减毒的 PruΔgra72 刚地弓形虫活菌株能诱导小鼠对急性和慢性弓形虫病产生强大的保护性免疫力。

IF 3 2区 医学 Q1 PARASITOLOGY
Jing Li, Yu Kang, Ze-Xuan Wu, Shu-Feng Yang, Yu-Yang Tian, Xing-Quan Zhu, Xiao-Nan Zheng
{"title":"减毒的 PruΔgra72 刚地弓形虫活菌株能诱导小鼠对急性和慢性弓形虫病产生强大的保护性免疫力。","authors":"Jing Li, Yu Kang, Ze-Xuan Wu, Shu-Feng Yang, Yu-Yang Tian, Xing-Quan Zhu, Xiao-Nan Zheng","doi":"10.1186/s13071-024-06461-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Toxoplasma gondii is an intracellular opportunistic pathogenic protozoan that poses serious threats, particularly in immunocompromised individuals. In the absence of a robust prophylactic measure, the mitigation and management of toxoplasmosis present formidable challenges to public health. We recently found that GRA72 plays an important role in parasitophorous vacuole (PV) morphology, growth and virulence of T. gondii. However, whether gra72-deficient strain can be used as a vaccine remains unknown.</p><p><strong>Methods: </strong>We first examined the attenuated virulence of gra72 gene knockout strain (PruΔgra72) and the parasite load in organs of the infected mice. Subsequently, we evaluated the immune-protective effects of the PruΔgra72 vaccination against challenge with various types of T. gondii tachyzoites and Pru cysts. Furthermore, levels of antibodies and cytokines induced by PruΔgra72 vaccination were examined. Statistical analysis was conducted by Student's t-test or Mantel-Cox log-rank test based on data obtained from three independent experiments with GraphPad Prism 8.0.</p><p><strong>Results: </strong>We found that PruΔgra72 strain exhibited a significantly attenuated virulence even at the highest dose of 5 × 10<sup>7</sup> tachyzoites in Kunming mice model. The significant decrease of brain cyst burden and parasite load in the organs of the PruΔgra72-infected mice suggested its potentiality as a live-attenuated vaccine. Hence, we explored the protective immunity of PruΔgra72 vaccination against toxoplasmosis. Results showed that vaccination with 5 × 10<sup>6</sup> PruΔgra72 tachyzoites triggered a strong and sustained Th1-biased immune response, marked by significantly increased levels of anti-T. gondii IgG antibodies, and significantly higher levels of Th1 type cytokines (IL-2, IL-12 and IFN-γ) compared to that of Th2 type (IL-4 and IL-10). Vaccination with 5 × 10<sup>6</sup> PruΔgra72 tachyzoites in mice conferred long-term protection against T. gondii infection by less virulent tachyzoites (ToxoDB#9 PYS and Pru strains) and Pru cysts, provided partial protection against acute infection by high virulent Type I RH tachyzoites and significantly decreased brain cyst burden of chronically infected mice.</p><p><strong>Conclusions: </strong>The avirulent PruΔgra72 induced strong protective immunity against acute and chronic T. gondii infection and is a promising candidate for developing a safe and effective live-attenuated vaccine against T. gondii infection.</p>","PeriodicalId":19793,"journal":{"name":"Parasites & Vectors","volume":null,"pages":null},"PeriodicalIF":3.0000,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378421/pdf/","citationCount":"0","resultStr":"{\"title\":\"Live-attenuated PruΔgra72 strain of Toxoplasma gondii induces strong protective immunity against acute and chronic toxoplasmosis in mice.\",\"authors\":\"Jing Li, Yu Kang, Ze-Xuan Wu, Shu-Feng Yang, Yu-Yang Tian, Xing-Quan Zhu, Xiao-Nan Zheng\",\"doi\":\"10.1186/s13071-024-06461-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Toxoplasma gondii is an intracellular opportunistic pathogenic protozoan that poses serious threats, particularly in immunocompromised individuals. In the absence of a robust prophylactic measure, the mitigation and management of toxoplasmosis present formidable challenges to public health. We recently found that GRA72 plays an important role in parasitophorous vacuole (PV) morphology, growth and virulence of T. gondii. However, whether gra72-deficient strain can be used as a vaccine remains unknown.</p><p><strong>Methods: </strong>We first examined the attenuated virulence of gra72 gene knockout strain (PruΔgra72) and the parasite load in organs of the infected mice. Subsequently, we evaluated the immune-protective effects of the PruΔgra72 vaccination against challenge with various types of T. gondii tachyzoites and Pru cysts. Furthermore, levels of antibodies and cytokines induced by PruΔgra72 vaccination were examined. Statistical analysis was conducted by Student's t-test or Mantel-Cox log-rank test based on data obtained from three independent experiments with GraphPad Prism 8.0.</p><p><strong>Results: </strong>We found that PruΔgra72 strain exhibited a significantly attenuated virulence even at the highest dose of 5 × 10<sup>7</sup> tachyzoites in Kunming mice model. The significant decrease of brain cyst burden and parasite load in the organs of the PruΔgra72-infected mice suggested its potentiality as a live-attenuated vaccine. Hence, we explored the protective immunity of PruΔgra72 vaccination against toxoplasmosis. Results showed that vaccination with 5 × 10<sup>6</sup> PruΔgra72 tachyzoites triggered a strong and sustained Th1-biased immune response, marked by significantly increased levels of anti-T. gondii IgG antibodies, and significantly higher levels of Th1 type cytokines (IL-2, IL-12 and IFN-γ) compared to that of Th2 type (IL-4 and IL-10). Vaccination with 5 × 10<sup>6</sup> PruΔgra72 tachyzoites in mice conferred long-term protection against T. gondii infection by less virulent tachyzoites (ToxoDB#9 PYS and Pru strains) and Pru cysts, provided partial protection against acute infection by high virulent Type I RH tachyzoites and significantly decreased brain cyst burden of chronically infected mice.</p><p><strong>Conclusions: </strong>The avirulent PruΔgra72 induced strong protective immunity against acute and chronic T. gondii infection and is a promising candidate for developing a safe and effective live-attenuated vaccine against T. gondii infection.</p>\",\"PeriodicalId\":19793,\"journal\":{\"name\":\"Parasites & Vectors\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2024-09-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378421/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Parasites & Vectors\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13071-024-06461-9\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PARASITOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Parasites & Vectors","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13071-024-06461-9","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PARASITOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

