Shin Hyun-Jin, Franco Luis H, Nair Vidhya R, Collins Angela C, Shiloh Michael U
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States of America.
Center for Autophagy Research, University of Texas Southwestern Medical Center, Dallas, TX, United States of America.
PLoS One. 2017 Oct 5;12(10):e0185945. doi: 10.1371/journal.pone.0185945. eCollection 2017.
Mycobacterium tuberculosis, the causative agent of tuberculosis, is a major cause of morbidity and mortality worldwide. However, an effective vaccine for M. tuberculosis is lacking. We panned a phage display library using monoclonal antibodies against M. tuberculosis liporabinomannan (LAM), an important component of the M. tuberculosis cell wall, and identified two peptide sequences, HSFKWLDSPRLR or SGVYKVAYDWQH, with high antibody affinity after multiple rounds of panning. Only the HSFKWLDSPRLR peptide induced an anti-LAM response when conjugated to either keyhole limpet hemocyanin (KLH) or to the baculovirus Autographa californica multicapsid nucleopolyherovirus (AcMNPV) when introduced into mice by injection or via intranasal inoculation, respectively. Vaccination with AcMNPV conjugated HSFKWLDSPRLR peptide delayed mortality in a mouse model of tuberculosis. Thus, we report a proof of principle M. tuberculosis vaccination strategy combining an anti-LAM mimotope with a baculovirus delivery system.
结核分枝杆菌是结核病的病原体，是全球发病和死亡的主要原因。然而，目前缺乏针对结核分枝杆菌的有效疫苗。我们使用针对结核分枝杆菌脂阿拉伯甘露聚糖（LAM，结核分枝杆菌细胞壁的重要组成部分）的单克隆抗体筛选噬菌体展示文库，并在多轮筛选后鉴定出两个具有高抗体亲和力的肽序列，HSFKWLDSPRLR或SGVYKVAYDWQH。当分别与匙孔血蓝蛋白（KLH）或杆状病毒苜蓿银纹夜蛾多角体核型多角体病毒（AcMNPV）偶联时，只有HSFKWLDSPRLR肽在通过注射或经鼻内接种引入小鼠后诱导了抗LAM反应。用AcMNPV偶联的HSFKWLDSPRLR肽进行疫苗接种可延缓结核病小鼠模型中的死亡。因此，我们报告了一种将抗LAM模拟表位与杆状病毒递送系统相结合的结核分枝杆菌疫苗接种策略的原理验证。
