One Potato, Two Potato, Three Potato, Four . . .
June 15, 1998
One Potato, Two Potato, Three Potato, Four . . .
ABSTRACT & COMMENTARY
Source: Tacket CO, et al. Immunogenicity in humans of a recombinant bacterial antigen delivered in a transgenic potato. Nature Med 1998;4:607-609.
"What I say is that, if a fellow really likes potatoes, he must be a pretty decent sort of fellow." -A. A. Milne (1882-1956), In "Not That it Matters."
Tacket and colleagues examined the immunogenicity of an orally administered vaccine designed to provide protection against diarrhea due to a heat labile enterotoxin (LT-B) of enterotoxigenic Escherichia coli. LT-B was delivered in a potato (Frito Lay variety, 1607) made transgenic by a plant transformation vector containing a construct of the E. coli LT-B gene. Eleven of the subjects received either 100 g or 50 g of transgenic potato, while three subjects ingested wild-type potato. Each dose of transgenic potato contained 0.4-1.1 mg (mean, 0.75 mg/dose).
Evidence of immunogenicity of the vaccine included the appearance of gut-derived antibody secreting cells in the peripheral blood. These cells, which are a reflection of immunologic priming of the gut mucosal immune system, produced IgA and IgG anti-LT antibody. In addition, 10 of the 11 recipients of transgenic potato developed four-fold rises in IgG anti-LT titer, and six had similar increases in IgA anti-LT titer. Eight of the 11 also developed anti-LT neutralizing antibody titers greater than 1:100. Five of 10 recipients of transgenic potato experienced a four-fold or greater rise in anti-LT secretory IgA titer in their stool.
COMMENT BY STAN DERESINSKI, MD, FACP
E. coli LT-B is a pentamer of five subunits that collectively bind to GM1 gangliosides on the enteric surface of mucosal epithelial cells. The LT-A monomer then enters the cell where it acts by ADP-ribosylating a G protein and activating adenyl cyclase, leading to loss of cell water. Prevention of binding by LT-B interrupts the pathogenic mechanisms of enterotoxigenic E coli, a common cause of diarrhea.
This study demonstrates that delivery of a vaccine by the gastrointestinal route in the form of an edible transgenic plant is immunogenic in humans, producing evidence of both mucosal and systemic immune responses. The cholera toxin B subunit pentamer, almost identical to the E. coli LT-B, has also been expressed in a transgenic potato and produced partial protection after oral administration to mice (Arakawa T, et al. Efficacy of a food plant-based oral cholera toxin B subunit vaccine. Nat Biotechnol 1998;16:292-297). The Norwalk virus capsid protein has been expressed in both a transgenic potato and a transgenic tobacco plant, and has similarly been demonstrated to be immunogenic after oral administration to mice (Mason HS, et al. Expression of Norwalk virus capsid protein in transgenic tobacco and potato and its oral immunogenicity in mice. Proc Natl Acad Sci U S A 1996;93:5335-5340).
The ability to deliver an immunogenic vaccine by ingestion of a plant represents a significant medical and public health advance. It provides the opportunity for lowering vaccine cost and avoiding the need for injection devices. A problem with a transgenic potato, however, is that it may not be the most logical choice for use in infants. For that reason, the use of the banana is being considered as "protein production factories." Bananas are commonly eaten raw and do not require dental mastication.
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