Plant made anti-HIV microbicides—A field of opportunity

Stark, Therese; Rybicki, Edward P.; Chikwamba, Rachel

doi:10.1016/j.biotechadv.2012.06.002

Cited by 14 publications

(12 citation statements)

References 169 publications

(206 reference statements)

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“…Technoeconomic evaluation in tobacco, maize and rice has shown that upstream production costs can be reduced to 5% of the cost of fermentation, mainly because plants can be grown in greenhouses that do not need to be GMP ready (Tus e et al, 2014). Although pioneering work has been carried out using tobacco, cereal seeds are likely to be the most suitable platform for deployment in such areas because the infrastructure for large-scale cultivation and harvesting is already in place and the dry seeds favour product stability (Lotter-Stark et al, 2012;Ramessar et al, 2008c). Cereal seeds also have GRAS status which means that crude seed extracts containing antibodies could be used to produce microbicides, removing the need for downstream processing which accounts for up to 80% of overall production costs in plants, and this minimal processing concept has already been demonstrated for other proteins Xie et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Rice endosperm produces an underglycosylated and potent form of the HIV‐neutralizing monoclonal antibody 2G12

Vamvaka

Twyman

Murad

et al. 2015

Plant Biotechnology Journal

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SummaryProtein microbicides against HIV can help to prevent infection but they are required in large, repetitive doses. This makes current fermenter-based production systems prohibitively expensive. Plants are advantageous as production platforms because they offer a safe, economical and scalable alternative, and cereals such as rice are particularly attractive because they could allow pharmaceutical proteins to be produced economically and on a large scale in developing countries. Pharmaceutical proteins can also be stored as unprocessed seed, circumventing the need for a cold chain. Here, we report the development of transgenic rice plants expressing the HIV-neutralizing antibody 2G12 in the endosperm. Surprisingly for an antibody expressed in plants, the heavy chain was predominantly aglycosylated. Nevertheless, the heavy and light chains assembled into functional antibodies with more potent HIV-neutralizing activity than other plant-derived forms of 2G12 bearing typical high-mannose or plant complex-type glycans. Immunolocalization experiments showed that the assembled antibody accumulated predominantly in protein storage vacuoles but also induced the formation of novel, spherical storage compartments surrounded by ribosomes indicating that they originated from the endoplasmic reticulum. The comparison of wild-type and transgenic plants at the transcriptomic and proteomic levels indicated that endogenous genes related to starch biosynthesis were downregulated in the endosperm of the transgenic plants, whereas genes encoding prolamin and glutaredoxin-C8 were up-regulated. Our data provide insight into factors that affect the functional efficacy of neutralizing antibodies in plants and the impact of recombinant proteins on endogenous gene expression.

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Section: Introductionmentioning

confidence: 99%

Rice endosperm produces an underglycosylated and potent form of the HIV‐neutralizing monoclonal antibody 2G12

Vamvaka

Twyman

Murad

et al. 2015

Plant Biotechnology Journal

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“…Antibodies can also be produced in insect cells transfected with baculoviruses expressing the antibody genes, although complex glycosylation is largely absent. Transgenic plants have great potential for antibody production as they can express very large amounts of IgGs, however, the purification processes are currently extensive and costly 34 …”

Section: Antibody Production By Prokaryotes and Eukaryotesmentioning

confidence: 99%

“…HIV antibodies have been produced by a range of different organisms, such as an anti‐capsid Fab produced by E. coli , 86 anti‐gp41 antibodies produced by various insect cells lines 87 and an scFvFc produced by mammalian CHO cells 88 . Numerous HIV antibodies have been produced in transgenic plants such as maize, Arabidopsis and tobacco, but few have been progressed to clinical trials 34 . MAPP66 (a mix of antibodies that includes an anti‐CCR5 to inhibit HIV infection) produced by Nicotinia Benthamiana crops is currently being trialled for the prevention of HIV and Herpes infection as a topical microbicide (http://www.bumc.bu.edu/ipcp/projects/).…”

