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


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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    • "The plant-made vaccine field started two decades ago with the promise of developing low-cost vaccines to prevent infectious disease outbreaks and epidemics around the globe, but this goal has not yet been realized. A few clinical trials have been conducted a decade ago using lettuce leaves (Kapusta et al., 1999), maize seeds (Tacket et al., 2004) and potato tubers (Tacket et al., 1998, 2000; Thanavala et al., 2005) expressing different vaccines antigens. However, none of them advanced beyond phase I clinical trial or result in any licensed product. "
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    ABSTRACT: Although the plant-made vaccine field started three decades ago with the promise of developing low-cost vaccines to prevent infectious disease outbreaks and epidemics around the globe, this goal has not yet been achieved. Plants offer several major advantages in vaccine generation, including low-cost production by eliminating expensive fermentation and purification systems, sterile delivery and cold storage/transportation. Most importantly, oral vaccination using plant-made antigens confers both mucosal (IgA) and systemic (IgG) immunity. Studies in the past 5 years have made significant progress in expressing vaccine antigens in edible leaves (especially lettuce), processing leaves or seeds through lyophilization and achieving antigen stability and efficacy after prolonged storage at ambient temperatures. Bioencapsulation of antigens in plant cells protects them from the digestive system; the fusion of antigens to transmucosal carriers enhances efficiency of their delivery to the immune system and facilitates successful development of plant vaccines as oral boosters. However, the lack of oral priming approaches diminishes these advantages because purified antigens, cold storage/transportation and limited shelf life are still major challenges for priming with adjuvants and for antigen delivery by injection. Yet another challenge is the risk of inducing tolerance without priming the host immune system. Therefore, mechanistic aspects of these two opposing processes (antibody production or suppression) are discussed in this review. In addition, we summarize recent progress made in oral delivery of vaccine antigens expressed in plant cells via the chloroplast or nuclear genomes and potential challenges in achieving immunity against infectious diseases using cold-chain-free vaccine delivery approaches.
    Plant Biotechnology Journal 09/2015; 13(8). DOI:10.1111/pbi.12471 · 5.75 Impact Factor
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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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