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Protection via a ROM4 DNA vaccine and peptide against Toxoplasma gondii in BALB/c mice

BACKGROUND: Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite with a broad host range including most warm-blooded animals, including humans. T. gondii surface antigen 1 (SAG1) is a well-characterized T. gondii antigen. T. gondii expresses five nonmitochondrial rhomboid in...

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Autores principales: Han, Yali, Zhou, Aihua, Lu, Gang, Zhao, Guanghui, Wang, Lin, Guo, Jingjing, Song, Pengxia, Zhou, Jian, Zhou, Huaiyu, Cong, Hua, He, Shenyi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5225637/
https://www.ncbi.nlm.nih.gov/pubmed/28077075
http://dx.doi.org/10.1186/s12879-016-2104-z
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author Han, Yali
Zhou, Aihua
Lu, Gang
Zhao, Guanghui
Wang, Lin
Guo, Jingjing
Song, Pengxia
Zhou, Jian
Zhou, Huaiyu
Cong, Hua
He, Shenyi
author_facet Han, Yali
Zhou, Aihua
Lu, Gang
Zhao, Guanghui
Wang, Lin
Guo, Jingjing
Song, Pengxia
Zhou, Jian
Zhou, Huaiyu
Cong, Hua
He, Shenyi
author_sort Han, Yali
collection PubMed
description BACKGROUND: Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite with a broad host range including most warm-blooded animals, including humans. T. gondii surface antigen 1 (SAG1) is a well-characterized T. gondii antigen. T. gondii expresses five nonmitochondrial rhomboid intramembrane proteases, TgROM1-5. TgROM4 is uniformly distributed on the surface of T. gondii and involved in regulating MIC2, MIC3, MIC6, and AMA1 during T. gondii invasion of host cells. Bioinformatics have predicted ROM4 B-cell and T-cell epitopes. Immunization strategy is also a key factor in determining the effectiveness of the immune response and has gained increasing attention in T. gondii vaccine research. In this study, we used a DNA prime-peptide boost vaccination regimen to assess the protective efficacy of various vaccination strategies using TgROM4. METHODS: We identified a polypeptide (YALLGALIPYCVEYWKSIPR) using a bioinformatics approach, and immunized mice using a DNA-prime and polypeptide-boost regimen. BALB/c mice were randomly divided into six groups, including three experimental groups (peptide, pROM4 and pROM4/peptide) and three control groups (PBS, pEGFP-C1 and pSAG1). Mice were then immunized intramuscularly four times. After immunization, IgG and cytokine productions were determined using enzyme-linked immunosorbent assays. The survival time of mice was evaluated after challenge with tachyzoites of T. gondii RH strain. Additionally, the number of cysts in the brain was determined after intragastric challenge with cysts of T. gondii PRU strain. RESULTS: Mice vaccinated with different immunization regimens (peptide, pROM4 and pROM4/peptide) elicited specific humoral and cellular responses, with high levels of IgG, IgG2a, and interferon (IFN)-γ. Moreover, IgG, IgG2a and IFN-γ levels were highest in the pROM4/peptide group. Immunized mice, especially those in the pROM4/peptide group, had prolonged survival times after challenge with tachyzoites and reduced numbers of brain cysts after infection compared with negative controls. CONCLUSION: A DNA prime-peptide boost regimen based on ROM4 elicited the highest level of humoral and cellular immune responses among immunization regimens, and may be a promising approach to increase the efficacy of DNA immunization.
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spelling pubmed-52256372017-01-17 Protection via a ROM4 DNA vaccine and peptide against Toxoplasma gondii in BALB/c mice Han, Yali Zhou, Aihua Lu, Gang Zhao, Guanghui Wang, Lin Guo, Jingjing Song, Pengxia Zhou, Jian Zhou, Huaiyu Cong, Hua He, Shenyi BMC Infect Dis Research Article BACKGROUND: Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite with a broad host range including most warm-blooded animals, including humans. T. gondii surface antigen 1 (SAG1) is a well-characterized T. gondii antigen. T. gondii expresses five nonmitochondrial rhomboid intramembrane proteases, TgROM1-5. TgROM4 is uniformly distributed on the surface of T. gondii and involved in regulating MIC2, MIC3, MIC6, and AMA1 during T. gondii invasion of host cells. Bioinformatics have predicted ROM4 B-cell and T-cell epitopes. Immunization strategy is also a key factor in determining the effectiveness of the immune response and has gained increasing attention in T. gondii vaccine research. In this study, we used a DNA prime-peptide boost vaccination regimen to assess the protective efficacy of various vaccination strategies using TgROM4. METHODS: We identified a polypeptide (YALLGALIPYCVEYWKSIPR) using a bioinformatics approach, and immunized mice using a DNA-prime and polypeptide-boost regimen. BALB/c mice were randomly divided into six groups, including three experimental groups (peptide, pROM4 and pROM4/peptide) and three control groups (PBS, pEGFP-C1 and pSAG1). Mice were then immunized intramuscularly four times. After immunization, IgG and cytokine productions were determined using enzyme-linked immunosorbent assays. The survival time of mice was evaluated after challenge with tachyzoites of T. gondii RH strain. Additionally, the number of cysts in the brain was determined after intragastric challenge with cysts of T. gondii PRU strain. RESULTS: Mice vaccinated with different immunization regimens (peptide, pROM4 and pROM4/peptide) elicited specific humoral and cellular responses, with high levels of IgG, IgG2a, and interferon (IFN)-γ. Moreover, IgG, IgG2a and IFN-γ levels were highest in the pROM4/peptide group. Immunized mice, especially those in the pROM4/peptide group, had prolonged survival times after challenge with tachyzoites and reduced numbers of brain cysts after infection compared with negative controls. CONCLUSION: A DNA prime-peptide boost regimen based on ROM4 elicited the highest level of humoral and cellular immune responses among immunization regimens, and may be a promising approach to increase the efficacy of DNA immunization. BioMed Central 2017-01-11 /pmc/articles/PMC5225637/ /pubmed/28077075 http://dx.doi.org/10.1186/s12879-016-2104-z 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
Han, Yali
Zhou, Aihua
Lu, Gang
Zhao, Guanghui
Wang, Lin
Guo, Jingjing
Song, Pengxia
Zhou, Jian
Zhou, Huaiyu
Cong, Hua
He, Shenyi
Protection via a ROM4 DNA vaccine and peptide against Toxoplasma gondii in BALB/c mice
title Protection via a ROM4 DNA vaccine and peptide against Toxoplasma gondii in BALB/c mice
title_full Protection via a ROM4 DNA vaccine and peptide against Toxoplasma gondii in BALB/c mice
title_fullStr Protection via a ROM4 DNA vaccine and peptide against Toxoplasma gondii in BALB/c mice
title_full_unstemmed Protection via a ROM4 DNA vaccine and peptide against Toxoplasma gondii in BALB/c mice
title_short Protection via a ROM4 DNA vaccine and peptide against Toxoplasma gondii in BALB/c mice
title_sort protection via a rom4 dna vaccine and peptide against toxoplasma gondii in balb/c mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5225637/
https://www.ncbi.nlm.nih.gov/pubmed/28077075
http://dx.doi.org/10.1186/s12879-016-2104-z
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