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April J. Beyer,¹ Kan Wang,² Amber N. Umble,¹ Jeffrey D. Wolt,³ and Joan E. Cunnick^1,4

¹Interdepartmental Microbiology, Iowa State University, Ames, Iowa, USA; ²Plant Transformation Facility, Department of Agronomy, Iowa State University, Ames, Iowa, USA; ³Biosafety Institute for Genetically Modified Agricultural Products, Iowa State University, Ames, Iowa, USA; ⁴Department of Animal Sciences, Iowa State University, Ames, Iowa, USA

Abstract
Background: Transgenic maize, which produces the nontoxic B subunit of the Escherichia coli heat-labile toxin (LT-B) in seed, has proven to be an effective oral immunogen in mice. Currently, there is considerable concern over accidental consumption of transgenic maize expressing LT-B by humans and domestic animals. We have yet to define nonimmunogenic levels of transgenic LT-B when ingested.

Objectives: Our goal in this study was to determine the highest dose of LT-B orally administered in mice that does not result in a measurable immune response. We defined an immune response as specific serum or mucosal IgG or IgA significantly greater than background after three feedings (0.0002–20 µg) or a priming response induced by the intermittent feeding.

Methods: We fed transgenic maize pellets on days 0, 7, 21, and 49 and collected serum and fecal samples weekly. Serum was analyzed for LT-B–specific IgG and IgA, and feces was analyzed for LT-B–specific IgA.

Results: We observed a dose-dependent anti-LT-B antibody response with high specific antibody concentrations in groups fed high doses (0.2, 2, 20 µg) of LT-B maize. Mice fed 0.02 µg LT-B demonstrated immune priming in 62.5% of the animals. Mice that were fed ≤ 0.002 µg LT-B showed no increase in specific antibody nor did they demonstrate immune priming, indicating that 0.002 µg LT-B was the highest nonimmunogenic dose tested.

Conclusion: Our results demonstrate that LT-B derived from transgenic maize is immunogenic at nanogram levels when orally administered to mice.

Key words: adulterated food, genetically modified organism, heat-labile toxin, inadvertent exposure, oral vaccine, plant vaccine, transgenic maize, transgenic plant. Environ Health Perspect 115:354–360 (2007) . doi:10.1289/ehp.9687 available via http://dx.doi.org/ [Online 19 December 2006]

Address correspondence to J. Cunnick, Interdepartmental Microbiology, Iowa State University, 207 Science I, Ames, IA 50011 USA. Telephone: (515) 294-2070. Fax: (515) 294-6019. E-mail: jcunnick@iastate.edu

We thank J. Clements for supplying bacterial LT-B ; S. Karaman, and L. Moeller for LT-B maize technical consultation ; and P. Dixon for assistance with statistical analysis.

Funding was provided by the Iowa State University Plant Sciences Institute through its Biopharmaceuticals Research Initiative.

The authors declare they have no competing financial interests.

Received 6 September 2006 ; accepted 19 December 2006.