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Dengue‐4 envelope domain III fused twice within the meningococcal P64k protein carrier induces partial protection in mice

Dengue‐4 envelope domain III fused twice within the meningococcal P64k protein carrier induces... A vaccine against dengue virus must be able to induce an effective and equivalent immune response to the four viral serotypes; however, some studies have revealed that DEN4 (dengue‐virus serotype 4) induces a weaker immune response than the others in quadrivalent (tetravalent’) formulations. We have previously reported the protective capacity, in a viral encephalitis murine model, of fusion protein P64k–envelope domain III of DEN1, DEN2 and DEN3. We also reported that the P64k protein can be used as a carrier in two different positions: the insertion following the first 45 amino acids and the fusion at the C‐terminus. Considering the low immunogenicity described for DEN4, in the present study we obtained a novel chimaeric protein by inserting two dengue‐4 envelope domains III in both sites of P64k (PD24), and hence increasing the presence of the virus in the final construct. After expression in Escherichia coli and semipurification, the protein exhibited a pattern of high molecular mass and was well recognized by human and murine polyclonal antibodies. The protein was finally evaluated in mice, Al(OH)3 being employed as the adjuvant. Even though the animals exhibited low levels of antiviral antibodies, the recombinant protein induced significant protection against lethal challenge with dengue‐4 virus. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Biotechnology and Applied Biochemistry Wiley

Dengue‐4 envelope domain III fused twice within the meningococcal P64k protein carrier induces partial protection in mice

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References (3)

Publisher
Wiley
Copyright
2009 International Union of Biochemistry and Molecular Biology
ISSN
0885-4513
eISSN
1470-8744
DOI
10.1042/BA20080074
pmid
18636968
Publisher site
See Article on Publisher Site

Abstract

A vaccine against dengue virus must be able to induce an effective and equivalent immune response to the four viral serotypes; however, some studies have revealed that DEN4 (dengue‐virus serotype 4) induces a weaker immune response than the others in quadrivalent (tetravalent’) formulations. We have previously reported the protective capacity, in a viral encephalitis murine model, of fusion protein P64k–envelope domain III of DEN1, DEN2 and DEN3. We also reported that the P64k protein can be used as a carrier in two different positions: the insertion following the first 45 amino acids and the fusion at the C‐terminus. Considering the low immunogenicity described for DEN4, in the present study we obtained a novel chimaeric protein by inserting two dengue‐4 envelope domains III in both sites of P64k (PD24), and hence increasing the presence of the virus in the final construct. After expression in Escherichia coli and semipurification, the protein exhibited a pattern of high molecular mass and was well recognized by human and murine polyclonal antibodies. The protein was finally evaluated in mice, Al(OH)3 being employed as the adjuvant. Even though the animals exhibited low levels of antiviral antibodies, the recombinant protein induced significant protection against lethal challenge with dengue‐4 virus.

Journal

Biotechnology and Applied BiochemistryWiley

Published: Apr 1, 2009

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