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Epitope maps of the Escherichia coli heat-labile toxin B subunit for development of a synthetic oral vaccine.

机译:大肠杆菌热不稳定毒素B亚基的抗原决定簇图谱,用于开发合成口服疫苗。

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Linear B- and T-cell epitopes spanning all 103 amino acids of the Escherichia coli heat-labile toxin B subunit (LT-B) were assessed in mice orally immunized with native LT or with recombinant Salmonella enteritidis expressing LT-B. Oral administration of native LT induced mucosal immunoglobulin A (IgA) antibodies reactive with an epitope at residues 85 to 91, while IgA induced by recombinant Salmonella LT-B reacted with an epitope at residues 36 to 44. Serum IgG anti-LT-B antibodies from mice orally immunized with either LT or with recombinant Salmonella LT-B were directed to both epitopes. A single T-cell epitope spanning residues 34 to 42 was identified by T-cell proliferative and cytokine responses. When a 20-mer peptide (residues 26 to 45) with B- and T-cell epitopes was given orally to BALB/c (H-2(d)) and B10 congenic (I-A(d), I-A(b), and I-A(k)) mice, significant fecal IgA and serum IgG anti-LT-B antibodies were induced. The peptide also induced LT-B-specific T-cell proliferative responses in these mice. Orally administered LT-B peptide (residues 26 to 45) induced a cytokine profile indicative of both T helper 1- and 2-type cells. The remarkable immunogenicity of this 20-mer peptide makes it a candidate for a vaccine to protect against enterotoxigenic E. coli.
机译:在口服天然LT或表达LT-B的重组肠炎沙门氏菌免疫的小鼠中,评估了跨越大肠杆菌热不稳定毒素B亚基(LT-B)的所有103个氨基酸的线性B细胞和T细胞表位。口服天然LT诱导的粘膜免疫球蛋白A(IgA)抗体与第85-91位残基的表位反应,而重组沙门氏菌LT-B诱导的IgA与第36-44位残基的表位反应。 LT或重组沙门氏菌LT-B口服免疫的小鼠体内的两种抗原均针对两个表位。通过T细胞增殖和细胞因子反应鉴定出跨越残基34至42的单个T细胞表位。将具有B细胞和T细胞表位的20-mer肽(26至45位残基)口服给予BALB / c(H-2(d))和B10同基因(IA(d),IA(b)和IA(k))小鼠,重要的粪便IgA和血清IgG抗LT-B抗体被诱导。该肽还诱导了这些小鼠的LT-B特异性T细胞增殖反应。口服给予的LT-B肽(第26至45位残基)诱导了细胞因子谱,表明T辅助1型和2型细胞。这种20-mer肽具有非凡的免疫原性,使其成为预防肠毒素大肠杆菌的疫苗的候选者。

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