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本文引用的文献

1
Induction of an Immune-Protective T-Cell Repertoire With Diverse Genetic Coverage by a Novel Viral-Vectored Tuberculosis Vaccine in Humans.新型病毒载体结核病疫苗在人体内诱导具有多种基因覆盖的免疫保护性T细胞库
J Infect Dis. 2016 Dec 15;214(12):1996-2005. doi: 10.1093/infdis/jiw467. Epub 2016 Oct 4.
2
Reconstitution of immune cell in liver and lymph node of adult- and newborn-engrafted humanized mice.成年和新生移植人源化小鼠肝脏和淋巴结中免疫细胞的重建。
BMC Immunol. 2016 Jun 16;17(1):18. doi: 10.1186/s12865-016-0157-9.
3
Pulmonary Tuberculosis in Humanized Mice Infected with HIV-1.感染HIV-1的人源化小鼠中的肺结核
Sci Rep. 2016 Feb 24;6:21522. doi: 10.1038/srep21522.
4
A review of clinical models for the evaluation of human TB vaccines.用于评估人类结核病疫苗的临床模型综述。
Hum Vaccin Immunother. 2016 May 3;12(5):1177-87. doi: 10.1080/21645515.2015.1134407. Epub 2016 Jan 25.
5
Protection Induced by Simultaneous Subcutaneous and Endobronchial Vaccination with BCG/BCG and BCG/Adenovirus Expressing Antigen 85A against Mycobacterium bovis in Cattle.卡介苗/卡介苗和表达抗原85A的卡介苗/腺病毒同时皮下和支气管内接种对牛结核分枝杆菌的免疫保护作用。
PLoS One. 2015 Nov 6;10(11):e0142270. doi: 10.1371/journal.pone.0142270. eCollection 2015.
6
Mucosal vaccination with attenuated Mycobacterium tuberculosis induces strong central memory responses and protects against tuberculosis.用减毒结核分枝杆菌进行黏膜疫苗接种可诱导强烈的中枢记忆反应并预防结核病。
Nat Commun. 2015 Oct 13;6:8533. doi: 10.1038/ncomms9533.
7
AdHu5Ag85A Respiratory Mucosal Boost Immunization Enhances Protection against Pulmonary Tuberculosis in BCG-Primed Non-Human Primates.AdHu5Ag85A呼吸道黏膜加强免疫增强卡介苗初免非人灵长类动物对肺结核的保护作用。
PLoS One. 2015 Aug 7;10(8):e0135009. doi: 10.1371/journal.pone.0135009. eCollection 2015.
8
Animal models in tuberculosis research - where is the beef?结核病研究中的动物模型——实质内容何在？
Expert Opin Drug Discov. 2015;10(8):871-83. doi: 10.1517/17460441.2015.1049529. Epub 2015 Jun 13.
9
Latent Mycobacterium tuberculosis infection.潜伏性结核分枝杆菌感染
N Engl J Med. 2015 May 28;372(22):2127-35. doi: 10.1056/NEJMra1405427.
10
Safety, immunogenicity, and efficacy of the candidate tuberculosis vaccine MVA85A in healthy adults infected with HIV-1: a randomised, placebo-controlled, phase 2 trial.MVA85A 候选结核病疫苗在感染 HIV-1 的健康成年人中的安全性、免疫原性和疗效：一项随机、安慰剂对照、2 期试验。
Lancet Respir Med. 2015 Mar;3(3):190-200. doi: 10.1016/S2213-2600(15)00037-5. Epub 2015 Feb 26.

一种新型病毒载体呼吸道粘膜疫苗在人源化模型系统中增强抗结核免疫力

Enhancement of Antituberculosis Immunity in a Humanized Model System by a Novel Virus-Vectored Respiratory Mucosal Vaccine.

作者信息

Yao Yushi, Lai Rocky, Afkhami Sam, Haddadi Siamak, Zganiacz Anna, Vahedi Fatemeh, Ashkar Ali A, Kaushic Charu, Jeyanathan Mangalakumari, Xing Zhou

机构信息

McMaster Immunology Research Centre.

Department of Pathology & Molecular Medicine.

出版信息

J Infect Dis. 2017 Jul 1;216(1):135-145. doi: 10.1093/infdis/jix252.

DOI:10.1093/infdis/jix252
PMID:28531291
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5853534/
Abstract

BACKGROUND

The translation of preclinically promising novel tuberculosis vaccines to ultimate human applications has been challenged by the lack of animal models with an immune system equivalent to the human immune system in its genetic diversity and level of susceptibility to tuberculosis.

METHODS

We have developed a humanized mice (Hu-mice) tuberculosis model system to investigate the clinical relevance of a novel virus-vectored (VV) tuberculosis vaccine administered via respiratory mucosal or parenteral route.

RESULTS

We find that VV vaccine activates T cells in Hu-mice as it does in human vaccinees. The respiratory mucosal route for delivery of VV vaccine in Hu-mice, but not the parenteral route, significantly reduces the humanlike lung tuberculosis outcomes in a human T-cell-dependent manner.

CONCLUSIONS

Our results suggest that the Hu-mouse can be used to predict the protective efficacy of novel tuberculosis vaccines/strategies before they proceed to large, expensive human trials. This new vaccine testing system will facilitate the global pace of clinical tuberculosis vaccine development.

摘要

背景

临床前有前景的新型结核病疫苗向最终人体应用的转化受到挑战，因为缺乏在遗传多样性和对结核病易感性水平方面与人类免疫系统相当的动物模型。

方法

我们开发了一种人源化小鼠（Hu-小鼠）结核病模型系统，以研究通过呼吸道黏膜或肠胃外途径接种的新型病毒载体（VV）结核病疫苗的临床相关性。

结果

我们发现，VV疫苗在Hu-小鼠中激活T细胞的方式与在人类疫苗接种者中相同。在Hu-小鼠中，通过呼吸道黏膜途径而非肠胃外途径接种VV疫苗，以人类T细胞依赖的方式显著降低了类似人类肺结核的结果。

结论

我们的结果表明，在进行大规模、昂贵的人体试验之前，Hu-小鼠可用于预测新型结核病疫苗/策略的保护效果。这种新的疫苗测试系统将加快全球临床结核病疫苗的开发步伐。