Cargando…

Tetravalent recombinant dengue virus-like particles as potential vaccine candidates: immunological properties

BACKGROUND: Currently, a licensed vaccine for Dengue Virus (DENV) is not yet available. Virus-like particles (VLP) have shown considerable promise for use as vaccines and have many advantages compared to many other types of viral vaccines. VLPs have been found to have high immunogenic potencies, pro...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Yan, Zhou, Junmei, Yu, Zhizhun, Fang, Danyun, Fu, Chunyun, Zhu, Xun, He, Zhenjian, Yan, Huijun, Jiang, Lifang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4396058/
https://www.ncbi.nlm.nih.gov/pubmed/25520151
http://dx.doi.org/10.1186/s12866-014-0233-3
_version_ 1782366532516446208
author Liu, Yan
Zhou, Junmei
Yu, Zhizhun
Fang, Danyun
Fu, Chunyun
Zhu, Xun
He, Zhenjian
Yan, Huijun
Jiang, Lifang
author_facet Liu, Yan
Zhou, Junmei
Yu, Zhizhun
Fang, Danyun
Fu, Chunyun
Zhu, Xun
He, Zhenjian
Yan, Huijun
Jiang, Lifang
author_sort Liu, Yan
collection PubMed
description BACKGROUND: Currently, a licensed vaccine for Dengue Virus (DENV) is not yet available. Virus-like particles (VLP) have shown considerable promise for use as vaccines and have many advantages compared to many other types of viral vaccines. VLPs have been found to have high immunogenic potencies, providing protection against various pathogens. RESULTS: In the current study, four DENV-VLP serotypes were successfully expressed in Pichia pastoris, based on co-expression of the prM and E proteins. The effects of a tetravalent VLP vaccine were also examined. Immunization with purified, recombinant, tetravalent DENV1-4 VLPs induced specific antibodies against all DENV1-4 antigens in mice. The antibody titers were higher after immunization with the tetravalent VLP vaccine compared to titers after immunization with any of the dengue serotype VLPs alone. Indirect immunofluorescence assay (IFA) results indicated that sera from VLP immunized mice recognized the native viral antigens. TNF-α and IL-10 were significantly higher in mice immunized with tetravalent DENV-VLP compared to those mice received PBS. The tetravalent VLP appeared to stimulate neutralizing antibodies against each viral serotype, as shown by PRNT(50) analysis (1:32 against DENV1 and 2, and 1:16 against DENV3 and 4). The highest titers with the tetravalent VLP vaccine were still a little lower than the monovalent VLP against the corresponding serotype. The protection rates of tetravalent DENV-VLP immune sera against challenges with DENV1 to 4 serotypes in suckling mice were 77, 92, 100, and 100%, respectively, indicating greater protective efficacy compared with monovalent immune sera. CONCLUSIONS: Our results provide an important basis for the development of the dengue VLP as a promising non-infectious candidate vaccine for dengue infection.
format Online
Article
Text
id pubmed-4396058
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-43960582015-04-14 Tetravalent recombinant dengue virus-like particles as potential vaccine candidates: immunological properties Liu, Yan Zhou, Junmei Yu, Zhizhun Fang, Danyun Fu, Chunyun Zhu, Xun He, Zhenjian Yan, Huijun Jiang, Lifang BMC Microbiol Research Article BACKGROUND: Currently, a licensed vaccine for Dengue Virus (DENV) is not yet available. Virus-like particles (VLP) have shown considerable promise for use as vaccines and have many advantages compared to many other types of viral vaccines. VLPs have been found to have high immunogenic potencies, providing protection against various pathogens. RESULTS: In the current study, four DENV-VLP serotypes were successfully expressed in Pichia pastoris, based on co-expression of the prM and E proteins. The effects of a tetravalent VLP vaccine were also examined. Immunization with purified, recombinant, tetravalent DENV1-4 VLPs induced specific antibodies against all DENV1-4 antigens in mice. The antibody titers were higher after immunization with the tetravalent VLP vaccine compared to titers after immunization with any of the dengue serotype VLPs alone. Indirect immunofluorescence assay (IFA) results indicated that sera from VLP immunized mice recognized the native viral antigens. TNF-α and IL-10 were significantly higher in mice immunized with tetravalent DENV-VLP compared to those mice received PBS. The tetravalent VLP appeared to stimulate neutralizing antibodies against each viral serotype, as shown by PRNT(50) analysis (1:32 against DENV1 and 2, and 1:16 against DENV3 and 4). The highest titers with the tetravalent VLP vaccine were still a little lower than the monovalent VLP against the corresponding serotype. The protection rates of tetravalent DENV-VLP immune sera against challenges with DENV1 to 4 serotypes in suckling mice were 77, 92, 100, and 100%, respectively, indicating greater protective efficacy compared with monovalent immune sera. CONCLUSIONS: Our results provide an important basis for the development of the dengue VLP as a promising non-infectious candidate vaccine for dengue infection. BioMed Central 2014-12-18 /pmc/articles/PMC4396058/ /pubmed/25520151 http://dx.doi.org/10.1186/s12866-014-0233-3 Text en © Liu et al.; licensee BioMed Central. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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, Yan
Zhou, Junmei
Yu, Zhizhun
Fang, Danyun
Fu, Chunyun
Zhu, Xun
He, Zhenjian
Yan, Huijun
Jiang, Lifang
Tetravalent recombinant dengue virus-like particles as potential vaccine candidates: immunological properties
title Tetravalent recombinant dengue virus-like particles as potential vaccine candidates: immunological properties
title_full Tetravalent recombinant dengue virus-like particles as potential vaccine candidates: immunological properties
title_fullStr Tetravalent recombinant dengue virus-like particles as potential vaccine candidates: immunological properties
title_full_unstemmed Tetravalent recombinant dengue virus-like particles as potential vaccine candidates: immunological properties
title_short Tetravalent recombinant dengue virus-like particles as potential vaccine candidates: immunological properties
title_sort tetravalent recombinant dengue virus-like particles as potential vaccine candidates: immunological properties
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4396058/
https://www.ncbi.nlm.nih.gov/pubmed/25520151
http://dx.doi.org/10.1186/s12866-014-0233-3
work_keys_str_mv AT liuyan tetravalentrecombinantdengueviruslikeparticlesaspotentialvaccinecandidatesimmunologicalproperties
AT zhoujunmei tetravalentrecombinantdengueviruslikeparticlesaspotentialvaccinecandidatesimmunologicalproperties
AT yuzhizhun tetravalentrecombinantdengueviruslikeparticlesaspotentialvaccinecandidatesimmunologicalproperties
AT fangdanyun tetravalentrecombinantdengueviruslikeparticlesaspotentialvaccinecandidatesimmunologicalproperties
AT fuchunyun tetravalentrecombinantdengueviruslikeparticlesaspotentialvaccinecandidatesimmunologicalproperties
AT zhuxun tetravalentrecombinantdengueviruslikeparticlesaspotentialvaccinecandidatesimmunologicalproperties
AT hezhenjian tetravalentrecombinantdengueviruslikeparticlesaspotentialvaccinecandidatesimmunologicalproperties
AT yanhuijun tetravalentrecombinantdengueviruslikeparticlesaspotentialvaccinecandidatesimmunologicalproperties
AT jianglifang tetravalentrecombinantdengueviruslikeparticlesaspotentialvaccinecandidatesimmunologicalproperties