Kajikawa Akinobu, Masuda Kazuya, Katoh Mitsunori, Igimi Shizunobu
Division of Biomedical Food Research, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan.
Clin Vaccine Immunol. 2010 Jan;17(1):43-8. doi: 10.1128/CVI.00337-09. Epub 2009 Nov 18.
Vaccine delivery systems using lactic acid bacteria are under development, but their efficiency is insufficient. Autologous cytokines, such as interleukin-1beta (IL-1beta), 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-1beta as an adjuvant delivery agent. The recombinant strain was constructed using an expression/secretion vector plasmid, including a mature IL-1beta 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-1beta, 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-1beta-secreting lactobacilli resulted in relatively high SE-specific antibody production. In this study, it was demonstrated that recombinant L. casei secreting bioactive murine IL-1beta provided adjuvant effects for intragastric immunization.
利用乳酸菌的疫苗递送系统正在研发中,但其效率尚不足。自体细胞因子,如白细胞介素-1β(IL-1β),是黏膜疫苗的潜在佐剂,可由重组乳酸菌提供。本研究的目的是构建并评估产IL-1β的重组干酪乳杆菌作为佐剂递送载体。使用包含小鼠成熟IL-1β基因的表达/分泌载体质粒构建重组菌株。通过Caco-2细胞产生IL-8来确认细胞因子的生物学活性。针对分泌IL-1β的重组干酪乳杆菌,使用结扎肠袢试验在体内检测到IL-6的表达。在体外也检测到派伊尔结细胞释放IL-6。用热灭活的肠炎沙门氏菌肠炎血清型(SE)联合分泌IL-1β的乳杆菌进行胃内免疫,可产生相对较高的SE特异性抗体。在本研究中,证明了分泌具有生物活性的鼠IL-1β的重组干酪乳杆菌为胃内免疫提供了佐剂效应。