Hamasur Beston, Haile Melles, Pawlowski Andrzej, Schröder Ulf, Williams Ann, Hatch Graham, Hall Graham, Marsh Philip, Källenius Gunilla, Svenson Stefan B
Swedish Institute for Infectious Disease Control, S-17182 Solna, Sweden.
Vaccine. 2003 Sep 8;21(25-26):4081-93. doi: 10.1016/s0264-410x(03)00274-3.
Lipoarabinomannan (LAM) is a major structural surface component of mycobacteria. Arabinomannan (AM) oligosaccharides derived from LAM of Mycobacterium tuberculosis H37Rv were isolated and covalently conjugated to tetanus toxoid (TT) or to short-term culture filtrate proteins (antigen 85B (Ag85B) or a 75kDa protein) from M. tuberculosis strain Harlingen. The different AM oligosaccharide (AMOs)-protein conjugate vaccine candidates proved to be highly immunogenic, inducing boosterable IgG responses against the AMOs portion of the conjugates in rabbits and guinea-pigs. Proliferation of T-cells from C57BL/6 mice immunized with the conjugates was seen upon in vitro stimulation with PPD. In C57BL/6 mice subcutaneous immunization with the AMOs-antigen 85B conjugate in alum provided significant protection compared to sham (alum only) immunized mice (P < 0.021) as estimated by long term survival against intravenous challenge with 10(5) M. tuberculosis H37Rv. Subcutaneous immunization followed by nasal boost with an AMOs-TT conjugate in Eurocine L3 adjuvant provided high (P < 0.025) protection as determined by long term survival after intranasal challenge with 10(5) virulent M. tuberculosis strain Harlingen. This level of protection was comparable to that obtained with the conventional live attenuated BCG vaccine. In guinea-pigs, immunization with AMOs-Ag85B in Eurocine L3 adjuvant followed by aerogenic challenge with M. tuberculosis H37Rv resulted in increased survival and reduced pathology in lungs and spleens relative to non-immunized animals.
脂阿拉伯甘露聚糖（LAM）是分枝杆菌主要的结构性表面成分。从结核分枝杆菌H37Rv的LAM中分离出阿拉伯甘露聚糖（AM）寡糖，并将其与破伤风类毒素（TT）或来自结核分枝杆菌哈林根菌株的短期培养滤液蛋白（抗原85B（Ag85B）或一种75kDa蛋白）共价结合。不同的AM寡糖（AMOs）-蛋白结合疫苗候选物被证明具有高度免疫原性，可在兔和豚鼠中诱导针对结合物中AMOs部分的可增强的IgG反应。用结合物免疫的C57BL/6小鼠的T细胞在用PPD进行体外刺激后出现增殖。在C57BL/6小鼠中，与假免疫（仅明矾）小鼠相比，用AMOs-抗原85B结合物在明矾中进行皮下免疫提供了显著的保护作用（P<0.021），这是通过对静脉注射10(5)结核分枝杆菌H37Rv的长期存活情况估计得出的。皮下免疫后，用Eurocine L3佐剂中的AMOs-TT结合物进行鼻腔加强免疫，在经鼻内攻击10(5)毒力结核分枝杆菌哈林根菌株后，通过长期存活情况测定显示提供了高度（P<0.025）保护。这种保护水平与传统的减毒活卡介苗相当。在豚鼠中，用Eurocine L3佐剂中的AMOs-Ag85B免疫，随后用结核分枝杆菌H37Rv进行气溶胶攻击，与未免疫动物相比，导致存活率提高，肺部和脾脏的病理变化减少。