背景:弓形虫(Toxoplasma gondii)是一种细胞内机会致病原生动物,尤其对免疫力低下的人构成严重威胁。由于缺乏强有力的预防措施,弓形虫病的缓解和管理给公共卫生带来了严峻的挑战。我们最近发现,GRA72 在弓形虫的寄生泡(PV)形态、生长和毒力方面发挥着重要作用。然而,GRA72缺陷株能否用作疫苗仍是未知数:方法:我们首先检测了gra72基因敲除株(PruΔgra72)的减毒性和感染小鼠器官中的寄生虫量。随后,我们评估了接种 PruΔgra72 疫苗对各种类型的淋病双鞭毛虫和 Pru 包囊的免疫保护作用。此外,还检测了接种 PruΔgra72 疫苗后诱导的抗体和细胞因子水平。使用 GraphPad Prism 8.0 对三个独立实验的数据进行统计分析,采用学生 t 检验或 Mantel-Cox 对数秩检验:我们发现,在昆明小鼠模型中,PruΔgra72株即使在最高剂量5×107孑孓时也表现出明显的毒力减弱。PruΔgra72感染小鼠脑囊肿负荷和寄生虫在器官中的负荷明显减少,这表明它具有作为减毒活疫苗的潜力。因此,我们探讨了接种 PruΔgra72 疫苗对弓形虫病的保护性免疫。结果表明,接种 5 × 106 PruΔgra72 支原体疫苗会引发强烈而持续的 Th1 型免疫反应,抗弓形虫 IgG 抗体水平显著提高,Th1 型细胞因子(IL-2、IL-12 和 IFN-γ)水平显著高于 Th2 型细胞因子(IL-4 和 IL-10)。给小鼠接种5×106 PruΔgra72速虫疫苗可长期保护其免受毒性较低的速虫(ToxoDB#9 PYS和Pru株)和Pru囊虫的感染,部分保护其免受毒性较高的I型RH速虫的急性感染,并显著减少慢性感染小鼠的脑囊肿负荷:结论:无病毒的PruΔgra72对急性和慢性淋病感染具有很强的保护性免疫力,是开发安全有效的淋病减毒活疫苗的理想候选菌株。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Live-attenuated PruΔgra72 strain of Toxoplasma gondii induces strong protective immunity against acute and chronic toxoplasmosis in mice.

