• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

在一种用于治疗期间免疫治疗的严格小鼠模型中，腺病毒结核病疫苗具有免疫原性但无疗效。

Immunogenicity without Efficacy of an Adenoviral Tuberculosis Vaccine in a Stringent Mouse Model for Immunotherapy during Treatment.

作者信息

Alyahya S Anisah, Nolan Scott T, Smith Cara M R, Bishai William R, Sadoff Jerald, Lamichhane Gyanu

机构信息

Crucell Holland B.V., Janssen Infectious Diseases and Vaccines, Leiden, The Netherlands.

Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.

出版信息

PLoS One. 2015 May 21;10(5):e0127907. doi: 10.1371/journal.pone.0127907. eCollection 2015.

DOI:10.1371/journal.pone.0127907
PMID:25996375
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4440646/
Abstract

To investigate if bacterial persistence during TB drug treatment could be overcome by modulation of host immunity, we adapted a clinically-relevant model developed for the evaluation of new drugs and examined if immunotherapy with two adenoviral vaccines, Ad35-TBS (AERAS-402) and Ad26-TBS, could shorten therapy in mice. Even though immunotherapy resulted in strong splenic IFN-γ responses, no effect on bacterial replication in the lungs was seen. Multiplex assay analysis of lung samples revealed the absence of cytokine augmentation such as IFN-γ, TNF-α and IL-2, suggesting that immunization failed to induce immunity in the lungs. In this model, we show that IFN-γ levels were not associated with protection against disease relapse. The results obtained from our study raise questions regarding the traits of protective TB immunity that are relevant for the development of future immunotherapeutic and post-exposure vaccination strategies.

摘要

为了研究在结核病药物治疗期间细菌的持续存在是否可以通过调节宿主免疫来克服，我们采用了一个为评估新药而开发的临床相关模型，并研究了两种腺病毒疫苗Ad35-TBS（AERAS-402）和Ad26-TBS的免疫疗法是否可以缩短小鼠的治疗时间。尽管免疫疗法导致脾脏产生强烈的IFN-γ反应，但未观察到对肺部细菌复制有任何影响。对肺样本的多重分析显示缺乏细胞因子增强，如IFN-γ、TNF-α和IL-2，这表明免疫未能在肺部诱导免疫。在这个模型中，我们表明IFN-γ水平与预防疾病复发无关。我们的研究结果对与未来免疫治疗和暴露后疫苗接种策略发展相关的保护性结核病免疫特征提出了疑问。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be10/4440646/e8fc5f6d092a/pone.0127907.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be10/4440646/1c65cd0abf60/pone.0127907.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be10/4440646/44d9d1d73cc7/pone.0127907.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be10/4440646/44cdaa981a8b/pone.0127907.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be10/4440646/576ea23ccbd6/pone.0127907.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be10/4440646/491f3167ba5c/pone.0127907.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be10/4440646/9cdde0c2b068/pone.0127907.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be10/4440646/e8fc5f6d092a/pone.0127907.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be10/4440646/1c65cd0abf60/pone.0127907.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be10/4440646/44d9d1d73cc7/pone.0127907.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be10/4440646/44cdaa981a8b/pone.0127907.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be10/4440646/576ea23ccbd6/pone.0127907.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be10/4440646/491f3167ba5c/pone.0127907.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be10/4440646/9cdde0c2b068/pone.0127907.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be10/4440646/e8fc5f6d092a/pone.0127907.g007.jpg

