Priming but not boosting with plasmid DNA encoding mycolyl-transferase Ag85A from Mycobacterium tuberculosis increases the survival time of Mycobacterium bovis BCG vaccinated mice against low dose intravenous challenge with M tuberculosis H37Rv
Priming but not boosting with plasmid DNA encoding mycolyl-transferase Ag85A from Mycobacterium tuberculosis increases the survival time of Mycobacterium bovis BCG vaccinated mice against low dose intravenous challenge with M tuberculosis H37Rv
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DOI：
10.1016/j.vaccine.2005.12.066
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发表时间：
2006-04-12
期刊：
影响因子：
5.5
通讯作者：
Huygen, K
中科院分区：
文献类型：
--
作者：
Romano, M;D'Souza, S;Huygen, K
DNA疫苗接种是诱导小鼠产生强CD 4（+）（Th 1），特别是CD 8（+）介导的免疫反应和针对结核病感染的保护性免疫的有效手段。在这里，我们分析了编码免疫显性分枝杆菌转移酶Ag 85 A的DNA疫苗在三个长期生存实验中增加当前结核病疫苗牛分枝杆菌卡介苗（BCG）的效力的潜力。BALB/c小鼠在DNA引发之后或在DNA加强之前用BCG接种。Ag 85 A特异性CD 4（+）和CD 8（+）介导的IFN-γ应答在BCG之前用DNA致敏的小鼠中增加，并且在BCG接种的小鼠中随后用DNA加强。在后一种免疫方案中，抗原刺激也诱导显著水平的IL-17。监测小鼠的恶病质和低剂量M静脉内攻击后的存活率。结核病H37 Rv.用Ag 85 A而不是对照DNA引发显著增加了BCG疫苗的保护效力，如恶病质减少和存活时间延长所示：在一个实验中为32周对23周，在另一个实验中为33周对26周（对照中的MST，TB感染的小鼠：在两个实验中均为17周）。另一方面，通过随后的盐水或vaxfectin（TM）中的Ag 85 A DNA-或重组85 A蛋白或MVA-85 A（就此而言）-加强BCG并不增加BCG的效力（所有接种组中的MST 19-21周，而对照、TB感染小鼠中的MST 11周）。我们的研究结果表明，Ag 85 A DNA引发可以增加BCG的效力，并且BCG的加强方案可能会受到蒂尔-17细胞诱导的阻碍。(c)2006爱思唯尔有限公司保留所有权利。
DNA vaccination is a potent means for inducing strong CD4(+) (Th1) and particularly CD8(+) mediated immune responses and protective immunity against tuberculosis infection in mice. Here we have analyzed the potential of a DNA vaccine encoding the immunodominant mycolyl-transferase Ag85A for increasing the efficacy of the current tuberculosis vaccine Mycobacterium bovis Bacille Calmette-Guerin (BCG) in three long-term survival experiments. BALB/c mice were vaccinated with BCG either following DNA priming or prior to DNA boosting. Ag85A specific CD4(+) and CD8(+) mediated IFN-gamma responses were increased in mice primed with DNA prior to BCG, and in BCG vaccinated mice subsequently boosted with DNA. In the latter immunization protocol, antigenic stimulation also induced significant levels of IL-17. Mice were monitored for cachexia and survival following a low dose intravenous challenge with M. tuberculosis H37Rv. Priming with Ag85A but not control DNA increased significantly the protective efficacy of the BCG vaccine as indicated by reduced cachexia and prolonged survival time: 32 weeks versus 23 weeks in one experiment and 33 weeks versus 26 weeks in another experiment (MST in control, TB infected mice: 17 weeks in both experiments). On the other hand, boosting of BCG by subsequent Ag85A DNA in saline or vaxfectin (TM)-or recombinant 85A protein or MVA-85A for that matter - did not augment the efficacy of BCG (MST 19-21 weeks in all vaccinated groups versus 11 weeks in control, TB infected mice). Our results demonstrate that Ag85A DNA priming can increase efficacy of BCG and that boosting protocols of BCG may possibly be hampered by the induction of ThIL-17 cells. (c) 2006 Elsevier Ltd. All rights reserved.