Multi-Stage Tuberculosis Subunit Vaccine Candidate LT69 Provides High Protection against Mycobacterium tuberculosis Infection in Mice.

Multi-Stage Tuberculosis Subunit Vaccine Candidate LT69 Provides High Protection against Mycobacterium tuberculosis Infection in Mice.
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多阶段结核亚单位候选疫苗 LT69 为小鼠提供针对结核分枝杆菌感染的高度保护

DOI:
10.1371/journal.pone.0130641
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Zhu B
Zhu B
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Niu H;Peng J;Bai C;Liu X;Hu L;Luo Y;Wang B;Zhang Y;Chen J;Yu H;Xian Q;Zhu B

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有效的结核病(TB)疫苗应针对不同代谢状态的结核杆菌,并赋予长期的保护性免疫。本研究以ESAT 6-Ag 85 B-MPT 64(190-198)-Mtb8.4-HspX融合蛋白(简称LT 69)为基础,结合早期表达抗原和潜伏相关抗原,构建了一种新型多阶段结核亚单位疫苗。将该融合蛋白与N,N '-二甲基-N,N'-双十八烷基溴化铵(DDA)和多聚核糖肌苷酸(PolyI:C)组成的佐剂混合,构建亚单位疫苗,并在C57 BL/6小鼠体内进行免疫原性和保护力评价。结果表明,LT 69具有较强的免疫原性,对结核分枝杆菌(M. H37 Rv气溶胶攻击。低剂量(2 μg)的LT 69产生长期免疫记忆应答并提供有效保护,其在最后一次接种后30周时甚至高于传统疫苗BCG。总之,多阶段亚单位疫苗LT 69对M.结核杆菌感染小鼠,其效果可以通过使用相对低剂量的抗原而增强。
Effective tuberculosis (TB) vaccine should target tubercle bacilli with various metabolic states and confer long-term protective immunity. In this study, we constructed a novel multi-stage TB subunit vaccine based on fusion protein ESAT6-Ag85B-MPT64(190-198)-Mtb8.4-HspX (LT69 for short) which combined early expressed antigens and latency-associated antigen. The fusion protein was mixed with an adjuvant being composed of N, N’-dimethyl-N, N’-dioctadecylammonium bromide (DDA) and polyriboinosinic polyribocytidylic acid (PolyI:C) to construct subunit vaccine, whose immunogenicity and protective ability were evaluated in C57BL/6 mice. The results showed that LT69 had strong immunogenicity and high protective effect against Mycobacterium tuberculosis (M. tuberculosis) H37Rv aerosol challenge. Low-dose (2 μg) of LT69 generated long-term immune memory responses and provided effective protection, which was even higher than traditional vaccine BCG did at 30 weeks post the last vaccination. In conclusion, multistage subunit vaccine LT69 showed high and long-term protection against M. tuberculosis infection in mice, whose effect could be enhanced by using a relative low dosage of antigen.
DOI: 10.1371/journal.pone.0039909
发表时间: 2012
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影响因子: 3.7
作者:
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由多级抗原组成的亚单位疫苗对小鼠结核分枝杆菌感染具有较高的保护效力。
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发表时间: 2013
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影响因子: 3.7
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