Reactivation of immune responses against Mycobacterium tuberculosis by boosting with the CpG oligomer in aged mice primarily vaccinated with Mycobacterium bovis BCG.
Reactivation of immune responses against Mycobacterium tuberculosis by boosting with the CpG oligomer in aged mice primarily vaccinated with Mycobacterium bovis BCG.
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DOI：
10.1186/1742-4933-10-25
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发表时间：
2013-06-22
期刊：
影响因子：
--
通讯作者：
Onozaki K
中科院分区：
文献类型：
--
作者：
Taniguchi K;Takii T;Yamamoto S;Maeyama J;Iho S;Maruyama M;Iizuka N;Ozeki Y;Matsumoto S;Hasegawa T;Miyatake Y;Itoh S;Onozaki K
牛分枝杆菌卡介苗(BCG)已在全球10多亿人中接种，对预防新生儿和婴幼儿的结核性脑膜炎和粟粒结核病有显著的效果。然而，卡介苗未能充分预防肺结核病和成人潜伏感染的重新激活。为了克服这一问题，迫切需要在接受过卡介苗接种的成人中使用足够的加强剂，而合适的动物模型替代人类病例将对进一步的实验具有很高的价值。合成的CpG寡聚体(Origo-B)对4周龄初次接种卡介苗的老龄小鼠的免疫增强作用。特异性Th1型反应、干扰素-γ的产生、对结核抗原的反应、纯化蛋白衍生物和对结核分枝杆菌H37Rv攻击的保护作用随着年龄的增长而降低，在89周龄的小鼠中未观察到。为了恢复对PPD的Th1型应答和对结核分枝杆菌感染的保护作用，对81~90周龄的小鼠(相当于人类50岁晚期的S)在4周龄接种卡介苗后，给予已知的增强Th1应答的寡糖B作为增强剂。低聚糖B增强后，小鼠外周血中CD4+CD44High、CD62LHigh、中央记忆型T细胞数量增加。此外，寡聚-B增强恢复了小鼠抵抗结核分枝杆菌H37Rv感染的能力。Th1佐剂CpG寡聚DNA，如Origo-B，当与卡介苗启动时，可能是一种有前途的增强剂。
Mycobacterium bovis bacillus Calmette Guérin (BCG) vaccine, which has been inoculated to more than one billion people world-wide, has significant effect in preventing tuberculous meningitis and miliary tuberculosis (TB) in neonate and early childhood. However, BCG fails to adequately protect against pulmonary TB and reactivation of latent infections in adults. To overcome this problem, adequate booster is urgently desired in adult who received prior BCG vaccination, and appropriate animal models that substitute human cases would be highly valuable for further experimentation. The booster effect of the synthesized CpG oligomer (Oligo-B) on aged mice which had been primarily vaccinated with BCG at the age of 4-week old. The specific Th1 type reaction, production of interferon-γ, in response to TB antigens, purified protein derivatives (PPD) and protection against challenge with Mycobacterium tuberculosis (MTB) H37Rv decreased with increasing age and were not observed in 89-week old mice. In order to rejuvenate the Th1 type response against PPD and protection activity against MTB infection, Oligo-B, which is known to augment Th1 responses, was administered as a booster to 81-90-week old mice (late 50’s in human equivalent) vaccinated with BCG at 4-week old. The boosting with Oligo-B increased the number of CD4+ CD44high CD62Lhigh, central memory type T cell. Furthermore, the Oligo-B boosting rejuvenated the ability of mice to protect against infection with MTB H37Rv. Th1-adjuvant CpG oligo DNA, such as Oligo-B, may be a promising booster when coupled with BCG priming.
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影响因子：
15.9
作者：
Ito, Toshihiro;Schaller, Matthew;Kunkel, Steven L.
通讯作者：
Kunkel, Steven L.
DOI：
10.1186/1742-4933-7-12
发表时间：
2010-09-01
期刊：
Immunity & ageing : I & A
影响因子：
--
作者：
Ito T;Takii T;Maruyama M;Hayashi D;Wako T;Asai A;Horita Y;Taniguchi K;Yano I;Yamamoto S;Onozaki K
通讯作者：
Onozaki K
影响因子：
4.4
作者：
Lindenstrom, Thomas;Agger, Else Marie;Andersen, Peter
通讯作者：
Andersen, Peter
影响因子：
5.5
作者：
Ballester, Marie;Nembrini, Chiara;Swartz, Melody A.
通讯作者：
Swartz, Melody A.
影响因子：
2.6
作者：
YAMAMOTO, S;YAMAMOTO, T;TOKUNAGA, T
通讯作者：
TOKUNAGA, T