| Analysis of a recombinant dengue-2 virus-dengue-3 virus hybrid envelope protein expressed in a secretory baculovirus system. | |
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MedLine Citation:
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PMID: 9367357 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In a step towards a tetravalent dengue virus subunit vaccine which is economical to produce, highly immunogenic and stable, a hybrid dengue virus envelope (E) protein molecule has been constructed. It consists of 36 amino acids from the membrane protein, the N-terminal 288 amino acids of the dengue-2 virus E protein plus amino acids 289-424 of the dengue-3 virus E protein. It has been engineered for secretory expression by fusion to a mellitin secretory signal sequence and truncation of the hydrophobic transmembrane segment. Using the baculovirus expression system and serum-free conditions, more than 95% of recombinant dengue-2 virus-dengue-3 virus hybrid E protein (rD2D3E) was secreted into the cell culture supernatant in a stable form with multiple features indicative of preserved conformation. The hybrid molecule reacted with a panel of dengue virus- and flavivirus-specific MAbs which recognize linear or conformational epitopes on dengue virions. Human dengue virus-specific antisera also reacted with the protein. The hybrid rD2D3E protein was able to inhibit the in vitro binding of dengue-2 and dengue-3 viruses to human myelomonocytic cells, suggesting that the receptor-binding epitope(s) was preserved. Adjuvant-free immunization with the hybrid protein induced an antibody response to both dengue-2 and dengue-3 virus in outbred mice, comparable in strength to that of individual rD2E and rD3E proteins. Notably, these antibody responses were primarily of the IgG2a and IgG2b isotype. A strong dengue virus cross-reactive T cell response was also induced in the mice, suggesting that dengue virus hybrid E proteins could form the basis of an efficacious multivalent dengue virus vaccine. |
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Authors:
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H Bielefeldt-Ohmann; D W Beasley; D R Fitzpatrick; J G Aaskov |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of general virology Volume: 78 ( Pt 11) ISSN: 0022-1317 ISO Abbreviation: J. Gen. Virol. Publication Date: 1997 Nov |
Date Detail:
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Created Date: 1997-12-08 Completed Date: 1997-12-08 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0077340 Medline TA: J Gen Virol Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 2723-33 Citation Subset: IM |
Affiliation:
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Centre for Molecular Biotechnology, School of Life Science, Queensland University of Technology, Brisbane, Australia. helle@biosci.uq.edu.au |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Baculoviridae / genetics* Dengue Virus / genetics*, immunology, metabolism Humans Mice Protein Engineering Recombinant Fusion Proteins / genetics, metabolism Recombinant Proteins / biosynthesis, genetics T-Lymphocytes / immunology, virology* Viral Envelope Proteins / genetics*, immunology, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Recombinant Fusion Proteins; 0/Recombinant Proteins; 0/Viral Envelope Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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