigen were protected from lethal systemic challenge with a 20LD50dose of tetanus toxin. Crucially, the killed LAB vaccine was shown to be just as immunogenic as the live LAB vaccine by the intranasal route, and tetanus toxin fragment C-specific IgA responses were elicited by the LAB vaccine. ArticleCAS Google Scholar
Norton, P. M., Wells, J. M., Brown, H. W., Macpherson, A. M. & Le Page, R. W. Protection against tetanus toxin in mice nasally immunized with recombinant Lactococcus lactis expressing tetanus toxin fragment C. Vaccine15, 616–619 (1997). ArticleCASPubMed Google Scholar
Grangette, C. et al. Mucosal immune responses and protection against tetanus toxin after intranasal immunization with recombinant Lactobacillus plantarum. Infect. Immun.69, 1547–1553 (2001). Demonstrated that serum titres to TTFC are dependent on the amount of antigen that is produced by recombinantL. plantarum. ArticleCASPubMedPubMed Central Google Scholar
Grangette, C. et al. Protection against tetanus toxin after intragastric administration of two recombinant lactic acid bacteria: impact of strain viability and in vivo persistence. Vaccine20, 3304–3309 (2002). ArticleCASPubMed Google Scholar
Shaw, D. M. et al. Engineering the microflora to vaccinate the mucosa: serum immunoglobulin G responses and activated draining cervical lymph nodes following mucosal application of tetanus toxin fragment C-expressing lactobacilli. Immunology100, 510–518 (2000). ArticleCASPubMedPubMed Central Google Scholar
Grangette, C. et al. Enhanced mucosal delivery of antigen with cell wall mutants of lactic acid bacteria. Infect. Immun.72, 2731–2737 (2004). Showed that the immunogenicity of TTFC could be substantially improved by using alanine racemase mutants ofL. plantarum. ArticleCASPubMedPubMed Central Google Scholar
Lee, M. H., Roussel, Y., Wilks, M. & Tabaqchali, S. Expression of Helicobacter pylori urease subunit B gene in Lactococcus lactis MG1363 and its use as a vaccine delivery system against H. pylori infection in mice. Vaccine19, 3927–3935 (2001). ArticleCASPubMed Google Scholar
Dieye, Y. et al. Ability of Lactococcus lactis to export viral capsid antigens: a crucial step for development of live vaccines. Appl. Environ. Microbiol.69, 7281–7288 (2003). ArticleCASPubMedPubMed Central Google Scholar
Bermudez-Humaran, L. G. et al. An inducible surface presentation system improves cellular immunity against human papillomavirus type 16 E7 antigen in mice after nasal administration with recombinant lactococci. J. Med. Microbiol.53, 427–433 (2004). ArticleCASPubMed Google Scholar
Robinson, K. et al. Mucosal and cellular immune responses elicited by recombinant Lactococcus lactis strains expressing tetanus toxin fragment C. Infect. Immun.72, 2753–2761 (2004). Revealed that intranasally administeredL. lactisthat expresses tetanus toxin fragment C elicits a tetanus toxin fragment C-specific T-cell response, which has a mixed profile of TH1 and TH2 cytokines in the intestine and a tetanus toxin fragment C-specific IgA response at more than one mucosal site. ArticleCASPubMedPubMed Central Google Scholar
Delcenserie, V. et al. Immunomodulatory effects of probiotics in the intestinal tract. Curr. Issues Mol. Biol.10, 37–54 (2008). CASPubMed Google Scholar
Steidler, L. et al. Secretion of biologically active murine interleukin-2 by Lactococcus lactis subsp. lactis. Appl. Environ. Microbiol.61, 1627–1629 (1995). CASPubMedPubMed Central Google Scholar
Steidler, L. et al. Mucosal delivery of murine interleukin-2 (IL-2) and IL-6 by recombinant strains of Lactococcus lactis coexpressing antigen and cytokine. Infect. Immun.66, 3183–3189 (1998). First demonstration that the secretion of cytokines inL. lactistogether with the intracellular production of an antigen can enhance immune responses. CASPubMedPubMed Central Google Scholar
Bermudez-Humaran, L. G. et al. A novel mucosal vaccine based on live Lactococci expressing E7 antigen and IL-12 induces systemic and mucosal immune responses and protects mice against human papillomavirus type 16-induced tumors. J. Immunol.175, 7297–7302 (2005). Demonstrated therapeutic immunization with a recombinantL. lactiscancer vaccine in a mouse model of human papillomavirus type 16-induced tumours. ArticleCASPubMed Google Scholar
