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

BMC Biotechnology

Research Article

Ewa Szolajska¹  Malgorzata Podsiadla¹  Antonina Naskalska¹  Jadwiga Chroboczek²  Igor Andreev³ 

[1] Institute of Biochemistry and Biophysics, PAS, Pawinskiego 5a, 02106, Warsaw, Poland;Institute of Biochemistry and Biophysics, PAS, Pawinskiego 5a, 02106, Warsaw, Poland;Therex/TIMC/IMAG, UJF-CNRS, UMR 5525, Domaine de la Merci, 38706, La Tronche, France;Institute of Molecular Biology and Genetics, NASU, 150 Zabolotny Str. 143, Kiev, Ukraine;

关键词: Influenza vaccine;    Hemagglutinin;    Adenovirus dodecahedron;    WW-domain adaptor;    Vaccine presentation platform;    Multivalency;   

DOI  :  10.1186/1472-6750-13-50

 received in 2012-11-26, accepted in 2013-06-05,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundThe 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.ResultsSince 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.ConclusionsEngineering of a soluble complex of HA with Dd, a virus-like particle that serves as a vector, an adjuvant and as a multivalent presentation platform, is an important step toward a novel influenza vaccine.

【 授权许可】

Unknown   
© Naskalska et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.