An avian influenza A
(H7N9) virus vaccine candidate based on the fusion protein of hemagglutinin
globular head and Salmonella typhimurium flagellin
Li Song12, Dan Xiong12, Xilong Kang12, Yun Yang12, Jing
Wang12, Yaxin Guo12, Hui Xu12, Sujuan Chen12, Daxin Peng12, Zhiming Pan12* and
Xinan Jiao12*
* Corresponding authors: Zhiming
Pan zmpan@yzu.edu.cn - Xinan Jiao jiao@yzu.edu.cn
Author Affiliations
1 Jiangsu Co-innovation Center for Prevention and Control of
Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, Jiangsu,
China
2 Jiangsu Key Laboratory of Zoonosis, Yangzhou University,
48 East Wenhui Road, Yangzhou 225009, Jiangsu, China
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BMC Biotechnology 2015, 15:79 doi:10.1186/s12896-015-0195-z
The electronic version of this article is the complete one
and can be found online at: http://www.biomedcentral.com/1472-6750/15/79
Received: 16
March 2015
Accepted: 15 July
2015
Published: 19
August 2015
© 2015 Song et al.
Open Access This article is distributed under the terms of
the Creative Commons Attribution 4.0 International License
(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
distribution, and reproduction in any medium, provided you give appropriate
credit to the original author(s) and the source, provide a link to the Creative
Commons license, and indicate if changes were made. The Creative Commons Public
Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/)
applies to the data made available in this article, unless otherwise stated.
A novel influenza virus, subtype H7N9, circulated through
China in 2013–2014. Its higher rates of human infection in a wide range of
locations within China and the associated increased likelihood of
human-to-human transmission have caused global concern. Recombinant subunit
vaccines provide safe and targeted protection against viral infections.
However, the protective efficacy of recombinant subunit vaccines tends to be
less potent than vaccines made from whole viruses. Studies have shown that
bacterial flagellin has strong adjuvant activity and induces protective immune
responses.
Results In this
study, we used overlap-PCR to generate an H7N9 influenza recombinant subunit
vaccine that fused the globular head domain (HA1-2, aa 62–284) of the
protective hemagglutinin (HA) antigen with the potent TLR5 ligand, Salmonella
typhimurium flagellin (fliC). The resulting fusion protein, HA1-2-fliC, was
efficiently expressed in an Escherichia coli prokaryotic expression system, and
Western blotting and TLR5-stimulating activity analysis confirmed that the
HA1-2-fliC moiety could be faithfully refolded to take on the native HA and
fliC conformations. In a C3H/HeJ mouse model of intraperitoneal vaccination,
the fusion protein elicited significant and robust HA1-2-specific serum IgG
titers, maintaining high levels for at least 3 months in the vaccinated animals,
and induced similar levels of HA1-2-specific IgG1 and IgG2a that were
detectable 12 days after the third immunization. HA1-2-fliC was also found to
be capable of triggering the production of neutralizing antibodies, as assessed
by measuring hemagglutination inhibition titers.
Conclusions We
conclude that immunization with HA1-2-fliC induces potent HA1-2-specific
responses, offering significant promise for the development of a successful
recombinant subunit vaccine for avian influenza A (H7N9). TOMADO DE ENVIO DE BCM
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