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Towards a
maize-based edible vaccine: LT-B-producing maize protects mice against Escherichia
coli heat labile enterotoxin (LT) and cholera toxin (CT)
R. Chikwamba, J.
Cunnick, D. Hathaway, J.
McMurray, H. Mason & K. Wang
Recent
advances in plant transformation have allowed the use of crop plants
beyond their traditional uses of feed and fiber.
We 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 mice by feeding transgenic maize meal expressing LT-B
or nontransgenic 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.
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