Baldwin Susan L, Reese Valerie A, Huang Po-Wei D, Beebe Elyse A, Podell Brendan K, Reed Steven G, Coler Rhea N
Infectious Disease Research Institute, Seattle, Washington, USA
Infectious Disease Research Institute, Seattle, Washington, USA.
Clin Vaccine Immunol. 2015 Dec 9;23(2):137-47. doi: 10.1128/CVI.00458-15. Print 2016 Feb.
Mycobacterium tuberculosis HN878 represents a virulent clinical strain from the W-Beijing family, which has been tested in small animal models in order to study its virulence and its induction of host immune responses following infection. This isolate causes death and extensive lung pathology in infected C57BL/6 mice, whereas lab-adapted strains, such as M. tuberculosis H37Rv, do not. The use of this clinically relevant isolate of M. tuberculosis increases the possibilities of assessing the long-lived efficacy of tuberculosis vaccines in a relatively inexpensive small animal model. This model will also allow for the use of knockout mouse strains to critically examine key immunological factors responsible for long-lived, vaccine-induced immunity in addition to vaccine-mediated prevention of pulmonary immunopathology. In this study, we show that the ID93/glucopyranosyl lipid adjuvant (GLA)-stable emulsion (SE) tuberculosis vaccine candidate, currently in human clinical trials, is able to elicit protection against M. tuberculosis HN878 by reducing the bacterial burden in the lung and spleen and by preventing the extensive lung pathology induced by this pathogen in C57BL/6 mice.
结核分枝杆菌HN878是一株来自W-北京家族的强毒临床菌株,已在小动物模型中进行测试,以研究其毒力以及感染后对宿主免疫反应的诱导作用。该分离株可导致感染的C57BL/6小鼠死亡并引发广泛的肺部病变,而实验室适应株,如结核分枝杆菌H37Rv则不会。使用这种具有临床相关性的结核分枝杆菌分离株增加了在相对廉价的小动物模型中评估结核病疫苗长期疗效的可能性。该模型还将允许使用基因敲除小鼠品系,除了疫苗介导的预防肺部免疫病理学外,还能严格检查负责长期疫苗诱导免疫的关键免疫因素。在本研究中,我们表明目前正在进行人体临床试验的ID93/吡喃葡萄糖基脂质佐剂(GLA)稳定乳剂(SE)结核疫苗候选物能够通过降低肺和脾中的细菌载量以及预防该病原体在C57BL/6小鼠中诱导的广泛肺部病变来诱导对结核分枝杆菌HN878的保护作用。