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Surface displaying of swine IgG1 Fc enhances baculovirus-vectored vaccine efficacy by facilitating viral complement escape and mammalian cell transduction

Baculovirus-mediated gene transfer has been developed as a vaccine design strategy against a number of diseases without apparent viral replication. However, it has been hampered by complement-dependent inactivation, thus hindering the in vivo application of baculovirus. A variety of approaches have...

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Autores principales: Liu, Zehui, Liu, Yangkun, Zhang, Yuanyuan, Yang, Yajuan, Ren, Jingjing, Zhang, Xiaoying, Du, Enqi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5429525/
https://www.ncbi.nlm.nih.gov/pubmed/28499403
http://dx.doi.org/10.1186/s13567-017-0434-5
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author Liu, Zehui
Liu, Yangkun
Zhang, Yuanyuan
Yang, Yajuan
Ren, Jingjing
Zhang, Xiaoying
Du, Enqi
author_facet Liu, Zehui
Liu, Yangkun
Zhang, Yuanyuan
Yang, Yajuan
Ren, Jingjing
Zhang, Xiaoying
Du, Enqi
author_sort Liu, Zehui
collection PubMed
description Baculovirus-mediated gene transfer has been developed as a vaccine design strategy against a number of diseases without apparent viral replication. However, it has been hampered by complement-dependent inactivation, thus hindering the in vivo application of baculovirus. A variety of approaches have been exploited to bypass the complement system in the serum. In this study, we constructed and screened a series of baculovirus vectors displaying complement interfering factors, of which a baculovirus vector displaying swine IgG1 Fc (pFc) showed the highest complement antagonism (75.6%). Flow cytometry analysis of transduced cells demonstrated that the baculovirus display of pFc had a significant increase in transduction efficiency and transgene expression of reporter genes. On this basis, a VSV-G-pseudotyped with swine IgG1 Fc surface displayed baculovirus vector was developed to express the classical swine fever virus (CSFV) E2 gene. The translational enhancers Syn21 and P10UTR were incorporated to improve the antigen expression. The E2 gene was efficiently expressed in both insect and mammalian cells. Pigs immunized with this recombinant baculovirus developed high levels of E2-specific antibody, CSFV-specific neutralizing antibody and IFN-γ-secreting cellular immune responses. These results demonstrate that the strategy of surface-displaying swine IgG1 Fc has a great potential to improve the efficiency of baculovirus-vectored vaccine for CSFV and other swine pathogens. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-017-0434-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-54295252017-05-15 Surface displaying of swine IgG1 Fc enhances baculovirus-vectored vaccine efficacy by facilitating viral complement escape and mammalian cell transduction Liu, Zehui Liu, Yangkun Zhang, Yuanyuan Yang, Yajuan Ren, Jingjing Zhang, Xiaoying Du, Enqi Vet Res Research Article Baculovirus-mediated gene transfer has been developed as a vaccine design strategy against a number of diseases without apparent viral replication. However, it has been hampered by complement-dependent inactivation, thus hindering the in vivo application of baculovirus. A variety of approaches have been exploited to bypass the complement system in the serum. In this study, we constructed and screened a series of baculovirus vectors displaying complement interfering factors, of which a baculovirus vector displaying swine IgG1 Fc (pFc) showed the highest complement antagonism (75.6%). Flow cytometry analysis of transduced cells demonstrated that the baculovirus display of pFc had a significant increase in transduction efficiency and transgene expression of reporter genes. On this basis, a VSV-G-pseudotyped with swine IgG1 Fc surface displayed baculovirus vector was developed to express the classical swine fever virus (CSFV) E2 gene. The translational enhancers Syn21 and P10UTR were incorporated to improve the antigen expression. The E2 gene was efficiently expressed in both insect and mammalian cells. Pigs immunized with this recombinant baculovirus developed high levels of E2-specific antibody, CSFV-specific neutralizing antibody and IFN-γ-secreting cellular immune responses. These results demonstrate that the strategy of surface-displaying swine IgG1 Fc has a great potential to improve the efficiency of baculovirus-vectored vaccine for CSFV and other swine pathogens. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-017-0434-5) contains supplementary material, which is available to authorized users. BioMed Central 2017-05-12 2017 /pmc/articles/PMC5429525/ /pubmed/28499403 http://dx.doi.org/10.1186/s13567-017-0434-5 Text en © The Author(s) 2017 Open AccessThis 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.
spellingShingle Research Article
Liu, Zehui
Liu, Yangkun
Zhang, Yuanyuan
Yang, Yajuan
Ren, Jingjing
Zhang, Xiaoying
Du, Enqi
Surface displaying of swine IgG1 Fc enhances baculovirus-vectored vaccine efficacy by facilitating viral complement escape and mammalian cell transduction
title Surface displaying of swine IgG1 Fc enhances baculovirus-vectored vaccine efficacy by facilitating viral complement escape and mammalian cell transduction
title_full Surface displaying of swine IgG1 Fc enhances baculovirus-vectored vaccine efficacy by facilitating viral complement escape and mammalian cell transduction
title_fullStr Surface displaying of swine IgG1 Fc enhances baculovirus-vectored vaccine efficacy by facilitating viral complement escape and mammalian cell transduction
title_full_unstemmed Surface displaying of swine IgG1 Fc enhances baculovirus-vectored vaccine efficacy by facilitating viral complement escape and mammalian cell transduction
title_short Surface displaying of swine IgG1 Fc enhances baculovirus-vectored vaccine efficacy by facilitating viral complement escape and mammalian cell transduction
title_sort surface displaying of swine igg1 fc enhances baculovirus-vectored vaccine efficacy by facilitating viral complement escape and mammalian cell transduction
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5429525/
https://www.ncbi.nlm.nih.gov/pubmed/28499403
http://dx.doi.org/10.1186/s13567-017-0434-5
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