相似文献

1
Immunogenicity without Efficacy of an Adenoviral Tuberculosis Vaccine in a Stringent Mouse Model for Immunotherapy during Treatment.在一种用于治疗期间免疫治疗的严格小鼠模型中，腺病毒结核病疫苗具有免疫原性但无疗效。
PLoS One. 2015 May 21;10(5):e0127907. doi: 10.1371/journal.pone.0127907. eCollection 2015.
2
Protective immune responses to a recombinant adenovirus type 35 tuberculosis vaccine in two mouse strains: CD4 and CD8 T-cell epitope mapping and role of gamma interferon.两种小鼠品系对重组35型腺病毒结核病疫苗的保护性免疫反应：CD4和CD8 T细胞表位图谱分析及γ干扰素的作用
Infect Immun. 2007 Aug;75(8):4105-15. doi: 10.1128/IAI.00004-07. Epub 2007 May 25.
3
Immunogenicity and therapeutic effects of Ag85A/B chimeric DNA vaccine in mice infected with Mycobacterium tuberculosis.Ag85A/B嵌合DNA疫苗对感染结核分枝杆菌小鼠的免疫原性及治疗效果
FEMS Immunol Med Microbiol. 2012 Dec;66(3):419-26. doi: 10.1111/1574-695X.12008.
4
A multistage-polyepitope vaccine protects against Mycobacterium tuberculosis infection in HLA-DR3 transgenic mice.一种多阶段多表位疫苗可预防 HLA-DR3 转基因小鼠感染结核分枝杆菌。
Vaccine. 2012 Dec 14;30(52):7513-21. doi: 10.1016/j.vaccine.2012.10.045. Epub 2012 Oct 24.
5
Vaccination with a Sindbis virus-based DNA vaccine expressing antigen 85B induces protective immunity against Mycobacterium tuberculosis.用表达85B抗原的基于辛德毕斯病毒的DNA疫苗进行接种可诱导针对结核分枝杆菌的保护性免疫。
Infect Immun. 2005 Nov;73(11):7727-35. doi: 10.1128/IAI.73.11.7727-7735.2005.
6
[Novel vaccines against M. tuberculosis].[新型抗结核分枝杆菌疫苗]
Kekkaku. 2006 Dec;81(12):745-51.
7
Immunogenicity and protective efficacy of novel Mycobacterium tuberculosis antigens.新型结核分枝杆菌抗原的免疫原性和保护效力。
Vaccine. 2013 Sep 23;31(41):4641-6. doi: 10.1016/j.vaccine.2013.07.032. Epub 2013 Jul 30.
8
Immune responses and protective efficacy of the gene vaccine expressing Ag85B and ESAT6 fusion protein from Mycobacterium tuberculosis.表达结核分枝杆菌Ag85B和ESAT6融合蛋白的基因疫苗的免疫反应及保护效果
DNA Cell Biol. 2008 Apr;27(4):199-207. doi: 10.1089/dna.2007.0648.
9
[Immunoprophylaxis of recombinant Mycobacterium vaccae secreted MPT64 of Mycobacterium tuberculosis].[重组母牛分枝杆菌分泌结核分枝杆菌MPT64的免疫预防]
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2009 Mar;25(3):211-4.
10
Immunogenicity and protective efficacy of a DNA vaccine encoding the fusion protein of mycobacterium heat shock protein 65 (Hsp65) with human interleukin-2 against Mycobacterium tuberculosis in BALB/c mice.编码结核分枝杆菌热休克蛋白65（Hsp65）与人白细胞介素-2融合蛋白的DNA疫苗对BALB/c小鼠结核分枝杆菌的免疫原性和保护效力
APMIS. 2008 Dec;116(12):1071-81. doi: 10.1111/j.1600-0463.2008.01095.x.

引用本文的文献

1
Mucosal and systemic immune responses after a single intranasal dose of nanoparticle and spore-based subunit vaccines in mice with pre-existing lung mycobacterial immunity.经鼻腔给予纳米颗粒和孢子亚单位疫苗后，对预先存在肺部分枝杆菌免疫的小鼠的粘膜和全身免疫反应。
Front Immunol. 2023 Dec 7;14:1306449. doi: 10.3389/fimmu.2023.1306449. eCollection 2023.
2
An Immunoinformatics-Based Study of Mycobacterium tuberculosis Region of Difference-2 Uncharacterized Protein (Rv1987) as a Potential Subunit Vaccine Candidate for Preliminary Ex Vivo Analysis.基于免疫信息学的结核分枝杆菌差异区 2 未鉴定蛋白（Rv1987）作为潜在亚单位疫苗候选物的初步体外分析。
Appl Biochem Biotechnol. 2024 Apr;196(4):2367-2395. doi: 10.1007/s12010-023-04658-9. Epub 2023 Jul 27.
3

