A novel M cell-specific carbohydrate-targeted mucosal vaccine effectively induces antigen-specific immune responses.
A novel M cell-specific carbohydrate-targeted mucosal vaccine effectively induces antigen-specific immune responses.
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DOI：
10.1084/jem.20070607
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发表时间：
2007-11-26
期刊：
影响因子：
--
通讯作者：
Kiyono H
中科院分区：
文献类型：
--
作者：
Nochi T;Yuki Y;Matsumura A;Mejima M;Terahara K;Kim DY;Fukuyama S;Iwatsuki-Horimoto K;Kawaoka Y;Kohda T;Kozaki S;Igarashi O;Kiyono H
粘膜摄取和吸入的抗原被派伊尔集合淋巴结或鼻咽相关淋巴组织的滤泡相关上皮中的膜细胞或微折叠细胞（M细胞）摄取。我们建立了一种新的M细胞特异性单克隆抗体（mAb NKM 16-2-4）作为M细胞靶向粘膜疫苗的载体。mAb NKM 16-2-4也与最近发现的绒毛M细胞反应，但不与上皮细胞或杯状细胞反应。口服破伤风类毒素（TT）或肉毒杆菌类毒素（BT）结合的NKM 16-2-4，以及粘膜佐剂霍乱毒素，诱导高水平，抗原特异性血清免疫球蛋白（IG）G和粘膜伊加反应。此外，BT缀合的NKM 16-2-4的口服疫苗制剂诱导针对肉毒杆菌毒素致死攻击的保护性免疫。NKM 16-2-4的表位分析显示对含α（1，2）-岩藻糖的碳水化合物部分具有特异性，在缺乏唾液酸的条件下反应性增强。这表明NKM 16-2-4将α（1，2）-岩藻糖基化M细胞与含有丰富唾液酸的杯状细胞（邻近α（1，2）岩藻糖部分）和非α（1，2）-岩藻糖基化上皮细胞区分开来。使用NKM 16-2-4将疫苗抗原靶向M细胞特异性碳水化合物部分是开发高效粘膜疫苗的新策略。
Mucosally ingested and inhaled antigens are taken up by membranous or microfold cells (M cells) in the follicle-associated epithelium of Peyer's patches or nasopharynx-associated lymphoid tissue. We established a novel M cell–specific monoclonal antibody (mAb NKM 16–2-4) as a carrier for M cell–targeted mucosal vaccine. mAb NKM 16–2-4 also reacted with the recently discovered villous M cells, but not with epithelial cells or goblet cells. Oral administration of tetanus toxoid (TT)– or botulinum toxoid (BT)–conjugated NKM 16–2-4, together with the mucosal adjuvant cholera toxin, induced high-level, antigen-specific serum immunoglobulin (Ig) G and mucosal IgA responses. In addition, an oral vaccine formulation of BT-conjugated NKM 16–2-4 induced protective immunity against lethal challenge with botulinum toxin. An epitope analysis of NKM 16–2-4 revealed specificity to an α(1,2)-fucose–containing carbohydrate moiety, and reactivity was enhanced under sialic acid–lacking conditions. This suggests that NKM 16–2-4 distinguishes α(1,2)-fucosylated M cells from goblet cells containing abundant sialic acids neighboring the α(1,2) fucose moiety and from non-α(1,2)-fucosylated epithelial cells. The use of NKM 16–2-4 to target vaccine antigens to the M cell–specific carbohydrate moiety is a new strategy for developing highly effective mucosal vaccines.
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影响因子：
4.4
作者：
Wang, XH;Hone, DM;Pascual, DW
通讯作者：
Pascual, DW
DOI：
10.1073/pnas.161204098
发表时间：
2001-07-31
影响因子：
11.1
作者：
Wu, YP;Wang, XH;Pascual, DW
通讯作者：
Pascual, DW
影响因子：
15.3
作者：
Xu-Amano, J;Kiyono, H;Jackson, R J;Staats, H F;Fujihashi, K;Burrows, P D;Elson, C O;Pillai, S;McGhee, J R
通讯作者：
McGhee, J R
影响因子：
15.3
作者：
Bonifaz, LC;Bonnyay, DP;Charalambous, A;Darguste, DI;Fujii, SI;Soares, H;Brimnes, MK;Moltedo, B;Moran, TM;Steinman, RM
通讯作者：
Steinman, RM
影响因子：
15.9
作者：
LOOK, AT;ASHMUN, RA;PEIPER, SC
通讯作者：
PEIPER, SC