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      Use of macromolecular assemblies as expression systems for peptides and synthetic vaccines

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          Abstract

          The past decade has witnessed the development of numerous systems for the presentation of antigens on the surface of self-assembling macromolecules. Although the sites for insertion were initially chosen empirically, the determination of the three-dimensional structures of a number of carrier macromolecules has enabled structure-based insertional mutagenesis to be used increasingly. Furthermore, it is now feasible to determine the structure of an inserted sequence as presented in a heterologous environment, making it possible to correlate the detailed structure of a peptide with its immunological properties.

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          Most cited references63

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          Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface.

          G. Smith (1985)
          Foreign DNA fragments can be inserted into filamentous phage gene III to create a fusion protein with the foreign sequence in the middle. The fusion protein is incorporated into the virion, which retains infectivity and displays the foreign amino acids in immunologically accessible form. These "fusion phage" can be enriched more than 1000-fold over ordinary phage by affinity for antibody directed against the foreign sequence. Fusion phage may provide a simple way of cloning a gene when an antibody against the product of that gene is available.
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            The three-dimensional structure of the bacterial virus MS2.

            The structure of the icosahedral bacteriophage MS2 has been determined to 3.3 A resolution by X-ray crystallography. The phase determination involved both molecular replacement at low resolution using a known structure and heavy-atom substitution. The coat protein has no structural similarity to that of any other known RNA virus.
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              Development of cowpea mosaic virus as a high-yielding system for the presentation of foreign peptides.

              It has recently been shown that cowpea plants can be infected with a cowpea mosaic virus (CPMV) chimera containing an antigenic site from foot-and-mouth disease virus (Usha et al., Virology 197, 366-374, 1993). Analysis of progeny RNA produced during such an infection has revealed that the inserted sequence is rapidly lost during serial passaging, probably by a process of homologous recombination. Using the information gained from this analysis, we have redesigned the chimeras in such a way that they are now genetically stable. The modified constructs have been used to obtain large quantities of purified virus particles expressing epitopes derived from human rhinovirus 14 (HRV-14) and human immunodeficiency virus type 1 (HIV-1). The chimeric virus particles possess the antigenic properties of the inserted sequence and, in the case of the HRV-14-derived construct, it has been shown that the inserted epitope is immunogenic in rabbits. These results demonstrate that CPMV can be used as a high-yielding system for the presentation of foreign peptide sequences.
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                Author and article information

                Contributors
                Journal
                Curr Opin Struct Biol
                Curr. Opin. Struct. Biol
                Current Opinion in Structural Biology
                Published by Elsevier Ltd.
                0959-440X
                1879-033X
                11 February 2002
                April 1996
                11 February 2002
                : 6
                : 2
                : 176-182
                Affiliations
                [a ]Department of Virus Research, John Innes Centre, Colney Lane, Norwich NR4 7UH, UK
                [b ]Department of Molecular Biology, The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, California 92037, USA
                Article
                S0959-440X(96)80072-8
                10.1016/S0959-440X(96)80072-8
                7133382
                8728650
                9e4a4bac-137a-4f79-ba33-ed72d6795909
                Copyright © 1996 Published by Elsevier Ltd.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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                Biophysics
                clp core-like particle,cpmv cowpea mosaic virus,3d three-dimensional,fmdv foot and mouth disease virus,hrv14 human rhinovirus 14,hsv1 herpes simplex virus type 1,mhv mouse hepatitis virus,pvx potato virus x,tmv tobacco mosaic virus,vp virus protein

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