TY - JOUR
T1 - Multi-stage tuberculosis subunit vaccine candidate LT69 provides high protection against Mycobacterium tuberculosis infection in mice
AU - Niu, Hongxia
AU - Peng, Jinxiu
AU - Bai, Chunxiang
AU - Liu, Xun
AU - Hu, Lina
AU - Luo, Yanping
AU - Wang, Bingxiang
AU - Zhang, Ying
AU - Chen, Jianzhu
AU - Yu, Hongjuan
AU - Xian, Qiaoyang
AU - Zhu, Bingdong
N1 - Publisher Copyright:
© 2015 Niu et al.
PY - 2015/6/22
Y1 - 2015/6/22
N2 - 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 multistage 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.
AB - 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 multistage 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.
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U2 - 10.1371/journal.pone.0130641
DO - 10.1371/journal.pone.0130641
M3 - Article
C2 - 26098302
AN - SCOPUS:84939155409
SN - 1932-6203
VL - 10
JO - PloS one
JF - PloS one
IS - 6
M1 - e0130641
ER -