Cry1Ab has immunogenic as well as allergenic potential
Tests in mice show that the protein in the most commonly grown GM Bt maize may be an allergen when exposure occurs through inhalation.
The mice were exposed to Cry1Ab proteins extracted from their natural source – soil bacteria – and to Cry1Ab-containing MON810 plant materials via inhalation through the nose.
No immune response was found in mice exposed by inhalation to the MON810 pollen or leaf extract, at the doses used. However, exposure to purified Cry1Ab did result in immune and allergic-type responses.
Nevertheless, mice exposed to the plant materials received a considerably lower dose of Cry proteins compared to those exposed to purified protein solutions. This could explain the lack of immune response against the plant Cry1Ab. On the other hand, immunisation with low doses of allergens has been shown to induce more severe allergic responses than high doses, a finding that does not support a simple linear dose–response relationship.
Taken together, the results show that Cry1Ab has immunogenic as well as allergenic potential.
The findings are in agreement with previous investigations showing immunogenic responses after Cry1Ab administration through other routes.
This is thought to be the first time that allergen-specific antibodies have been reported in the blood of Cry1Ab-exposed individuals.
One limitation of the study is that the sporadic exposures did not reflect real-world situations, in which humans, domestic and wild animals are exposed 24/7 for extended periods of time, with simultaneous exposure to a varying number of other foreign substances. So Cry1Ab may be more allergenic and immunotoxic than this study suggests.
The authors concluded:
"Although no Cry protein immunogenicity could be observed at the present dose of MON810 pollen or leaf extract, the specific antibody response against the purified Cry1Ab protoxin and toxin preparations demonstrates the principle that these proteins may affect the immune system, i.e. act as immunogens, after intranasal administration. The elicitation of specific IgE antibodies indicates allergenicity of the purified Cry1Ab proteins. However, this was not observed after exposure to (lower doses of) Cry1Ab in plant materials. Notably, the observed immune responses were elicited in the absence of an adjuvant. Given the importance of Bt-transgenic maize as food and feed across the world, a considerable number of individuals may be exposed to Cry1Ab by inhalation, in the field as well as along the food/feed chain. Thus, our results warrant further clarification and testing, both in animal models and in humans, including emphasis on vulnerable age groups and hypersensitive individuals."
Humoral and cellular immune responses in mice after airway administration of Bacillus thuringiensis Cry1Ab and MON810 cry1Ab-transgenic maize
Monica Andreassen, Elena Rocca, Thomas Bøhn, Odd-Gunnar Wikmark, Johnnie van den Berg, Martinus Løvik, Terje Traavik & Unni Cecilie Nygaard (2014). Food and Agricultural Immunology, DOI: 10.1080/09540105.2014.988128
Genetically modified (GM) crops may bring new proteins with immunogenic and allergenic properties into the food and feed chains. The most commonly grown GM maize, MON810, expresses a modified version of the insecticidal Cry1Ab protein originating in the soil bacterium Bacillus thuringiensis (Bt). Immune reactions following inhalation of pollen and debris from such plants have been scarcely studied. We exposed BALB/c mice to purified Cry1Ab proteins and Cry1Ab-containing MON810 plant materials by intranasal installation. No anti-Cry1Ab antibodies were detected following exposure to the plant materials. Exposure to purified Cry1Ab resulted in specific anti-Cry1Ab IgG1 and IgE production, indicating inherent immunogenicity and allergenicity. Mice exposed to leaf extracts from both MON810 and unmodified maize demonstrated influx of lymphocytes and eosinophils in the broncho-alveolar lavage, and increased cytokine release in mediastinal lymph node cells. The results indicate that the airway exposure to Cry1Ab proteins may be a route of practical relevance.