Adult-like anti-mycobacterial T cell and in vivo dendritic cell responses following neonatal immunization with Ag85B-ESAT-6 in the IC31 adjuvant.
Adult-like anti-mycobacterial T cell and in vivo dendritic cell responses following neonatal immunization with Ag85B-ESAT-6 in the IC31 adjuvant.
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IC31辅助物中新生儿免疫后使用AG85B-ESAT-6进行新生儿免疫后，成人样的抗菌T细胞和体内树突状细胞反应。
DOI：
10.1371/journal.pone.0003683
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发表时间：
2008
期刊：
影响因子：
3.7
通讯作者：
Siegrist, Claire-Anne
中科院分区：
文献类型：
--
作者：
Kamath, Arun T.;Rochat, Anne-Francoise;Valenti, Mario P.;Agger, Else Marie;Lingnau, Karen;Andersen, Peter;Lambert, Paul-Henri;Siegrist, Claire-Anne
除了一些活疫苗，例如BCG，用“经典”佐剂配制的亚单位疫苗在新生儿中不诱导与成人相似的应答。通常的新生儿特征是TH 1相关生物标志物水平较低。这阻碍了为需要早期保护的疾病开发新的新生儿疫苗。结核病是新生儿免疫接种的主要目标之一。在这项研究中，我们评估了一种新的候选疫苗，包括分枝杆菌融合蛋白，Ag 85 B-ESAT-6，在新生鼠免疫模型的免疫原性。Ag 85 B-ESAT-6融合蛋白与经典的基于明矾的佐剂或与新型IC 31 ®佐剂一起配制。在新生儿或成人免疫后，在体内研究了3个参数：（1）CD 4 + T细胞应答，（2）树突状细胞（DC）的疫苗靶向/活化和（3）在替代分枝杆菌攻击模型中的保护。与明矾相反，IC 31 ®在两个年龄组中诱导了强烈的Th 1和Th 17应答，其特征在于多功能T细胞表达IL-2和TNF-α，有或没有IFN-γ。在引流淋巴结中，在新生儿或成人免疫后，同样少量的DC含有佐剂和/或抗原。CD 40、CD 80、CD 86和IL-12 p40的表达集中在携带促凋亡剂的微小DC群体上。同样，DC靶向/激活在成人和新生儿中相似。这些DC/T细胞应答导致感染M后细菌生长的等效减少。牛BCG时，而明矾作为佐剂时没有观察到保护作用。用含IC 31 ®佐剂的Ag 85 B-ESAT-6亚单位疫苗进行新生儿免疫接种通过诱导体内DC活化的成人模式引发成人样多功能保护性抗分枝杆菌T细胞应答。
With the exception of some live vaccines, e.g. BCG, subunit vaccines formulated with “classical” adjuvants do not induce similar responses in neonates as in adults. The usual neonatal profile is characterized by lower levels of TH1-associated biomarkers. This has hampered the development of new neonatal vaccines for diseases that require early protection. Tuberculosis is one of the major targets for neonatal immunization. In this study, we assessed the immunogenicity of a novel candidate vaccine comprising a mycobacterial fusion protein, Ag85B-ESAT-6, in a neonatal murine immunization model. The Ag85B-ESAT-6 fusion protein was formulated either with a classical alum based adjuvant or with the novel IC31® adjuvant. Following neonatal or adult immunization, 3 parameters were studied in vivo: (1) CD4+ T cell responses, (2) vaccine targeting/activation of dendritic cells (DC) and (3) protection in a surrogate mycobacterial challenge model. Conversely to Alum, IC31® induced in both age groups strong Th1 and Th17 responses, characterized by multifunctional T cells expressing IL-2 and TNF-α with or without IFN-γ. In the draining lymph nodes, a similarly small number of DC contained the adjuvant and/or the antigen following neonatal or adult immunization. Expression of CD40, CD80, CD86 and IL-12p40 production was focused on the minute adjuvant-bearing DC population. Again, DC targeting/activation was similar in adults and neonates. These DC/T cell responses resulted in an equivalent reduction of bacterial growth following infection with M. bovis BCG, whereas no protection was observed when Alum was used as adjuvant. Neonatal immunization with the IC31®- adjuvanted Ag85B-ESAT-6 subunit vaccine elicited adult-like multifunctional protective anti-mycobacterial T cell responses through the induction of an adult pattern of in vivo DC activation.
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影响因子：
4.4
作者：
Ota, MOC;Vekemans, J;Marchant, A
通讯作者：
Marchant, A
影响因子：
3.6
作者：
Angelone, Donatella F.;Wessels, Michael R.;Levy, Ofer
通讯作者：
Levy, Ofer
DOI：
10.1073/pnas.95.26.15553
发表时间：
1998-12-22
影响因子：
11.1
作者：
Millan, CLB;Weeratna, R;Davis, HL
通讯作者：
Davis, HL
影响因子：
82.9
作者：
Darrah, Patricia A.;Patel, Dipti T.;Seder, Robert A.
通讯作者：
Seder, Robert A.
影响因子：
5.4
作者：
Barrios, C;Brandt, C;Siegrist, CA
通讯作者：
Siegrist, CA