Subunit vaccine consisting of multi-stage antigens has high protective efficacy against Mycobacterium tuberculosis infection in mice.
Subunit vaccine consisting of multi-stage antigens has high protective efficacy against Mycobacterium tuberculosis infection in mice.
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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。
DOI：
10.1371/journal.pone.0072745
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zhu B
中科院分区：
文献类型：
--
作者：
Xin Q;Niu H;Li Z;Zhang G;Hu L;Wang B;Li J;Yu H;Liu W;Wang Y;Da Z;Li R;Xian Q;Wang Y;Zhang Y;Jing T;Ma X;Zhu B
为了寻找更有效的结核分枝杆菌（M. tuberculosis）亚单位疫苗，选择复苏阶段产生的RpfE （Rv2450c）、主要由复制杆菌分泌的Mtb10.4 （Rv0288）、Mtb8.4 （Rv1174c）、ESAT6 （Rv3875）、Ag85B （Rv1886c）、休眠杆菌中高表达的HspX （Rv2031c）等不同生长阶段表达的抗原，构建6种融合蛋白：ESAT6-Ag85B- mpt64190 -198- mtb8.4 （EAMM）、Mtb10.4-HspX （MH）、ESAT6-Mtb8.4、Mtb10.4-Ag85B、ESAT6-Ag85B、ESAT6-RpfE。将6种融合蛋白分别乳化于N、N′-二甲基-N、N′-二十二烷基溴化铵（DDA）、多核胞酸（poly I:C）和明胶组成的佐剂中，构建亚单位疫苗，并在C57BL/6小鼠中评价其对结核分枝杆菌感染的保护作用。此外，还评价了DDA +海藻糖6,6′-二mycolate （TDM）佐剂中EAMM和MH对bcg诱导免疫的增强作用。结果表明，这6种蛋白在大肠杆菌中稳定产生，并经层析纯化成功。其中，EAMM对M. tuberculosis的保护效果最好。有趣的是，与接种单蛋白疫苗组相比，接种EAMM+MH的小鼠肺和脾脏中的细菌计数明显降低，并且与接种卡介苗的小鼠具有相同的效果。此外，EAMM和MH可提高bcg对小鼠结核分枝杆菌感染的保护作用。综上所述，EAMM和含有复制期和休眠期杆菌抗原的MH结合可以诱导小鼠对结核分枝杆菌感染产生强大的免疫力，可能是有希望的亚单位疫苗候选物。
To search for more effective tuberculosis (TB) subunit vaccines, antigens expressed in different growth stages of Mycobacterium tuberculosis (M. tuberculosis), such as RpfE (Rv2450c) produced in the stage of resuscitation, Mtb10.4 (Rv0288), Mtb8.4 (Rv1174c), ESAT6 (Rv3875), Ag85B (Rv1886c) mainly secreted by replicating bacilli, and HspX (Rv2031c) highly expressed in dormant bacilli, were selected to construct six fusion proteins: ESAT6-Ag85B-MPT64190-198-Mtb8.4 (EAMM), Mtb10.4-HspX (MH), ESAT6-Mtb8.4, Mtb10.4-Ag85B, ESAT6-Ag85B, and ESAT6-RpfE. The six fusion proteins were separately emulsified in an adjuvant composed of N,N’-dimethyl-N, N’-dioctadecylammonium bromide (DDA), polyribocytidylic acid (poly I:C) and gelatin to construct subunit vaccines, and their protective effects against M. tuberculosis infection were evaluated in C57BL/6 mice. Furthermore, the boosting effects of EAMM and MH in the adjuvant of DDA plus trehalose 6,6'-dimycolate (TDM) on BCG-induced immunity were also evaluated. It was found that the six proteins were stably produced in E. coli and successfully purified by chromatography. Among them, EAMM presented the most effective protection against M. tuberculosis. Interestingly, the mice that received EAMM+MH had significantly lower bacterial counts in the lungs and spleens than the single protein vaccinated groups, and had the same effect as those that received BCG. In addition, EAMM and MH could improve BCG-primed protective efficacy against M. tuberculosis infection in mice. In conclusion, the combination of EAMM and MH containing antigens from both replicating and dormant stages of the bacilli could induce robust immunity against M. tuberculosis infection in mice and may serve as promising subunit vaccine candidate.
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影响因子：
3.1
作者：
Downing, KJ;Mischenko, VV;Mizrahi, V
通讯作者：
Mizrahi, V
影响因子：
168.9
作者：
Harries, Anthony D.;Zachariah, Rony;De Cock, Kevin M.
通讯作者：
De Cock, Kevin M.
DOI：
10.1086/590185
发表时间：
2008-08-15
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Hawkridge T;Scriba TJ;Gelderbloem S;Smit E;Tameris M;Moyo S;Lang T;Veldsman A;Hatherill M;Merwe Lv;Fletcher HA;Mahomed H;Hill AV;Hanekom WA;Hussey GD;McShane H
通讯作者：
McShane H
DOI：
10.1084/jem.183.6.2593
发表时间：
1996-06-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fossiez F;Djossou O;Chomarat P;Flores-Romo L;Ait-Yahia S;Maat C;Pin JJ;Garrone P;Garcia E;Saeland S;Blanchard D;Gaillard C;Das Mahapatra B;Rouvier E;Golstein P;Banchereau J;Lebecque S
通讯作者：
Lebecque S
影响因子：
17.1
作者：
Bertholet S;Ireton GC;Ordway DJ;Windish HP;Pine SO;Kahn M;Phan T;Orme IM;Vedvick TS;Baldwin SL;Coler RN;Reed SG
通讯作者：
Reed SG