Therapeutic Immunization against Mycobacterium tuberculosis Is an Effective Adjunct to Antibiotic Treatment
Therapeutic Immunization against Mycobacterium tuberculosis Is an Effective Adjunct to Antibiotic Treatment
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DOI：
10.1093/infdis/jis425
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发表时间：
2013-04-15
影响因子：
6.4
通讯作者：
Reed, Steven G.
中科院分区：
文献类型：
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作者：
Coler, Rhea N.;Bertholet, Sylvie;Reed, Steven G.
背景在合理佐剂设计和抗原选择方面的最新进展使得新一代疫苗具有治疗和预防传染病的潜力。本研究的目的是评估治疗性免疫接种是否可以影响结核分枝杆菌感染的过程，使用候选结核疫苗抗原ID 93，配制在合成纳米乳液佐剂GLA-SE中，与现有的一线化疗药物利福平和异烟肼联合施用。我们使用致死性结核病小鼠模型和已建立的食蟹猴模型设计了一种免疫化疗策略，与单独使用标准抗生素化疗相比，可增加长期生存率并减少细菌负荷。这种联合方法诱导了强大而持久的多能抗原特异性T辅助细胞-1型免疫应答，降低了细菌负荷，减少了生存所需的常规化疗的持续时间，并减少了M。与单纯化疗相比，结核病引起的肺部病理改变。这些结果表明，治疗性免疫接种的能力，显着提高化疗对结核病和其他传染病的疗效，与治疗持续时间，病人的依从性，更优化的资源分配的影响。
Background. Recent advances in rational adjuvant design and antigen selection have enabled a new generation of vaccines with potential to treat and prevent infectious disease. The aim of this study was to assess whether therapeutic immunization could impact the course of Mycobacterium tuberculosis infection with use of a candidate tuberculosis vaccine antigen, ID93, formulated in a synthetic nanoemulsion adjuvant, GLA- SE, administered in combination with existing first- line chemotherapeutics rifampicin and isoniazid.Methods. We used a mouse model of fatal tuberculosis and the established cynomolgus monkey model to design an immuno-chemotherapeutic strategy to increase long-term survival and reduce bacterial burden, compared with standard antibiotic chemotherapy alone.Results. This combined approach induced robust and durable pluripotent antigen-specific T helper-1-type immune responses, decreased bacterial burden, reduced the duration of conventional chemotherapy required for survival, and decreased M. tuberculosis-induced lung pathology, compared with chemotherapy alone.Conclusions. These results demonstrate the ability of therapeutic immunization to significantly enhance the efficacy of chemotherapy against tuberculosis and other infectious diseases, with implications for treatment duration, patient compliance, and more optimal resource allocation.