Cheun, H. I. et al. Protective immunity of SpaA-antigen producing Lactococcus lactis against Erysipelothrix rhusiopathiae infection. J. Appl. Microbiol.96, 1347–1353 (2004). ArticleCASPubMed Google Scholar
Xin, K. Q. et al. Immunogenicity and protective efficacy of orally administered recombinant Lactococcus lactis expressing surface-bound HIV Env. Blood102, 223–228 (2003). ArticleCASPubMed Google Scholar
Corthesy, B., Boris, S., Isler, P., Grangette, C. & Mercenier, A. Oral immunization of mice with lactic acid bacteria producing Helicobacter pylori urease B subunit partially protects against challenge with Helicobacter felis. J. Infect. Dis.192, 1441–1449 (2005). ArticleCASPubMed Google Scholar
Oliveira, M. L. et al. Induction of systemic and mucosal immune response and decrease in Streptococcus pneumoniae colonization by nasal inoculation of mice with recombinant lactic acid bacteria expressing pneumococcal surface antigen A. Microbes Infect.8, 1016–1024 (2006). ArticleCASPubMedPubMed Central Google Scholar
Jechlinger, W. Optimization and delivery of plasmid DNA for vaccination. Expert Rev. Vaccines5, 803–825 (2006). ArticleCASPubMed Google Scholar
Howarth, M. & Elliott, T. The processing of antigens delivered as DNA vaccines. Immunol. Rev.199, 27–39 (2004). ArticleCASPubMed Google Scholar
Guimaraes, V. D. et al. Internalin-expressing Lactococcus lactis is able to invade small intestine of guinea pigs and deliver DNA into mammalian epithelial cells. Microbes Infect.7, 836–844 (2005). Revealed thatL. lactiswhich expresses an invasin can deliver a DNA-vaccine vector into epithelial cells. ArticleCASPubMed Google Scholar
Guimaraes, V. D. et al. Use of native lactococci as vehicles for delivery of DNA into mammalian epithelial cells. Appl. Environ. Microbiol.72, 7091–7097 (2006). ArticleCASPubMedPubMed Central Google Scholar
Li, Y. G., Tian, F. L., Gao, F. S., Tang, X. S. & Xia, C. Immune responses generated by Lactobacillus as a carrier in DNA immunization against foot-and-mouth disease virus. Vaccine25, 902–911 (2007). ArticleCASPubMed Google Scholar
Steidler, L. et al. Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. Science289, 1352–1355 (2000). Showed that IL-10-secreting lactococci can be used therapeutically in two models of murine colitis. ArticleCASPubMed Google Scholar
Steidler, L. In situ delivery of cytokines by genetically engineered Lactococcus lactis. Antonie Van Leeuwenhoek82, 323–331 (2002). ArticleCASPubMed Google Scholar
Schreiber, S. et al. Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn's disease. Crohn's disease IL-10 cooperative study group. Gastroenterology119, 1461–1472 (2000). ArticleCASPubMed Google Scholar
Steidler, L. et al. Biological containment of genetically modified Lactococcus lactis for intestinal delivery of human interleukin 10. Nature Biotechnol.21, 785–789 (2003). Describes the development of a biological-containment system forL. lactisthat was based on replacement of the thymidylate synthase gene with a heterologous gene. ArticleCAS Google Scholar
Vandenbroucke, K. et al. Active delivery of trefoil factors by genetically modified Lactococcus lactis prevents and heals acute colitis in mice. Gastroenterology127, 502–513 (2004). ArticleCASPubMed Google Scholar
Crameri, R. & Rhyner, C. Novel vaccines and adjuvants for allergen-specific immunotherapy. Curr. Opin. Immunol.18, 761–768 (2006). ArticleCASPubMed Google Scholar
Murosaki, S. et al. Heat-killed Lactobacillus plantarum L-137 suppresses naturally fed antigen-specific IgE production by stimulation of IL-12 production in mice. J. Allergy Clin. Immunol.102, 57–64 (1998). ArticleCASPubMed Google Scholar
Kruisselbrink, A., Heijne Den Bak-Glashouwer, M. J., Havenith, C. E., Thole, J. E. & Janssen, R Recombinant Lactobacillus plantarum inhibits house dust mite-specific T-cell responses. Clin. Exp. Immunol.126, 2–8 (2001). ArticleCASPubMedPubMed Central Google Scholar
Repa, A. et al. Mucosal co-application of lactic acid bacteria and allergen induces counter-regulatory immune responses in a murine model of birch pollen allergy. Vaccine22, 87–95 (2003). ArticleCASPubMed Google Scholar
Chatel, J. M. et al. Characterization of a Lactococcus lactis strain that secretes a major epitope of bovine beta-lactoglobulin and evaluation of its immunogenicity in mice. Appl. Environ. Microbiol.69, 6620–6627 (2003). ArticleCASPubMedPubMed Central Google Scholar