Section: Development and Production Of Hiv Antibodies In Vitromentioning

confidence: 99%

“…Transgenic plants have great potential for antibody production as they can express very large amounts of IgGs, however, the purification processes are currently extensive and costly. 34 Recombinant antibodies can also be expressed in E. coli and other gram-negative bacteria at high yields. 21 E. coli are capable of making a number of antibody formats, such as scFvs, Fabs and full IgGs, but antibodies produced in E. coli lack glycosylation.…”

Section: Nanobodiesmentioning

confidence: 99%

“…88 Numerous HIV antibodies have been produced in transgenic plants such as maize, Arabidopsis and tobacco, but few have been progressed to clinical trials. 34 MAPP66 (a mix of antibodies that includes an anti-CCR5 to inhibit HIV infection) produced by Nicotinia Benthamiana crops is currently being trialled for the prevention of HIV and Herpes infection as a topical microbicide (www.bumc.bu.edu/ipcp/projects/). One innovative and inexpensive example of HIV antibody production uses bovine colostrum.…”

Section: Development and Production Of Hiv Antibodies In Vitromentioning

confidence: 99%

See 2 more Smart Citations

The maturation of antibody technology for the HIV epidemic

Winnall

Beasley²,

Parsons

et al. 2014

Immunol Cell Biol

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Antibodies are one of our most useful biological tools. Indeed, improvements in antibody‐based technologies have ushered in a new era of antibody‐based therapeutics, research and diagnostic tools. Although improved technologies have led to the development of therapeutic antibodies for treatment of malignancies and inflammatory conditions, the use of advanced antibody technology in the therapy of viral infections is in its infancy. Non‐human primate studies have demonstrated that antibodies against the HIV envelope can both prevent viral infection and control viremia. Despite the obvious potential of antibody therapies against HIV, there remain limitations in production and purification capacity that require further research. Recent advances in recombinant antibody technology have led to the development of a range of novel antibody fragments, such as single‐domain nanobodies and bispecific antibodies, that are capable of targeting cancer cells to cytotoxic T cells. Novel antibody production techniques have also been designed, allowing antibodies to be obtained from non‐mammalian cells, bovine colostrum and the periplasm and cytoplasm of bacteria. These advances may allow large‐scale production of HIV antibodies that are capable of protecting against HIV infection or serving as therapeutics that reduce the need for life‐long antiretroviral treatment. This review summarises recent advances in antibody‐based technologies and discusses the possibilities and challenges of using these advances to design prophylactics and therapeutics against HIV.

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Plant‐derived pharmaceuticals for the developing world

Hefferon

2013

Biotechnology Journal

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Plant-produced vaccines and therapeutic agents offer enormous potential for providing relief to developing countries by reducing the incidence of infant mortality caused by infectious diseases. Vaccines derived from plants have been demonstrated to effectively elicit an immune response. Biopharmaceuticals produced in plants are inexpensive to produce, require fewer expensive purification steps, and can be stored at ambient temperatures for prolonged periods of time. As a result, plant-produced biopharmaceuticals have the potential to be more accessible to the rural poor. This review describes current progress with respect to plant-produced biopharmaceuticals, with a particular emphasis on those that target developing countries. Specific emphasis is given to recent research on the production of plant-produced vaccines toward human immunodeficiency virus, malaria, tuberculosis, hepatitis B virus, Ebola virus, human papillomavirus, rabies virus and common diarrheal diseases. Production platforms used to express vaccines in plants, including nuclear and chloroplast transformation, and the use of viral expression vectors, are described in this review. The review concludes by outlining the next steps for plant-produced vaccines to achieve their goal of providing safe, efficacious and inexpensive vaccines to the developing world.

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Plant made anti-HIV microbicides—A field of opportunity

Cited by 14 publications

References 169 publications

Rice endosperm produces an underglycosylated and potent form of the HIV‐neutralizing monoclonal antibody 2G12

Rice endosperm produces an underglycosylated and potent form of the HIV‐neutralizing monoclonal antibody 2G12

The maturation of antibody technology for the HIV epidemic

Plant‐derived pharmaceuticals for the developing world

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