Background: Toxoplasma gondii is an intracellular opportunistic pathogenic protozoan that poses serious threats, particularly in immunocompromised individuals. In the absence of a robust prophylactic measure, the mitigation and management of toxoplasmosis present formidable challenges to public health. We recently found that GRA72 plays an important role in parasitophorous vacuole (PV) morphology, growth and virulence of T. gondii. However, whether gra72-deficient strain can be used as a vaccine remains unknown.

Methods: We first examined the attenuated virulence of gra72 gene knockout strain (PruΔgra72) and the parasite load in organs of the infected mice. Subsequently, we evaluated the immune-protective effects of the PruΔgra72 vaccination against challenge with various types of T. gondii tachyzoites and Pru cysts. Furthermore, levels of antibodies and cytokines induced by PruΔgra72 vaccination were examined. Statistical analysis was conducted by Student's t-test or Mantel-Cox log-rank test based on data obtained from three independent experiments with GraphPad Prism 8.0.

Results: We found that PruΔgra72 strain exhibited a significantly attenuated virulence even at the highest dose of 5 × 107 tachyzoites in Kunming mice model. The significant decrease of brain cyst burden and parasite load in the organs of the PruΔgra72-infected mice suggested its potentiality as a live-attenuated vaccine. Hence, we explored the protective immunity of PruΔgra72 vaccination against toxoplasmosis. Results showed that vaccination with 5 × 106 PruΔgra72 tachyzoites triggered a strong and sustained Th1-biased immune response, marked by significantly increased levels of anti-T. gondii IgG antibodies, and significantly higher levels of Th1 type cytokines (IL-2, IL-12 and IFN-γ) compared to that of Th2 type (IL-4 and IL-10). Vaccination with 5 × 106 PruΔgra72 tachyzoites in mice conferred long-term protection against T. gondii infection by less virulent tachyzoites (ToxoDB#9 PYS and Pru strains) and Pru cysts, provided partial protection against acute infection by high virulent Type I RH tachyzoites and significantly decreased brain cyst burden of chronically infected mice.

Conclusions: The avirulent PruΔgra72 induced strong protective immunity against acute and chronic T. gondii infection and is a promising candidate for developing a safe and effective live-attenuated vaccine against T. gondii infection.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Parasites & Vectors
Parasites & Vectors 医学-寄生虫学
CiteScore
6.30
自引率
9.40%
发文量
433
审稿时长
1.4 months
期刊介绍: Parasites & Vectors is an open access, peer-reviewed online journal dealing with the biology of parasites, parasitic diseases, intermediate hosts, vectors and vector-borne pathogens. Manuscripts published in this journal will be available to all worldwide, with no barriers to access, immediately following acceptance. However, authors retain the copyright of their material and may use it, or distribute it, as they wish. Manuscripts on all aspects of the basic and applied biology of parasites, intermediate hosts, vectors and vector-borne pathogens will be considered. In addition to the traditional and well-established areas of science in these fields, we also aim to provide a vehicle for publication of the rapidly developing resources and technology in parasite, intermediate host and vector genomics and their impacts on biological research. We are able to publish large datasets and extensive results, frequently associated with genomic and post-genomic technologies, which are not readily accommodated in traditional journals. Manuscripts addressing broader issues, for example economics, social sciences and global climate change in relation to parasites, vectors and disease control, are also welcomed.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信