Protection associated with a TB vaccine is linked to increased frequency of Ag85A-specific CD4(+) T cells but no increase in avidity for Ag85A.
Protection associated with a TB vaccine is linked to increased frequency of Ag85A-specific CD4(+) T cells but no increase in avidity for Ag85A.
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DOI：
10.1016/j.vaccine.2016.07.055
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发表时间：
2016-08-31
期刊：
影响因子：
5.5
通讯作者：
Villarreal-Ramos B
中科院分区：
文献类型：
--
作者：
Metcalfe HJ;Steinbach S;Jones GJ;Connelley T;Morrison WI;Vordermeier M;Villarreal-Ramos B
BCG-Ad5-85A保护作用与更高的CD4+ ag85a特异性细胞频率相关。BCG-Ad5-85A保护与CD4+ ag85a特异性贪婪度的增加无关。BCG-Ad5-85A的保护作用与表位扩散无关。有必要提高卡介苗（Bacille calmette - gusamrin， BCG）预防人类和牛结核病的效力。先前，我们发现，与单独接种BCG相比，用表达抗原85A的重组人5型腺病毒（Ad5-85A）增强BCG引奶牛对牛分枝杆菌感染的保护作用增强。这项研究的目的是破译与这种增强保护有关的免疫反应的各个方面。我们比较了bcg引物ad5 - 85a增强牛与bcg接种牛。使用Geiger等人（2009）的方法，从增强前和增强后的外周血单个核细胞中生成多克隆CD4+ T细胞文库，并筛选抗原85A （Ag85A）特异性。分析Ag85A特异性CD4+ T细胞系对Ag85A的亲和力，并确定其Ag85A表位特异性。用Ad5-85A增强BCG增加了增强后ag85a特异性CD4+ T细胞的频率，这与保护（减少病理）相关。增强ag85a特异性CD4+ T细胞反应并没有增加它们的贪婪度。表位特异性在不同的动物之间是可变的，我们没有发现明显的证据表明促进后表位扩散。总之，用Ad5-85A增强BCG的保护作用与ag85a特异性CD4+ T细胞的频率增加有关，而不会增加ag85a特异性CD4+ T细胞的数量或扩大。
BCG-Ad5-85A protection was associated with higher CD4+ Ag85A-specific cell frequency. BCG-Ad5-85A protection was not associated with increased CD4+ Ag85A-specific avidity. BCG-Ad5-85A protection was not associated with epitope spreading. There is a need to improve the efficacy of Bacille Calmette-Guérin (BCG) vaccination against tuberculosis in humans and cattle. Previously, we found boosting BCG-primed cows with recombinant human type 5 adenovirus expressing antigen 85A (Ad5-85A) increased protection against Mycobacterium bovis infection compared to BCG vaccination alone. The aim of this study was to decipher aspects of the immune response associated with this enhanced protection. We compared BCG-primed Ad5-85A-boosted cattle with BCG-vaccinated cattle. Polyclonal CD4+ T cell libraries were generated from pre-boost and post-boost peripheral blood mononuclear cells – using a method adapted from Geiger et al. (2009) – and screened for antigen 85A (Ag85A) specificity. Ag85A-specific CD4+ T cell lines were analysed for their avidity for Ag85A and their Ag85A epitope specificity was defined. Boosting BCG with Ad5-85A increased the frequencies of post-boost Ag85A-specific CD4+ T cells which correlated with protection (reduced pathology). Boosting Ag85A-specific CD4+ T cell responses did not increase their avidity. The epitope specificity was variable between animals and we found no clear evidence for a post-boost epitope spreading. In conclusion, the protection associated with boosting BCG with Ad5-85A is linked with increased frequencies of Ag85A-specific CD4+ T cells without increasing avidity or widening of the Ag85A-specific CD4+ T cell repertoire.
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影响因子：
32.4
作者：
Honda T;Egen JG;Lämmermann T;Kastenmüller W;Torabi-Parizi P;Germain RN
通讯作者：
Germain RN
影响因子：
4.4
作者：
Lindenstrom, Thomas;Knudsen, Niels Peter Hell;Andersen, Peter
通讯作者：
Andersen, Peter
影响因子：
11.6
作者：
Noonan, Michael J.;Rahman, M. Abidur;Macdonald, David W.
通讯作者：
Macdonald, David W.
DOI：
10.1098/rstb.2011.0097
发表时间：
2011-10-12
期刊：
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
影响因子：
--
作者：
McShane H
通讯作者：
McShane H
影响因子：
30.5
作者：
Gallegos AM;Xiong H;Leiner IM;Sušac B;Glickman MS;Pamer EG;van Heijst JW
通讯作者：
van Heijst JW