Edible plant vaccines: applications for prophylactic and therapeutic molecular medicine

Mason, Hugh S.; Warzecha, Heribert; Mor, Tsafrir S.; Arntzen, Charles J.

doi:10.1016/s1471-4914(02)02360-2

Cited by 207 publications

(124 citation statements)

References 39 publications

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“…Genetically modified chloroplast genomes of most crops are maternally inherited, and the absence of any reproductive structures offers efficient foreign gene containment (38,39) and therefore facilitates their safe production in the field (23). Plant cells provide bioencapsulation and protect therapeutic proteins from degradation in the stomach from acids and enzymes (30). Plants also reduce concerns about pathogen contamination as may be the case for production of proteins in transgenic animals.…”

Section: Discussionmentioning

confidence: 99%

Oral delivery of bioencapsulated coagulation factor IX prevents inhibitor formation and fatal anaphylaxis in hemophilia B mice

Verma

Moeini

LoDuca

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

135

207

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To address complications of pathogenic antibody or life-threatening anaphylactic reactions in protein replacement therapy for patients with hemophilia or other inherited protein deficiencies, we have developed a prophylactic protocol using a murine hemophilia B model. Oral delivery of coagulation factor IX fused with cholera toxin β-subunit (with or without a furin cleavage site; CTB-FFIX or CTB-FIX), expressed in chloroplasts (up to 3.8% soluble protein or 0.4 mg/g leaf tissue), bioencapsulated in plant cells, effectively blocked formation of inhibitory antibodies (undetectable or up to 100-fold less than controls). Moreover, this treatment eliminated fatal anaphylactic reactions that occurred after four to six exposures to intravenous F.IX. Whereas only 20-25% of control animals survived after six to eight F.IX doses, 90-93% of F.IX-fed mice survived 12 injections without signs of allergy or anaphylaxis. Immunostaining confirmed delivery of F.IX to Peyer's patches in the ileum. Within 2-5 h, feeding of CTB-FFIX additionally resulted in systemic delivery of F.IX antigen. This high-responder strain of hemophilia B mice represents a new animal model to study anaphylactic reactions. The protocol was effective over a range of oral antigen doses (equivalent to 5-80 μg recombinant F.IX/kg), and controlled inhibitor formation and anaphylaxis long-term, up to 7 months (∼40% life span of this mouse strain). Oral antigen administration caused a deviant immune response that suppressed formation of IgE and inhibitory antibodies. This cost-effective and efficient approach of antigen delivery to the gut should be applicable to several genetic diseases that are prone to pathogenic antibody responses during treatment.allergy | chloroplast | genetic disorders | oral tolerance | plant-made therapeutics

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Section: Discussionmentioning

confidence: 99%

Oral delivery of bioencapsulated coagulation factor IX prevents inhibitor formation and fatal anaphylaxis in hemophilia B mice

Verma

Moeini

LoDuca

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

135

207

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“…Here, we explore the potential of a chimeric protein comprised of the P1 peptide fused to the G M1 -ganglioside-binding B subunit of the cholera toxin (CTB) to fulfill the requirements of contextual integrity of this gp41 domain, mucosal targeting, and immunogenicity. Our approach combines a mucosally targeted immunogen, CTB-P1, with an unique production system, namely transgenic plants (29)(30)(31)(32), that may enable the creation of safe, effective, needlefree, and lower cost recombinant HIV-1 vaccines.…”

mentioning

confidence: 99%

A mucosally targeted subunit vaccine candidate eliciting HIV-1 transcytosis-blocking Abs

Matoba

Magérus

Geyer

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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A vaccine that would engage the mucosal immune system against a broad range of HIV-1 subtypes and prevent epithelial transmission is highly desirable. Here we report fusing the mucosal targeting B subunit of cholera toxin to the conserved galactosylceramide-binding domain (including the ELDKWA-neutralizing epitope) of the HIV-1 gp41 envelope protein, which mediates the transcytosis of HIV-1 across the mucosal epithelia. Chimeric protein expressed in bacteria or plants assembled into oligomers that were capable of binding galactosyl-ceramide and G M1 gangliosides. Mucosal (intranasal) administration in mice of the purified chimeric protein followed by an i.p. boost resulted in transcytosis-neutralizing serum IgG and mucosal IgA responses and induced immunological memory. Plant production of mucosally targeted immunogens could be particularly useful for immunization programs in developing countries, where desirable product traits include low cost of manufacture, heat stability, and needle-free delivery.