Novak, N., Allam, J. P., Betten, H., Haberstok, J. & Bieber, T. The role of antigen presenting cells at distinct anatomic sites: they accelerate and they slow down allergies. Allergy59, 5–14 (2004). ArticleCASPubMed Google Scholar
Adel-Patient, K. et al. Oral administration of recombinant Lactococcus lactis expressing bovine β-lactoglobulin partially prevents mice from sensitization. Clin. Exp. Allergy35, 539–546 (2005). ArticleCASPubMed Google Scholar
Daniel, C. et al. Modulation of allergic immune responses by mucosal application of recombinant lactic acid bacteria producing the major birch pollen allergen Bet v 1. Allergy61, 812–819 (2006). ArticleCASPubMed Google Scholar
Daniel, C., Repa, A., Mercenier, A., Wiedermann, U. & Wells, J. The European LABDEL project and its relevance to the prevention and treatment of allergies. Allergy62, 1237–1242 (2007). ArticleCASPubMed Google Scholar
Charng, Y. C., Lin, C. C. & Hsu, C. H. Inhibition of allergen-induced airway inflammation and hyperreactivity by recombinant lactic-acid bacteria. Vaccine24, 5931–5936 (2006). ArticleCASPubMed Google Scholar
Huibregtse, I. L. et al. Induction of ovalbumin-specific tolerance by oral administration of Lactococcus lactis secreting ovalbumin. Gastroenterology133, 517–528 (2007). ArticleCASPubMed Google Scholar
Wu, C. et al. Immunomodulatory effects of IL-12 secreted by Lactococcus lactis on Th1/Th2 balance in ovalbumin (OVA)-induced asthma model mice. Int. Immunopharmacol.6, 610–615 (2006). ArticleCASPubMed Google Scholar
Boyd, M. R. et al. Discovery of cyanovirin-N, a novel human immunodeficiency virus-inactivating protein that binds viral surface envelope glycoprotein gp120: potential applications to microbicide development. Antimicrob. Agents Chemother.41, 1521–1530 (1997). ArticleCASPubMedPubMed Central Google Scholar
Giomarelli, B. et al. The microbicide cyanovirin-N expressed on the surface of commensal bacterium Streptococcus gordonii captures HIV-1. Aids16, 1351–1356 (2002). ArticleCASPubMed Google Scholar
Pusch, O. et al. Bioengineering lactic acid bacteria to secrete the HIV-1 virucide cyanovirin. J. Acquir. Immune Defic. Syndr.40, 512–520 (2005). L. lactisthat secretes cyanovirin was shown to block HIV-1 infectionin vitro. ArticleCASPubMed Google Scholar
Liu, X. et al. Engineered vaginal lactobacillus strain for mucosal delivery of the human immunodeficiency virus inhibitor cyanovirin-N. Antimicrob. Agents Chemother.50, 3250–3259 (2006). ArticleCASPubMedPubMed Central Google Scholar
Chang, T. L. et al. Inhibition of HIV infectivity by a natural human isolate of Lactobacillus jensenii engineered to express functional two-domain CD4. Proc. Natl Acad. Sci. USA100, 11672–11677 (2003). Demonstrated that LAB can produce a CD4 receptor that can bind HIV-1in vitro. ArticleCASPubMedPubMed Central Google Scholar
Chancey, C. J. et al. Lactobacilli-expressed single-chain variable fragment (scFv) specific for intercellular adhesion molecule 1 (ICAM-1) blocks cell-associated HIV-1 transmission across a cervical epithelial monolayer. J. Immunol.176, 5627–5636 (2006). ArticleCASPubMed Google Scholar
Rao, S. et al. Toward a live microbial microbicide for HIV: commensal bacteria secreting an HIV fusion inhibitor peptide. Proc. Natl Acad. Sci. USA102, 11993–11998 (2005). ArticleCASPubMedPubMed Central Google Scholar
Pusch, O. et al. An anti-HIV microbicide engineered in commensal bacteria: secretion of HIV-1 fusion inhibitors by lactobacilli. Aids20, 1917–1922 (2006). ArticleCASPubMed Google Scholar
Falagas, M. E., Betsi, G. I. & Athanasiou, S. Probiotics for the treatment of women with bacterial vaginosis. Clin. Microbiol. Infect.13, 657–664 (2007). ArticleCASPubMed Google Scholar
Chakraborty, H. et al. Viral burden in genital secretions determines male-to-female sexual transmission of HIV-1: a probabilistic empiric model. Aids15, 621–627 (2001). ArticleCASPubMed Google Scholar
Beninati, C. et al. Therapy of mucosal candidiasis by expression of an anti-idiotype in human commensal bacteria. Nature Biotechnol.18, 1060–1064 (2000). First example of LAB delivery of a microbicidal antibody and its use for the treatment of candidiasis in a rat model. ArticleCAS Google Scholar
