Recombinant Escherichia coli expressing invasin targets the Peyer's patches: the basis for a bacterial formulation for oral vaccination.
We have investigated the tropism of nonpathogenic recombinant invasive Escherichia coli in the gastrointestinal tract and the efficacy of this invasive E. coli as an oral vaccine for cancer immunotherapy. E. coli expressing invasin from Yersinia pseudotuberculosis selectively invade nonphagocytic cells in which beta(1)-integrin is expressed and accessible. Following internalization the E. coli are degraded in the phagosome. Coexpression of listeriolysin O (LLO) mediates release of the content of the bacteria into the cytosol of the invaded cell. In vitro and in vivo experiments demonstrated that gut epithelial cells failed to be invaded by invasive E. coli, due to a basolateral localization of beta(1)-integrin. By contrast, selective uptake of invasive bacteria from the intestinal lumen into Peyer's patches was observed ex vivo. Once in this structure, invasive E. coli colocalized with dendritic cells and possibly B cells. Oral administration of invasive E. coli coexpressing the model antigen ovalbumin and LLO from Listeria monocytogenes was able to elicit systemic protection against a lethal challenge of B16 tumor cells expressing ovalbumin. These data demonstrate the selectivity of invasin-mediated invasion to the Peyer's patches and indicate the potential of nonpathogenic, invasive E. coli as an oral vaccine with applications in immunotherapy.
Centre for Molecular Oncology, Institute of Cancer and CR-UK Clinical Centre, Barts and The London, Queen Mary's School of Medicine and Dentistry, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, UK.
Rebecca J
RJ
Critchley-Thorne
Andrew J
AJ
Stagg
Georges
G
Vassaux
D018829:Adhesins, Bacterial / Q000235:genetics* / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000382:microbiology; D000951:Antigens, Neoplasm / Q000276:immunology; D001427:Bacterial Toxins / Q000378:metabolism; D018938:Caco-2 Cells; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D004926:Escherichia coli / Q000235:genetics / Q000502:physiology*; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism; D006460:Hemolysin Proteins; D006801:Humans; D018928:Immunity, Mucosal; D016233:Immunotherapy, Active / Q000379:methods*; D066298:In Vitro Techniques; D019012:Integrin beta1 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008546:Melanoma, Experimental / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D010581:Peyer's Patches / Q000276:immunology / Q000382:microbiology*; D019108:Tight Junctions / Q000187:drug effects / Q000648:ultrastructure; D014169:Transformation, Bacterial
D018829:Adhesins, Bacterial; D000951:Antigens, Neoplasm; D001427:Bacterial Toxins; D019496:Cancer Vaccines; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D019012:Integrin beta1; C053476:invasin, Yersinia; C038705:hlyA protein, Listeria monocytogenes