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首页> 外文期刊>Infection and immunity >Immunogenicity and Protective Efficacy of Prime-Boost Regimens with Recombinant ΔureC hly+ Mycobacterium bovis BCG and Modified Vaccinia Virus Ankara Expressing M. tuberculosis Antigen 85A against Murine Tuberculosis
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Immunogenicity and Protective Efficacy of Prime-Boost Regimens with Recombinant ΔureC hly+ Mycobacterium bovis BCG and Modified Vaccinia Virus Ankara Expressing M. tuberculosis Antigen 85A against Murine Tuberculosis

机译：重组ΔureChly +牛分枝杆菌BCG和修饰的痘苗病毒安卡拉表达初生-加强型疫苗的免疫原性和保护功效，表达抗结核分枝杆菌抗原85A。

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In the light of the recent emergence of multidrug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis, the epidemic of tuberculosis (TB) in populations coinfected with human immunodeficiency virus, and the failure of Mycobacterium bovis bacillus Calmette-Guerin (BCG) to protect against disease, new vaccines against TB are urgently needed. Two promising new vaccine candidates are the recombinant ΔureC hly+ BCG (recBCG), which has been developed to replace the current BCG vaccine strain, and modified vaccinia virus Ankara (MVA) expressing M. tuberculosis antigen 85A (MVA85A), which is a leading candidate vaccine designed to boost the protective efficacy of BCG. In the present study, we examined the effect of MVA85A boosting on the protection afforded at 12 weeks postchallenge by BCG and recBCG by using bacterial CFU as an efficacy readout. recBCG-immunized mice were significantly better protected against aerosol challenge with M. tuberculosis than mice immunized with the parental strain of BCG. Intradermal boosting with MVA85A did not reduce the bacterial burden any further. In order to identify a marker for the development of a protective immune response against M. tuberculosis challenge, we analyzed splenocytes after priming or prime-boosting by using intracytoplasmic cytokine staining and assays for cytokine secretion. Boosting with MVA85A, but not priming with BCG or recBCG, greatly increased the antigen 85A-specific T-cell response, suggesting that the mechanism of protection may differ from that against BCG or recBCG. We show that the numbers of systemic multifunctional cytokine-producing cells did not correlate with protection against aerosol challenge in BALB/c mice. This emphasizes the need for new biomarkers for the evaluation of TB vaccine efficacy.
机译：鉴于最近出现了对结核分枝杆菌具有多重耐药性和广泛耐药性的菌株，在合并了人类免疫缺陷病毒的人群中结核病（TB）流行以及的失败牛分枝杆菌卡介苗（BCG）可以预防疾病，因此迫切需要新的抗结核疫苗。两种有希望的新疫苗候选物是重组Δ ureC hly + BCG（recBCG）（已开发以替代当前的BCG疫苗株）和改良的牛痘病毒安卡拉（MVA） ）表示 M。结核抗原85A（MVA85A）是旨在增强卡介苗保护作用的领先候选疫苗。在本研究中，我们通过使用细菌CFU作为功效指标，研究了MVA85A增强对BCG和recBCG攻击后12周提供的保护作用。 recBCG免疫的小鼠对 M的气溶胶攻击具有更好的保护作用。比用BCG亲本株免疫的小鼠高。用MVA85A进行皮内加强治疗不会进一步减轻细菌负担。为了鉴定针对 M的保护性免疫应答的发展的标志物。在结核病挑战中，我们通过使用胞浆内细胞因子染色和细胞因子分泌分析法分析了引发或增强免疫后的脾细胞。用MVA85A加强免疫，但不使用BCG或recBCG引发，大大增加了抗原85A特异的T细胞反应，这表明其保护机制可能不同于针对BCG或recBCG的保护机制。我们显示系统性多功能细胞因子产生细胞的数量与在BALB / c小鼠中对抗气溶胶攻击的保护作用不相关。这强调了需要新的生物标志物来评估结核病疫苗效力。

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