Innate immunity for biodefense: a strategy whose time has come.
Innate immunity for biodefense: a strategy whose time has come.
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DOI：
10.1016/j.jaci.2005.08.048
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发表时间：
2005-12
期刊：
影响因子：
--
通讯作者：
Whelan HT
中科院分区：
文献类型：
--
作者：
Amlie-Lefond C;Paz DA;Connelly MP;Huffnagle GB;Whelan NT;Whelan HT
防御生物威胁剂需要一种广谱方法。先天免疫系统的调节可能满足这一要求。Hackett之前对先天免疫激活作为广谱生物防御策略的回顾发现了几个尚未解决的问题。目前的文章是一个系统的方法来回答这些问题，重点参与研究小组开发这项技术。我们的学术和行业参与者团队审查了有前途的药物，并得出以下结论。在保守的微生物成分的基础上，通过鼻腔喷雾剂激活呼吸道和胃肠道的免疫，构建一个联合协同剂激活先天免疫系统对抗多种病原体的生物防御平台是可行的，因为呼吸道和胃肠道是最可能的攻击途径。也可能包括抑制导致感染性休克的分子事件的药物。设计用于激活toll样受体和其他受体的先天免疫激活剂可能会对生物威胁病原体谱提供保护，时间范围从ifn的2至14天到免疫调节寡核苷酸的26周。初步治疗建议在第一个指标病例或生物传感器警报。需要增加剂量。有害的炎症是可能的，但到目前为止，只观察到短暂的发烧。到目前为止，在许多这些化合物的临床前和人体试验中尚未看到自身免疫反应和逆转录病毒激活。toll样受体激动剂在所有受试者中都引起细胞因子的产生，但遗传多态性降低了非裔美国受试者对IFN的反应。
Defense against biothreat agents requires a broad-spectrum approach. Modulation of the innate immune system might fulfill this requirement. Hackett's previous review of innate immune activation as a broad-spectrum biodefense strategy identified several unresolved questions. The current article is a systematic approach to answering those questions with the focused participation of research groups developing this technology. Our team of academic and industry participants reviewed the promising agents and came to the following conclusions. It is feasible to construct a biodefense platform combining synergistic agents that activate the innate immune system against a broad range of pathogens on the basis of conserved microbial components by using a nasal spray for immune activation in the respiratory and gastrointestinal tracts because these are the most likely routes of attack. It might also be possible to include agents that inhibit molecular events leading to septic shock. Innate immune-activating agents designed to activate Toll-like and other receptors will probably provide protection against the biothreat pathogen spectrum for periods ranging from 2 to 14 days for IFNs up to 26 weeks for immunomodulatory oligonucleotides. Initial treatment is proposed on the first index case or biosensor alert. Boost doses would be required. Harmful inflammation is possible, but thus far, only transient fever has been observed. Autoimmune reaction and retroviral activation have not been seen thus far in preclinical and human trials of many of these compounds. Toll-like receptor agonists caused cytokine production in all subjects tested, but genetic polymorphism reduced the response to IFN in African American subjects.
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影响因子：
4.8
作者：
Stöver, AG;Correia, JD;Hershberg, RM
通讯作者：
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DOI：
10.1165/rcmb.2003-0388oc
发表时间：
2004-09-01
影响因子：
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作者：
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含热溶解CpG的DNA寡核苷酸作为潜在的免疫治疗前药。
影响因子：
14.9
作者：
Grajkowski, A;Pedras-Vasconcelos, J;Wang, VV;Ausín, C;Hess, S;Verthelyi, D;Beaucage, SL
通讯作者：
Beaucage, SL