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. © 2009 Portland Press Ltd.

Dengue-4 envelope domain III fused twice within the meningococcal P64k protein carrier induces partial protection in mice / L. Lazo, A. Zulueta, L. Hermida, A. Blanco, J. Sánchez, I. Valdés, L. Gil, C. López, Y. Romero, M.G. Guzmán, G. Guillén. - In: BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY. - ISSN 0885-4513. - 52:4(2009), pp. 265-271.

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

ZULUETA MORALES, AIDA;
2009

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. © 2009 Portland Press Ltd.
Dengue-4 envelope domain III; Flavivirus; Meningococcal p64k protein carrier; Vaccine; Animals; Bacterial Outer Membrane Proteins; Dengue; Dengue Vaccines; Female; Mice; Mice, Inbred BALB C; Recombinant Fusion Proteins; Treatment Outcome; Viral Envelope Proteins; Drug Discovery3003 Pharmaceutical Science; Applied Microbiology and Biotechnology; Biomedical Engineering; Process Chemistry and Technology; Bioengineering; Molecular Medicine; Biotechnology
Settore BIO/10 - Biochimica
Settore BIO/11 - Biologia Molecolare
Settore BIO/19 - Microbiologia Generale
BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY
http://www.babonline.org/bab/052/0265/0520265.pdf
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/491434
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