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Towards a novel influenza vaccine: engineering of hemagglutinin on a platform of adenovirus dodecahedron

Naskalska, Antonina and Szolajska, Ewa and Andreev, Igor and Podsiadla, Malgorzata and Chroboczek, Jadwiga (2013) Towards a novel influenza vaccine: engineering of hemagglutinin on a platform of adenovirus dodecahedron. BMC Biotechnology, 13 . 50..



Background: The production process for the current influenza vaccine takes about 6 months and its antigenic composition must be modified annually. In the attempt towards developing influenza vaccine production that would be faster, safer and cheaper we engineered an influenza vaccine in which multiple copies of hemagglutinin (HA) would be delivered by a vector, adenovirus dodecahedron (Ad Dd). Dd is a virus-like particle, formed by assembly of twelve copies of pentameric penton base (Pb) proteins responsible for virus penetration. In order to attach HA to the vector, an adaptor containing WW domains was used. The WW domain is a linear peptide fragment identified as a partner of proline-proline-x-tyrosine (PPxY) motif present at the N-terminal extremity of the Pb protein, which is a building block of Dd. That tandem of three WW domains in fusion with the protein of interest enables interaction with Dd and efficient translocation to the cytoplasm of cells in culture. Results: Since HA is an oligomeric protein with complicated processing, we prepared six different constructs of HA (A/swan/Poland/467/2006(H5N1)) in fusion with the WW adaptor. Herein we report baculovirus expression and functional analysis of six HA-WW variants. The best behaving variant was successfully delivered into human cells in vitro. Conclusions: Engineering of a soluble complex of HA with Dd, a virus-like particle that serves as a vector, an adjuvantand as a multivalent presentation platform, is an important step toward a novel influenza vaccine. Keywords: Influenza vaccine, Hemagglutinin, Adenovirus dodecahedron, WW-domain adaptor, Vaccine presentation platform, Multivalency

Item Type:Article
Subjects:Q Science > Q Science (General)
Divisions:Department of Protein Biosynthesis
ID Code:581
Deposited By: dr Ewa/E Szolajska
Deposited On:18 Feb 2014 17:04
Last Modified:15 Oct 2014 07:57

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