Engineering the microflora to vaccinate the mucosa:: serum immunoglobulin G responses and activated draining cervical lymph nodes following mucosal application of tetanus toxin fragment C-expressing lactobacilli
Engineering the microflora to vaccinate the mucosa:: serum immunoglobulin G responses and activated draining cervical lymph nodes following mucosal application of tetanus toxin fragment C-expressing lactobacilli
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DOI：
10.1046/j.1365-2567.2000.00069.x
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发表时间：
2000-08-01
期刊：
影响因子：
6.4
通讯作者：
Havenith, CEG
中科院分区：
文献类型：
--
作者：
Shaw, DM;Gaerthé, B;Havenith, CEG
通过安全、非侵入性载体（如乳酸杆菌）将抗原递送至儿科和免疫功能低下人群的粘膜相关淋巴组织，代表了对流行疫苗接种选择的关键改进。在这份报告中，我们描述了小鼠的口服和鼻腔免疫接种疫苗构建通过一个原始的系统，在乳酸杆菌中的50 000分子量（MW）的破伤风毒素（TTFC）的片段C表达为细胞内或表面暴露的蛋白质的异源基因表达。我们的数据表明L. plantarum比L.酪蛋白，并且在研究的实验条件下，表达为细胞内抗原的TTFC的递送比细胞表面表达更有效。用活的重组乳酸杆菌免疫小鼠诱导显著水平的循环TTFC特异性免疫球蛋白G（IgG），随后经鼻或经口递送疫苗菌株。此外，经鼻给药后，支气管肺泡灌洗液中诱导分泌型免疫球蛋白A（sIgA），引流淋巴结中诱导抗原特异性抗体分泌细胞和抗原特异性T细胞活化，证实了其安全粘膜给药儿科疫苗的潜力。
The delivery of antigens to mucosal-associated lymphoid tissues in paediatric and immunocompromised populations by safe, non-invasive vectors, such as commensal lactobacilli, represents a crucial improvement to prevailing vaccination options. In this report, we describe the oral and nasal immunization of mice with vaccines constructed through an original system for heterologous gene expression in Lactobacillus in which the 50 000-molecular weight (MW) fragment C of tetanus toxin (TTFC) is expressed either as an intracellular or a surface-exposed protein. Our data indicate that L. plantarum is more effective in this respect than L. casei and that, under the experimental conditions investigated, delivery of TTFC expressed as an intracellular antigen is more effective than cell-surface expression. Immunization of mice with live recombinant lactobacilli induced significant levels of circulating TTFC-specific immunoglobulin G (IgG) following nasal or oral delivery of vaccine strains. In addition, following nasal delivery, secretory immunoglobulin A (sIgA) was induced in bronchoalveolar lavage fluids, as were antigen-specific antibody-secreting cells and antigen-specific T-cell activation in draining lymph nodes, substantiating their potential for safe mucosal delivery of paediatric vaccines.