Immunogenicity of recombinant LT-B delivered orally to humans in transgenic corn. Vaccine

Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201, USA.
Vaccine (Impact Factor: 3.62). 11/2004; 22(31-32):4385-9. DOI: 10.1016/j.vaccine.2004.01.073
Source: PubMed

ABSTRACT Previous clinical studies have demonstrated the feasibility of using edible transgenic plants to deliver protective antigens as new oral vaccines. Transgenic corn is particularly attractive for this purpose since the recombinant antigen is stable and homogeneous, and corn can be formulated in several edible forms without destroying the cloned antigen. Transgenic corn expressing 1 mg of LT-B of Escherichia coli without buffer was fed to adult volunteers in three doses, each consisting of 2.1 g of plant material. Seven (78%) of nine volunteers developed rises in both serum IgG anti-LT and numbers of specific antibody secreting cells after vaccination. Four (44%) of nine volunteers also developed stool IgA. Transgenic plants represent a new vector for oral vaccine antigens.

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    • "Subcellular targeting of the LTB to the vacuole along with the use of a constitutive promoter has increased yield of the LTB for up to 12 % of total soluble protein (TSP). This candidate vaccine has been subsequently delivered as defatted corn germ meal to adult volunteers (Tacket et al. 2004). Seven out of nine volunteers participating in this oral feeding study have elicited an increase in serum IgG anti-heat-labile enterotoxin (LT) following vaccination. "
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    • "Intestinal mucosa represents an attractive target for oral delivery of immunogens and for mucosal vaccination. Several oral strategies, using biodegradable polymeric particles [6] [7], liposome [8], bacterial ghost [9], plant lectins [10] [11], adjuvanted vaccines [12] or transgenic plants [13] [14], have been adopted to protect the antigens in the gastrointestinal tract and to increase uptake by DCs, causing their maturation and their migration to the intrafollicular areas. PLA (poly(lactic acid)) or PLGA (poly(lactic-co-glycolic acid)) nanoparticles are suitable protein carriers offering antigen protection , increased penetration across mucosal surface and controlled release of encapsulated antigen [15]. "
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    ABSTRACT: Peyer's patch have been extensively studied as a major inductive site for mucosal immunity within the small intestine. The intestinal mucosa contains numerous dendritic cells, which induce either protective immunity to infectious agents or tolerance to innocuous antigens, including food and commensal bacteria. Although during the past few years, several subsets of human mucosal dendritic cells have been described, a precise characterization of the different mouse mucosal dendritic cells subpopulations remains to be achieved with regard to their phenotype and localization in Peyer's patch. In this report, we have investigated by immunofluorescence on cryosection and by flow cytometry, the phenotype and the localization of dendritic cells into Peyer's patch of C57Bl/6 mouse intestine using dendritic cells markers. Positive and double staining for CD11c and BDCA-2, pDC/IPC, DC-LAMP, DC-SIGN, TLR8 and Langerin have been observed revealing new mouse intestinal DC subsets. This study provides new insight in the understanding of mucosal immune responses induced by natural processes as infections but also new perspectives for the evaluation of oral vaccines.
    Vaccine 03/2011; 29(20):3655-61. DOI:10.1016/j.vaccine.2011.03.012 · 3.62 Impact Factor
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    • "The expression level of both B subunits, measured by quantitative ELISA, varied between 0.5 and 2.7% of the total soluble protein (TSP), which represents about 1.3 mg/g seed recombinant protein. According to Tacket et al. (2004) this level of protein expression is sufficient to generate a sizeable amount of antigen after the consumption of a few milligrams of seeds, and the transgenic rice lines can be used for the production of rice seed-based edible vaccines. "
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    ABSTRACT: Seed is an ideal protein production platform because it is the storage organ of the plant and offers appropriate storage compartments for the deposition of foreign proteins. To achieve high foreign protein expression level in the endosperm tissue, the transformation cassette carried the tissue-specific promoter of the wheat high-molecularweight glutenin subunit protein 1Bx17, fused to the first intron of rice actin promoter. Transformation protocols were established and optimized in the laboratory for cereals such as rice, barley and wheat using direct DNA delivery and the Agrobacterium tumefaciensmediated transformation system. Both immature (barley) and mature (rice) embryos, and immature inflorescences (wheat) were used as sources of explants. Subunit edible vaccines were produced to introduce the LTB, CTB and fused LTB-PEDV genes into the rice genome. The PEDV gene was also integrated into the barley genome. A project has recently been started to produce a rabbit-derived enzyme in transgenic wheat endosperm to be used by the pharmaceutical industry.
    Acta Agronomica Hungarica 03/2010; 57(1):55-64. DOI:10.1556/AAgr.58.2010.1.7
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