Development of a Genetically–Engineered, Candidate Polio Vaccine Employing the Self–Assembling Properties of the Tobacco Mosaic Virus Coat Protein

Haynes, Joel R.; Cunningham, Janet; Seefried, Adolph von; Lennick, Michael; Garvin, Robert T.; Shen, Shi-Hsiang

doi:10.1038/nbt0786-637

Cited by 71 publications

(45 citation statements)

References 23 publications

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“…Pseudovirus particles were created by adding coat protein in vitro to heterologous RNAs that were linked genetically to the TMV origin-of-assembly nucleotide sequence (Sleat et al 1986). The ¢rst indication that plant viruses might carry' foreign sequences and retain biological activity came when Haynes et al (1986), at Connaught Laboratories Ltd, genetically embedded a poliovirus epitope into the TMVCP and assembled particles with and without genomic RNA using recombinant protein made in Escherichia coli. The principle that chimeric virus particles had potential as protective immunogens was thus established with TMV, as well as with the more commonly known hepatitis B surface antigen particles (Valenzuela et al 1985).…”

Section: A Historical Overviewmentioning

confidence: 99%

Tobacco mosaic virus and the virescence of biotechnology

Turpen¹

1999

Phil. Trans. R. Soc. Lond. B

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There is a growing realization that a modern combination of molecular biology and agriculture will provide a photosynthetic basis for the biosynthesis of an increasing variety of complex and valuable molecules. This`greening' of biotechnology may impact on the global environment in many bene¢cial ways, but will perhaps have its most signi¢cant impact on human health. In the past decade, the capacity to use plants as an expanded source of therapeutics has grown through the accelerated development of e¡ective viral transfection vectors for gene transfer to cultivated crops. Recombinant vectors based on tobacco mosaic virus (TMV) and other members of the Tobamovirus genus are now used to transfect commercially meaningful quantities of plant biomass cultivated in enclosed greenhouses and multiacre ¢elds. Viral RNA promoters are e¡ectively manipulated for the synthesis of recombinant messenger RNAs in whole plants. Chimeric plant virus and virus-like particles are designed for peptide production and display from recombinant structural protein^gene fusions. Gene functions are assessed and modi¢ed by either virus-mediated expression or cytosolic inhibition of expression at the RNA level. Recombinant virus populations, propagated by inoculating plants with infectious RNA transcripts or recombinant virions, have proved to be genetically stable over product-manufacturing cycles. Large volumes of highly puri¢ed protein products isolated from transfected foliage conform reproducibly to the speci¢cations required for well-characterized biologics. In some cases, they exceed the speci¢c activities of molecules puri¢ed from alternative recombinant and native sources. The resulting products are then formulated according to the developing national regulatory guidelines appropriate for agriculture-based manufacturing. Each of these innovations was ¢rst realized by researchers using clones of tobamovirus genes and recombinant genomes. This progress is founded on the heritage of a century of fundamental TMV research.

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Section: A Historical Overviewmentioning

confidence: 99%

Tobacco mosaic virus and the virescence of biotechnology

Turpen¹

1999

Phil. Trans. R. Soc. Lond. B

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“…It has been reported that the immunogenicity of these peptides is increased by the use of epitope-presentation systems (10,14). Engineering virus coat proteins to function as carrier molecules for immunogenic peptides has been one of the approaches exploited (18). These carrier proteins have the potential to assemble and form recombinant virus particles displaying the desired epitopes on their surfaces.…”

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confidence: 99%

Identification of Immunogenic Hot Spots within Plum Pox Potyvirus Capsid Protein for Efficient Antigen Presentation

Fernández-Fernández

Martı́nez-Torrecuadrada

Roncal

et al. 2002

J Virol

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“…Several plant viruses have been developed for use as vectors for the expression and delivery of foreign peptides (1)(2)(3)(4)(5)(6)(7). These examples include immunogenic epitopes that can be used in vaccines to confer protective immunity against human and animal diseases.…”

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confidence: 99%

Protective immunity against murine hepatitis virus (MHV) induced by intranasal or subcutaneous administration of hybrids of tobacco mosaic virus that carries an MHV epitope

Koo

Bendahmane

Lettieri

et al. 1999

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

124

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Hybrids of tobacco mosaic virus (TMV) were constructed with the use of fusion to the coat protein peptides of 10 or 15 amino acids, containing the 5B19 epitope from the spike protein of murine hepatitis virus (MHV) and giving rise to TMV-5B19 and TMV-5B19L, respectively. The TMV hybrids were propagated in tobacco plants, and the virus particles were purified. Immunogold labeling, with the use of the monoclonal MAb5B19 antibody, showed specific decoration of hybrid TMV particles, confirming the expression and display of the MHV epitope on the surface of the TMV. Mice were immunized with purified hybrid viruses after several regimens of immunization. Mice that received TMV-5B19L intranasally developed serum IgG and IgA specific for the 5B19 epitope and for the TMV coat protein. Hybrid TMV-5B19, administered by subcutaneous injections, elicited high titers of serum IgG that was specific for the 5B19 epitope and for coat protein, but IgA that was specific against 5B19 was not observed. Mice that were immunized with hybrid virus by subcutaneous or intranasal routes of administration survived challenge with a lethal dose (10 ؋ LD 50 ) of MHV strain JHM, whereas mice administered wild-type TMV died 10 d post challenge. Furthermore, there was a positive correlation between the dose of administered immunogen and protection against MHV infection. These studies show that TMV can be an effective vaccine delivery vehicle for parenteral and mucosal immunization and for protection from challenge with viral infection.Several plant viruses have been developed for use as vectors for the expression and delivery of foreign peptides (1-7). These examples include immunogenic epitopes that can be used in vaccines to confer protective immunity against human and animal diseases. We have demonstrated that a hybrid tobacco mosaic virus (TMV), containing the 13 amino acid sequence of the murine zona pellucida ZP3 epitope fused to a region near the C terminus of the coat protein (CP) successfully elicited the production of anti-ZP3 antibody in parenterally immunized animals. Anti-ZP3 antibody accumulated around the ova of immunized animals; however, it did not prevent fertilization (5).Murine hepatitis virus (MHV), a member of the Coronaviridae family, is responsible for a variety of acute and chronic diseases in its natural host. The strain JHM of MHV induces demyelinating encephalomyelitis with high mortality, and surviving mice exhibit chronic demyelination. MHV contains at least three dominant structural proteins: the membrane glycoprotein (M protein), the nucleocapsid protein (N protein), and the spike glycoprotein (S protein) (8). The S protein is posttranslationally processed to yield the S1 and the S2 proteins (9). The S protein has been the focus of many studies because of its important role in viral attachment to target cellular receptors (10), its membrane penetration, and its ability to induce cell fusion (11). The S protein is a critical determinant of viral pathogenicity and has been shown to contain major immunodomina...

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Development of a Genetically–Engineered, Candidate Polio Vaccine Employing the Self–Assembling Properties of the Tobacco Mosaic Virus Coat Protein

Cited by 71 publications

References 23 publications

Tobacco mosaic virus and the virescence of biotechnology

Tobacco mosaic virus and the virescence of biotechnology

Identification of Immunogenic Hot Spots within Plum Pox Potyvirus Capsid Protein for Efficient Antigen Presentation

Protective immunity against murine hepatitis virus (MHV) induced by intranasal or subcutaneous administration of hybrids of tobacco mosaic virus that carries an MHV epitope

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