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Chimeric epitope vaccine against Leptospira interrogans infection and induced specific immunity in guinea pigs
BACKGROUND: Leptospirosis is an important reemerging zoonosis, with more than half a million cases reported annually, and is caused by pathogenic Leptospira species. Development of a universal vaccine is one of the major strategic goals to overcome the disease burden of leptospirosis. In this study,...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5064800/ https://www.ncbi.nlm.nih.gov/pubmed/27737644 http://dx.doi.org/10.1186/s12866-016-0852-y |
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author | Lin, Xu’ai Xiao, Guohui Luo, Dongjiao Kong, Liangliang Chen, Xu Sun, Dexter Yan, Jie |
author_facet | Lin, Xu’ai Xiao, Guohui Luo, Dongjiao Kong, Liangliang Chen, Xu Sun, Dexter Yan, Jie |
author_sort | Lin, Xu’ai |
collection | PubMed |
description | BACKGROUND: Leptospirosis is an important reemerging zoonosis, with more than half a million cases reported annually, and is caused by pathogenic Leptospira species. Development of a universal vaccine is one of the major strategic goals to overcome the disease burden of leptospirosis. In this study, a chimeric multi-epitope protein-based vaccine was designed and tested for its potency to induce a specific immune response and provide protection against L. interrogans infection. RESULTS: The protein, containing four repeats of six T- and B-cell combined epitopes from the leptospiral outer membrane proteins, OmpL1, LipL32 and LipL21, was expressed and purified. Western blot analysis showed that the recombinant protein (named r4R) mainly expressed in a soluble pattern, and reacted with antibodies raised in rabbit against heat-killed Leptospira and in guinea pigs against the r4R vaccine. Microscopic agglutination tests showed that r4R antisera was immunological cross-reactive with a range of Chinese standard reference strains of Leptospira belonging to different serogroups. In guinea pigs, the r4R vaccine induced a Th1-biased immune response, as reflected by the IgG2a/IgG1 ratio and cytokine production of stimulated splenocytes derived from immunized animals. Finally, r4R-immunized guinea pigs showed increased survival of lethal Leptospira challenges compared with PBS-immunized animals and tissue damage and leptospiral colonization of the kidney were reduced. CONCLUSIONS: The multi-epitope chimeric r4R protein is a promising antigen for the development of a universal cross-reactive vaccine against leptospirosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12866-016-0852-y) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5064800 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-50648002016-10-18 Chimeric epitope vaccine against Leptospira interrogans infection and induced specific immunity in guinea pigs Lin, Xu’ai Xiao, Guohui Luo, Dongjiao Kong, Liangliang Chen, Xu Sun, Dexter Yan, Jie BMC Microbiol Research Article BACKGROUND: Leptospirosis is an important reemerging zoonosis, with more than half a million cases reported annually, and is caused by pathogenic Leptospira species. Development of a universal vaccine is one of the major strategic goals to overcome the disease burden of leptospirosis. In this study, a chimeric multi-epitope protein-based vaccine was designed and tested for its potency to induce a specific immune response and provide protection against L. interrogans infection. RESULTS: The protein, containing four repeats of six T- and B-cell combined epitopes from the leptospiral outer membrane proteins, OmpL1, LipL32 and LipL21, was expressed and purified. Western blot analysis showed that the recombinant protein (named r4R) mainly expressed in a soluble pattern, and reacted with antibodies raised in rabbit against heat-killed Leptospira and in guinea pigs against the r4R vaccine. Microscopic agglutination tests showed that r4R antisera was immunological cross-reactive with a range of Chinese standard reference strains of Leptospira belonging to different serogroups. In guinea pigs, the r4R vaccine induced a Th1-biased immune response, as reflected by the IgG2a/IgG1 ratio and cytokine production of stimulated splenocytes derived from immunized animals. Finally, r4R-immunized guinea pigs showed increased survival of lethal Leptospira challenges compared with PBS-immunized animals and tissue damage and leptospiral colonization of the kidney were reduced. CONCLUSIONS: The multi-epitope chimeric r4R protein is a promising antigen for the development of a universal cross-reactive vaccine against leptospirosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12866-016-0852-y) contains supplementary material, which is available to authorized users. BioMed Central 2016-10-14 /pmc/articles/PMC5064800/ /pubmed/27737644 http://dx.doi.org/10.1186/s12866-016-0852-y Text en © The Author(s). 2016 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 Lin, Xu’ai Xiao, Guohui Luo, Dongjiao Kong, Liangliang Chen, Xu Sun, Dexter Yan, Jie Chimeric epitope vaccine against Leptospira interrogans infection and induced specific immunity in guinea pigs |
title | Chimeric epitope vaccine against Leptospira interrogans infection and induced specific immunity in guinea pigs |
title_full | Chimeric epitope vaccine against Leptospira interrogans infection and induced specific immunity in guinea pigs |
title_fullStr | Chimeric epitope vaccine against Leptospira interrogans infection and induced specific immunity in guinea pigs |
title_full_unstemmed | Chimeric epitope vaccine against Leptospira interrogans infection and induced specific immunity in guinea pigs |
title_short | Chimeric epitope vaccine against Leptospira interrogans infection and induced specific immunity in guinea pigs |
title_sort | chimeric epitope vaccine against leptospira interrogans infection and induced specific immunity in guinea pigs |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5064800/ https://www.ncbi.nlm.nih.gov/pubmed/27737644 http://dx.doi.org/10.1186/s12866-016-0852-y |
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