A novel liposome adjuvant DPC mediates Mycobacterium tuberculosis subunit vaccine well to induce cell-mediated immunity and high protective efficacy in mice
A novel liposome adjuvant DPC mediates Mycobacterium tuberculosis subunit vaccine well to induce cell-mediated immunity and high protective efficacy in mice
复制标题
新型脂质体佐剂DPC能很好地介导结核分枝杆菌亚单位疫苗，诱导细胞介导的免疫，并在小鼠中具有较高的保护功效
DOI：
10.1016/j.vaccine.2016.01.049
复制
发表时间：
2016-03-08
期刊：
影响因子：
5.5
通讯作者：
Zhu, Bingdong
中科院分区：
文献类型：
--
作者：
Liu, Xun;Da, Zejiao;Zhu, Bingdong
结核病（TB）是世界性的严重疾病，蛋白质亚单位疫苗被认为是一种很有前途的新型结核病疫苗，但目前临床上还没有有效的佐剂来激活TB亚单位疫苗所需的细胞免疫应答。因此，开发新的佐剂势在必行。本文报道了一种由二甲基二十八烷基环铵（DDA）、聚I：C和胆固醇组成的佐剂（简称DPC）。DDA可形成具有抗原递呈能力的阳离子脂质体，并可诱导Th 1型细胞介导的免疫应答。TLR 3受体的配体Poly I：C能减轻结核分枝杆菌攻击后引起的病理反应。在DDA和Poly I：C中加入胆固醇，可以增加脂质双层的刚性，以提高佐剂的稳定性。在体外分析DPC的粒径和Zeta电位。此外，DPC与TB融合蛋白ESAT 6-Ag 85 B-MPT 64（190-198）-Mtb8.4-Rv 2626 c（LT 70）混合以构建亚单位疫苗。亚单位疫苗诱导的免疫应答和保护效果。结核病H37 Rv感染C57 BL/6小鼠。结果表明，粒径为400 nm，zeta电位为40 mV的DPC佐剂稳定性较好。DPC佐剂中的LT 70产生了较强的抗原特异性体液免疫和细胞免疫，并诱导了对M.在接种后30周，结核病感染（5.41 +/- 0.38 log（10）CFU）比传统疫苗卡介苗（BCG）（6.01 +/- 0.33 log（10）CFU）和PBS对照（6.53 +/- 0.26 log（10）CFU）更显著。结论：DPC具有刺激Th 1型细胞免疫的能力，是一种很有前景的疫苗佐剂，可用于结核病亚单位疫苗的研制。(C)2016爱思唯尔有限公司版权所有
Tuberculosis (TB) is a serious disease around the world, and protein based subunit vaccine is supposed to be a kind of promising novel vaccine against it. However, there is no effective adjuvant available in clinic to activate cell-mediated immune responses which is required for TB subunit vaccine. Therefore, it is imperative to develop new adjuvant. Here we reported an adjuvant composed of dimethyl dioctade-cylammonium (DDA), Poly I:C and cholesterol (DPC for short). DDA can form a kind of cationic liposome with the ability to deliver and present antigen and can induce Th1 type cell-mediated immune response. Poly I:C, a ligand of TLR3 receptor, could attenuate the pathologic reaction induced by following Mycobacterium tuberculosis challenge. Cholesterol, which could enhance rigidity of lipid bilayer, is added to DDA and Poly I:C to improve the stability of the adjuvant. The particle size and Zeta-potential of DPC were analyzed in vitro. Furthermore, DPC was mixed with a TB fusion protein ESAT6-Ag85B-MPT64(190-198)-Mtb8.4-Rv2626c (LT70) to construct a subunit vaccine. The subunit vaccine-induced immune responses and protective efficacy against M. tuberculosis H37Rv infection in C57BL/6 mice were investigated. The results showed that the DPC adjuvant with particle size of 400 nm and zeta potential of 40 mV was in good stability. LT70 in the adjuvant of DPC generated strong antigen-specific humoral and cell mediated immunity, and induced long-term higher protective efficacy against M. tuberculosis infection (5.41 +/- 0.38 log(10) CFU) than traditional vaccine Bacillus Calmette-Guerin (BCG) (6.01 +/- 0.33 log(10) CFU) and PBS control (6.53 +/- 0.26 log(10) CFU) at 30 weeks post-vaccination. In conclusion, DPC would be a promising vaccine adjuvant with the ability to stimulate Th1 type cell-mediated immunity, and could be used in TB subunit vaccine. (C) 2016 Elsevier Ltd. All rights reserved.