Kruger, C. et al. In situ delivery of passive immunity by lactobacilli producing single-chain antibodies. Nature Biotechnol.20, 702–706 (2002). Demonstrated passive immunotherapy against dental caries by blocking the adhesion ofS. mutanswith LAB that express an scFv. ArticleCAS Google Scholar
Oliveira, M. L., Areas, A. P. & Ho, P. L. Intranasal vaccines for protection against respiratory and systemic bacterial infections. Expert Rev. Vaccines6, 419–429 (2007). ArticleCASPubMed Google Scholar
Baumann, U., Gocke, K., Gewecke, B., Freihorst, J. & von Specht, B. U. Assessment of pulmonary antibodies with induced sputum and bronchoalveolar lavage induced by nasal vaccination against Pseudomonas aeruginosa: a clinical phase I/II study. Respir. Res.8, 57 (2007). ArticleCASPubMedPubMed Central Google Scholar
DiGiandomenico, A. et al. Intranasal immunization with heterologously expressed polysaccharide protects against multiple Pseudomonas aeruginosa infections. Proc. Natl Acad. Sci. USA104, 4624–4629 (2007). ArticleCASPubMedPubMed Central Google Scholar
Drouault, S., Juste, C., Marteau, P., Renault, P. & Corthier, G. Oral treatment with Lactococcus lactis expressing Staphylococcus hyicus lipase enhances lipid digestion in pigs with induced pancreatic insufficiency. Appl. Environ. Microbiol.68, 3166–3168 (2002). ArticleCASPubMedPubMed Central Google Scholar
Han, W. et al. Improvement of an experimental colitis in rats by lactic acid bacteria producing superoxide dismutase. Inflamm. Bowel Dis.12, 1044–1052 (2006). ArticlePubMed Google Scholar
Salminen, S. et al. Demonstration of safety of probiotics — a review. Int. J. Food Microbiol.44, 93–106 (1998). ArticleCASPubMed Google Scholar
Ishibashi, N. & Yamazaki, S. Probiotics and safety. Am. J. Clin. Nutr.73, (Suppl. 2) 465–470 (2001). Article Google Scholar
Frey, J. Biological safety concepts of genetically modified live bacterial vaccines. Vaccine25, 5598–5605 (2007). ArticleCASPubMed Google Scholar
Perez-Alvarez, L. et al. Long-term monitoring of genotypic and phenotypic resistance to T20 in treated patients infected with HIV-1. J. Med. Virol.78, 141–147 (2006). ArticleCASPubMed Google Scholar
Lee, S. F. Oral colonization and immune responses to Streptococcus gordonii: potential use as a vector to induce antibodies against respiratory pathogens. Curr. Opin. Infect. Dis.16, 231–235 (2003). ArticleCASPubMed Google Scholar
Wells, J. M., Wilson, P. W., Norton, P. M., Gasson, M. J. & Le Page, R. W. Lactococcus lactis: high-level expression of tetanus toxin fragment C and protection against lethal challenge. Mol. Microbiol.8, 1155–1162 (1993). ArticleCASPubMed Google Scholar
Chu, H. et al. Lactobacillus acidophilus expressing recombinant K99 adhesive fimbriae has an inhibitory effect on adhesion of enterotoxigenic Escherichia coli. Microbiol. Immunol.49, 941–948 (2005). ArticleCASPubMed Google Scholar
Lee, J. S. et al. Mucosal immunization with surface-displayed severe acute respiratory syndrome coronavirus spike protein on Lactobacillus casei induces neutralizing antibodies in mice. J. Virol.80, 4079–4087 (2006). ArticleCASPubMedPubMed Central Google Scholar
Perez, C. A., Eichwald, C., Burrone, O. & Mendoza, D. Rotavirus vp7 antigen produced by Lactococcus lactis induces neutralizing antibodies in mice. J. Appl. Microbiol.99, 1158–1164 (2005). ArticleCASPubMed Google Scholar
Buccato, S. et al. Use of Lactococcus lactis expressing pili from group B Streptococcus as a broad-coverage vaccine against streptococcal disease. J. Infect. Dis.194, 331–340 (2006). ArticleCASPubMed Google Scholar
Pontes, D. S. et al. Induction of partial protection in mice after oral administration of Lactococcus lactis producing Brucella abortus L7/L12 antigen. J. Drug Target.11, 489–493 (2003). ArticleCASPubMed Google Scholar
Poo, H. et al. Oral administration of human papillomavirus type 16 E7 displayed on Lactobacillus casei induces E7-specific antitumor effects in C57/BL6 mice. Int. J. Cancer119, 1702–1709 (2006). ArticleCASPubMed Google Scholar
Zhang, Z. H., Jiang, P. H., Li, N. J., Shi, M. & Huang, W. Oral vaccination of mice against rodent malaria with recombinant Lactococcus lactis expressing MSP-119 . World J. Gastroenterol.11, 6975–6980 (2005). ArticleCASPubMedPubMed Central Google Scholar