Adjuvant Effects for Oral Immunization Provided by Recombinant Lactobacillus casei Secreting Biologically Active Murine Interleukin-1β
Adjuvant Effects for Oral Immunization Provided by Recombinant Lactobacillus casei Secreting Biologically Active Murine Interleukin-1β
复制标题
DOI：
10.1128/cvi.00337-09
复制
发表时间：
2010-01-01
影响因子：
--
通讯作者：
Igimi, Shizunobu
中科院分区：
文献类型：
--
作者：
Kajikawa, Akinobu;Masuda, Kazuya;Igimi, Shizunobu
使用乳酸菌的疫苗输送系统正在开发中，但其效率还不够。自体细胞因子，例如白细胞介素-1β (IL-1β)，是粘膜疫苗的潜在佐剂，可由重组乳酸菌提供。本研究的目的是构建和评估重组干酪乳杆菌，其产生 IL-1β 作为佐剂递送剂。使用表达/分泌载体质粒构建重组菌株，包括来自小鼠的成熟IL-1β基因。 Caco-2 细胞产生 IL-8 证实了细胞因子的生物活性。为了响应分泌 IL-1 β 的重组干酪乳杆菌，使用结扎肠环测定在体内检测 IL-6 的表达。还在体外检测到派尔氏斑细胞释放IL-6。使用热灭活肠炎沙门氏菌肠炎血清型 (SE) 与分泌 IL-1 β 的乳杆菌联合进行胃内免疫，可产生相对较高的 SE 特异性抗体。本研究证明，分泌生物活性鼠IL-1β的重组干酪乳杆菌为胃内免疫提供佐剂作用。
Vaccine delivery systems using lactic acid bacteria are under development, but their efficiency is insufficient. Autologous cytokines, such as interleukin-1 beta (IL-1 beta), are potential adjuvants for mucosal vaccines and can be provided by recombinant lactic acid bacteria. The aim of this study was the construction and evaluation of recombinant Lactobacillus casei producing IL-1 beta as an adjuvant delivery agent. The recombinant strain was constructed using an expression/secretion vector plasmid, including a mature IL-1 beta gene from mouse. The biological activity of the cytokine was confirmed by IL-8 production from Caco-2 cells. In response to the recombinant L. casei secreting IL-1 beta, expression of IL-6 was detected in vivo using a ligated-intestinal-loop assay. The release of IL-6 from Peyer's patch cells was also detected in vitro. Intragastric immunization with heat-killed Salmonella enterica serovar Enteritidis (SE) in combination with IL-1 beta-secreting lactobacilli resulted in relatively high SE-specific antibody production. In this study, it was demonstrated that recombinant L. casei secreting bioactive murine IL-1 beta provided adjuvant effects for intragastric immunization.