本文引用的文献

1
The novel tuberculosis vaccine, AERAS-402, is safe in healthy infants previously vaccinated with BCG, and induces dose-dependent CD4 and CD8T cell responses.新型结核病疫苗AERAS-402在先前接种过卡介苗的健康婴儿中是安全的，并能诱导剂量依赖性的CD4和CD8 T细胞反应。
Vaccine. 2014 Oct 14;32(45):5908-17. doi: 10.1016/j.vaccine.2014.09.001. Epub 2014 Sep 10.
2
Aerosol vaccination with AERAS-402 elicits robust cellular immune responses in the lungs of rhesus macaques but fails to protect against high-dose Mycobacterium tuberculosis challenge.气溶胶免疫接种 AERAS-402 可在恒河猴肺部引发强烈的细胞免疫应答，但不能预防高剂量结核分枝杆菌挑战。
J Immunol. 2014 Aug 15;193(4):1799-811. doi: 10.4049/jimmunol.1400676. Epub 2014 Jul 14.
3
Therapeutic Effect of Subunit Vaccine AEC/BC02 on Post-Chemotherapy Relapse Using a Latent Infection Murine Model.亚单位疫苗AEC/BC02对化疗后复发的潜伏感染小鼠模型的治疗效果
Vaccines (Basel). 2022 May 23;10(5):825. doi: 10.3390/vaccines10050825.
4
Vaccines based on replication incompetent Ad26 viral vectors: Standardized template with key considerations for a risk/benefit assessment.基于复制缺陷型 Ad26 病毒载体的疫苗：标准化模板及风险/获益评估的关键考虑因素。
Vaccine. 2021 May 21;39(22):3081-3101. doi: 10.1016/j.vaccine.2020.09.018. Epub 2020 Oct 3.
5
Advancing Immunotherapeutic Vaccine Strategies Against Pulmonary Tuberculosis.推进抗肺结核免疫治疗疫苗策略
Front Immunol. 2020 Sep 9;11:557809. doi: 10.3389/fimmu.2020.557809. eCollection 2020.
6
Single-Dose Mucosal Immunotherapy With Chimpanzee Adenovirus-Based Vaccine Accelerates Tuberculosis Disease Control and Limits Its Rebound After Antibiotic Cessation.单次黏膜免疫接种基于 chimpanzee 腺病毒的疫苗可加速结核病的控制，并限制抗生素停药后的反弹。
J Infect Dis. 2019 Sep 13;220(8):1355-1366. doi: 10.1093/infdis/jiz306.
7
A Partial E3 Deletion in Replication-Defective Adenoviral Vectors Allows for Stable Expression of Potentially Toxic Transgene Products.复制缺陷型腺病毒载体中的部分E3缺失允许潜在毒性转基因产物的稳定表达。
Hum Gene Ther Methods. 2016 Oct;27(5):187-196. doi: 10.1089/hgtb.2016.044. Epub 2016 Sep 7.
Therapeutic vaccines for tuberculosis--a systematic review.
用于结核病的治疗性疫苗——一项系统综述
Vaccine. 2014 May 30;32(26):3162-8. doi: 10.1016/j.vaccine.2014.03.047. Epub 2014 Apr 13.
4
High-frequency vaccine-induced CD8⁺ T cells specific for an epitope naturally processed during infection with Mycobacterium tuberculosis do not confer protection.高频疫苗诱导的针对结核分枝杆菌感染期间自然加工的表位的 CD8+T 细胞并不能提供保护。
Eur J Immunol. 2014 Jun;44(6):1699-709. doi: 10.1002/eji.201344358. Epub 2014 Mar 27.
5
In search of a new paradigm for protective immunity to TB.寻找针对结核病的保护性免疫新范式。
Nat Rev Microbiol. 2014 Apr;12(4):289-99. doi: 10.1038/nrmicro3230. Epub 2014 Mar 3.
6
iNKT cell production of GM-CSF controls Mycobacterium tuberculosis.自然杀伤T细胞产生的粒细胞-巨噬细胞集落刺激因子可控制结核分枝杆菌。
PLoS Pathog. 2014 Jan;10(1):e1003805. doi: 10.1371/journal.ppat.1003805. Epub 2014 Jan 2.
7
A new unifying theory of the pathogenesis of tuberculosis.一种新的结核病发病机制的统一理论。
Tuberculosis (Edinb). 2014 Jan;94(1):8-14. doi: 10.1016/j.tube.2013.07.004. Epub 2013 Aug 4.
8
Control of chronic mycobacterium tuberculosis infection by CD4 KLRG1- IL-2-secreting central memory cells.通过分泌 IL-2 的 CD4 KLRG1-中央记忆细胞控制慢性结核分枝杆菌感染。
J Immunol. 2013 Jun 15;190(12):6311-9. doi: 10.4049/jimmunol.1300248. Epub 2013 May 15.
9
Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomised, placebo-controlled phase 2b trial.新型结核疫苗 MVA85A 在既往接种过卡介苗婴儿中的安全性和有效性：一项随机、安慰剂对照的 2b 期试验。
Lancet. 2013 Mar 23;381(9871):1021-8. doi: 10.1016/S0140-6736(13)60177-4.
10
What is the cost of diagnosis and management of drug resistant tuberculosis in South Africa?南非耐药结核病的诊断和管理费用是多少？
PLoS One. 2013;8(1):e54587. doi: 10.1371/journal.pone.0054587. Epub 2013 Jan 18.