TY - JOUR
T1 - A functional antigen in a practical crop
T2 - LT-B producing maize protects mice against Escherichia coli heat labile enterotoxin (LT) and cholera toxin (CT)
AU - Chikwamba, Rachel
AU - Cunnick, Joan
AU - Hathaway, Diane
AU - McMurray, Jennifer
AU - Mason, Hugh
AU - Wang, Kan
N1 - Funding Information:
We are grateful to John Clements of the Tulane University Medical Center for providing LT-B, LT toxin, and technical input on mice handling procedures. We thank Brian Larkins for providing the gamma zein promoter, Dwayne Kirk for facilitating our collaboration with the Boyce Thompson Institute for Plant Research, Bronwyn Frame and Sue Ellen Pegg for performing maize transformation and greenhouse maintenance of transgenic maize, and Paul Scott for advising in maize kernel protein analysis and critically reviewing the manuscript. Rachel Chikwamba is supported by the Rockefeller Foundation as a graduate student. This work was supported by USDA grant number 99-35504-7799. Journal Paper No. J-19578 of the Iowa Agriculture and Home Economics Experiment Station, Ames, Iowa, Project No. 3703, and supported by Hatch Act and State of Iowa.
PY - 2002/10
Y1 - 2002/10
N2 - We have produced a functional heat labile enterotoxin (LT-) B subunit of Escherichia coli in maize. LT-B is a multimeric protein that presents an ideal model for an edible vaccine, displaying stability in the gut and inducing mucosal and systemic immune responses. Transgenic maize was engineered to synthesize the LT-B polypeptides, which assembled into oligomeric structures with affinity for GM1 gangliosides. We orally immunized BALB/c mice by feeding transgenic maize meal expressing LT-B or non-transgenic maize meal spiked with bacterial LT-B. Both treatments stimulated elevated IgA and IgG antibodies against LT-B and the closely related cholera toxin B subunit (CT-B) in serum, and elevated IgA in fecal pellets. The transgenic maize induced a higher anti-LT-B and anti-CT-B mucosal and serum IgA response compared to the equivalent amount of bacterial LT-B spiked into maize. Following challenge by oral administration of the diarrhea inducing toxins LT and CT, transgenic maize-fed mice displayed reduced fluid accumulation in the gut compared to non-immunized mice. Moreover, the gut to carcass ratio of immunized mice was not significantly different from the PBS (non-toxin) challenged control group. We concluded that maize-synthesized LT-B had features of the native bacterial LT-B such as molecular weight, GM1 binding ability, and induction of serum and mucosal immunity. We have demonstrated that maize, a major food and feed ingredient, can be efficiently transformed to produce, accumulate, and store a fully assembled and functional candidate vaccine antigen.
AB - We have produced a functional heat labile enterotoxin (LT-) B subunit of Escherichia coli in maize. LT-B is a multimeric protein that presents an ideal model for an edible vaccine, displaying stability in the gut and inducing mucosal and systemic immune responses. Transgenic maize was engineered to synthesize the LT-B polypeptides, which assembled into oligomeric structures with affinity for GM1 gangliosides. We orally immunized BALB/c mice by feeding transgenic maize meal expressing LT-B or non-transgenic maize meal spiked with bacterial LT-B. Both treatments stimulated elevated IgA and IgG antibodies against LT-B and the closely related cholera toxin B subunit (CT-B) in serum, and elevated IgA in fecal pellets. The transgenic maize induced a higher anti-LT-B and anti-CT-B mucosal and serum IgA response compared to the equivalent amount of bacterial LT-B spiked into maize. Following challenge by oral administration of the diarrhea inducing toxins LT and CT, transgenic maize-fed mice displayed reduced fluid accumulation in the gut compared to non-immunized mice. Moreover, the gut to carcass ratio of immunized mice was not significantly different from the PBS (non-toxin) challenged control group. We concluded that maize-synthesized LT-B had features of the native bacterial LT-B such as molecular weight, GM1 binding ability, and induction of serum and mucosal immunity. We have demonstrated that maize, a major food and feed ingredient, can be efficiently transformed to produce, accumulate, and store a fully assembled and functional candidate vaccine antigen.
KW - Functional LT-B
KW - Oral immunization
KW - Plant-synthesized edible vaccine
KW - Serum and mucosal immunity
KW - Transgenic maize
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U2 - 10.1023/A:1020393426750
DO - 10.1023/A:1020393426750
M3 - Article
C2 - 12437079
AN - SCOPUS:0036774095
VL - 11
SP - 479
EP - 493
JO - Transgenic Research
JF - Transgenic Research
SN - 0962-8819
IS - 5
ER -