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首页> 外文期刊>Vaccine >The in vivo expressed Mycobacterium tuberculosis (IVE-TB) antigen Rv2034 induces CD4 + T-cells that protect against pulmonary infection in HLA-DR transgenic mice and guinea pigs.
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The in vivo expressed Mycobacterium tuberculosis (IVE-TB) antigen Rv2034 induces CD4 + T-cells that protect against pulmonary infection in HLA-DR transgenic mice and guinea pigs.

机译：体内表达的结核分枝杆菌（IVE-TB）抗原Rv2034诱导了CD4 + T细胞，可保护其免受HLA-DR转基因小鼠和豚鼠的肺部感染。

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Tuberculosis (TB) remains a life-threatening infectious disease of global proportions with serious negative health and economic consequences. The lack of sufficient protection induced by Mycobacterium bovis BCG, the current vaccine for TB, as well as the impact of HIV co-infection and the emergence of drug resistant Mycobacterium tuberculosis ( Mtb) strains all urge for improved vaccines against TB. A minimal requirement for Mtb vaccine antigens is their in vivo expression during Mtb infection and ability to trigger significant immune responses. Recently we identified a new class of Mtb antigens, designated IVE-TB ( in vivo expressed) antigens. These included Rv2034, a protein that was expressed during pulmonary infection and strongly recognized by human T-cells. Here, the in vivo immunogenicity and protective efficacy of Rv2034 was further analyzed using HLA-DR transgenic mice that lack endogenous murine MHC class II molecules. The Rv2034 protein indeed was highly immunogenic in HLA-DR3 transgenic mice and induced HLA-DR3 restricted IFN-gamma +/TNF + and IFN-gamma + CD4 + T-cells, specific for an epitope encoded in peptide 31-50. CD4 + T-cell responses were optimally induced when using TLR9- and TLR3-ligand-adjuvants or CAF09. Rv2034-specific antibodies were observed following immunization with either TLR2-, TLR3-, TLR4-, TLR5-, TLR7- or TLR9-ligands or CAF09. Importantly, immunization with Rv2034 or the hybrid-protein Ag85B-ESAT6-Rv2034 adjuvanted with CpG or CAF09, induced over one log reduction, relative to unvaccinated controls, in the number of bacilli in the lungs of Mtb challenged HLA-DR3 transgenic mice and guinea pigs. These data demonstrate the potential of Rv2034 as a novel, IVE-TB antigen for future TB vaccination.
机译：结核病（TB）仍然是威胁全球的致命性传染病，严重危害健康和经济。牛分枝杆菌卡介苗（目前的结核病疫苗）缺乏足够的保护作用，以及HIV合并感染的影响以及耐药结核分枝杆菌（Mtb）菌株的出现，都促使人们寻求针对结核病的改良疫苗。对Mtb疫苗抗原的最低要求是它们在Mtb感染期间的体内表达以及触发明显免疫反应的能力。最近，我们鉴定了一类新的Mtb抗原，称为IVE-TB（体内表达）抗原。其中包括Rv2034，Rv2034是一种在肺部感染过程中表达并被人类T细胞强烈识别的蛋白质。在这里，使用缺乏内源性鼠类MHC II类分子的HLA-DR转基因小鼠进一步分析了Rv2034的体内免疫原性和保护功效。 Rv2034蛋白确实在HLA-DR3转基因小鼠中具有高度免疫原性，并诱导了HLA-DR3限制的IFN-γ+ / TNF +和IFN-γ+ CD4 + T细胞，它们对肽31-50中编码的表位具有特异性。当使用TLR9-和TLR3-配体佐剂或CAF09时，可最佳诱导CD4 + T细胞应答。用TLR2-，TLR3-，TLR4-，TLR5-，TLR7-或TLR9-配体或CAF09免疫后，观察到Rv2034-特异性抗体。重要的是，与未接种疫苗的对照相比，用Rv2034或佐以CpG或CAF09的杂合蛋白Ag85B-ESAT6-Rv2034进行的免疫诱导了Mtb攻击的HLA-DR3转基因小鼠和几内亚肺部细菌数量减少了一个对数猪。这些数据证明了Rv2034作为一种新的IVE-TB抗原在未来结核病疫苗接种中的潜力。

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