Production of Escherichia coli heat labile toxin (LT) B subunit in soybean seed and analysis of its immunogenicity as an oral vaccine.
The B subunit of the heat labile toxin of enterotoxigenic Escherichia coli (LTB) was used as a model immunogen for production in soybean seed. LTB expression was directed to the endoplasmic reticulum (ER) of seed storage parenchyma cells for sequestration in de novo synthesized inert protein accretions derived from the ER. Pentameric LTB accumulated to 2.4% of the total seed protein at maturity and was stable in desiccated seed. LTB-soybean extracts administered orally to mice induced both systemic IgG and IgA, and mucosal IgA antibody responses, and was particularly efficacious when used in a parenteral prime-oral gavage boost immunization strategy. Sera from immunized mice blocked ligand binding in vitro and immunized mice exhibited partial protection against LT challenge. Moreover, soybean-expressed LTB stimulated the antibody response against a co-administered antigen by 500-fold. These results demonstrate the utility of soybean as an efficient production platform for vaccines that can be used for oral delivery.
Moravec
Tomas
T
Donald Danforth Plant Science Center, 975 North Warson Road, St. Louis, MO 63132, United States.
Schmidt
Monica A
MA
Herman
Eliot M
EM
Woodford-Thomas
Terry
T
D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D004768:Enterotoxins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D004926:Escherichia coli / Q000276:immunology; D004927:Escherichia coli Infections / Q000517:prevention & control; D029968:Escherichia coli Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D022361:Escherichia coli Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D005260:Female; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D010936:Plant Extracts / Q000008:administration & dosage / Q000276:immunology; D030821:Plants, Genetically Modified; D012639:Seeds / Q000235:genetics / Q000378:metabolism*; D013025:Glycine max / Q000235:genetics / Q000378:metabolism*; D022462:Vaccines, Edible / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D022361:Escherichia coli Vaccines; D010936:Plant Extracts; D022462:Vaccines, Edible; C027538:heat-labile enterotoxin, E coli