Document Detail


Analysis of a recombinant dengue-2 virus-dengue-3 virus hybrid envelope protein expressed in a secretory baculovirus system.
MedLine Citation:
PMID:  9367357     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
H Bielefeldt-Ohmann; D W Beasley; D R Fitzpatrick; J G Aaskov
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of general virology     Volume:  78 ( Pt 11)     ISSN:  0022-1317     ISO Abbreviation:  J. Gen. Virol.     Publication Date:  1997 Nov 
Date Detail:
Created Date:  1997-12-08     Completed Date:  1997-12-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0077340     Medline TA:  J Gen Virol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  2723-33     Citation Subset:  IM    
Affiliation:
Centre for Molecular Biotechnology, School of Life Science, Queensland University of Technology, Brisbane, Australia. helle@biosci.uq.edu.au
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MeSH Terms
Descriptor/Qualifier:
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:
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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