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“…Therefore, over-accumulation of unphysiological concentrations of ARF protein alone should be capable of stimulating the secretion processes without artificial manipulation of the ARF-regulators in plant cells. Recently, many attempts have been made to employ higher plant cells as a chamber for mass production of useful biological polymers, 21,22) such as antibodies, vaccines and cytokines. If translatable region(s) of appropriate gene(s) encoding ARF proteins (usually about 500-600 bp) can be co-expressed together with desired genes, this could activate the secretion of the products into culture medium.…”

Section: Biochemical Properties Of Transformed Belladonnamentioning

confidence: 99%

Enhanced Secretory Activity of Atropa belladonna Hairy Root Culture Over-expressing ADP-Ribosylation Factor Gene

Asakura

Seki

Muranaka

et al. 2008

Biological & Pharmaceutical Bulletin

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Monomeric GTP-binding proteins are involved in regulating numerous essential functions of eukaryotic cells, such as cell differentiation, intracellular vesicle transport, and cytoskeleton organization. [1][2][3][4][5] Based on the amino acid homology and the deduced functions, the low molecular weight GTP-binding proteins are generally classified into several families. 2,5) It has been well known 3,4) that activation of these small GTP-binding proteins is strictly controlled by the two regulatory proteins, GDP/GTP exchanging factor (GEF) and the GTPase-activating protein (GAP). GEP interacts with inactive small G-proteins to covert them to GTP-bound active form, while small G-protein-GTP complex is changed to the inactive form by the hydrolysis of GTP to GDP by the action of GTPase-activating protein (GAP). ADP-ribosylation factor (ARF) is a member of the Arf/Sar family of small G-proteins, 1,4) and several lines of evidence suggest that these proteins function in vesicular transport from endoplasmic reticulum to the plasma membrane via the Golgi apparatus.6,7) As well as other small G-proteins, the functions of this class of are regulated by ARF-specific GEF and GAP. It has been demonstrated 8) that over-expression of ARF-specific GEF restores the inhibitor-induced defect of secretory activity. On the other hand, it has been recently shown 9) that over-expression of ARF-specific GAP appreciably inhibits the proteintrafficking processes from the endoplasmic reticulum to Golgi apparatus. Therefore, the effects of unphysiologically high concentrations of the two ARF-regulator proteins GEF and GAP have been examined in detail. In contrast, however, only very limited information is available on the biochemical properties of the transformed cells over-expressing ARF protein itself.We have reported previously 10) that genes encoding ARF proteins of carrot are organized as a small or multi-gene family in the genome, and arf-001 (GeneBank accession no. AY874441) has been isolated as a carrot ARF gene. The primary amino acid sequence of arf-001 appears to show significant homology to ARF proteins from various biological sources. In order to understand the physiological functions and effects of over-accumulation of the products of ARF genes in higher plant cells, in the present experiments, we attempted to prepare the transformed cells of Atropa belladonna over-expressing carrot arf-001. The newly developed vectors, pBCR82 and pBCR90, have been employed for over-expression of arf-001 and as the empty vector control, respectively, 11) and the transformed cells were obtained as hairy root tissues by co-expression of rol cluster in these vectors. MATERIALS AND METHODS MaterialsSeeds of A. belladonna L. were surface-sterilized in 70% (v/v) ethanol and 2% (v/v) sodium hypochlorite, successively, and, after several washings with autoclaved water, they were placed on Murashige and Skoog's agar medium 12) for germination. The sterilized seeds were then incubated at 26°C under constant illumination for germination, and the leaf se...

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Edible plant vaccines: applications for prophylactic and therapeutic molecular medicine

Cited by 207 publications

References 39 publications

Oral delivery of bioencapsulated coagulation factor IX prevents inhibitor formation and fatal anaphylaxis in hemophilia B mice

Oral delivery of bioencapsulated coagulation factor IX prevents inhibitor formation and fatal anaphylaxis in hemophilia B mice

A mucosally targeted subunit vaccine candidate eliciting HIV-1 transcytosis-blocking Abs

Enhanced Secretory Activity of Atropa belladonna Hairy Root Culture Over-expressing ADP-Ribosylation Factor Gene

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