Yépez Sara Huerta, Pando Rogelio Hernández, Argumedo Leopoldo Santos, Paredes Mario Vega, Cueto Angeles Hernández, Isibasi Armando, Bonilla César R González
Unidad de Investigación Médica en Inmunología e Infectologi;a, Hospital de Infectología "Dr Daniel Méndez Hernández" Centro Médico "La Raza" IMSS, Apartado Postal 15-095, Mexico City, DF 02990, Mexico.
Vaccine. 2003 Jan 17;21(5-6):566-78. doi: 10.1016/s0264-410x(02)00244-x.
An Escherichia coli strain expressing the ovalbumin (OVA) 323-329 allergenic peptide on the bacterial surface was evaluated for its ability to reduce the lung inflammatory response in mice allergic to OVA. BALB/c mice were rendered allergic by means of two intraperitoneal injections of OVA suspended in alum 5 days apart, and one intratracheal boost 1 week later. The mice were then treated with two intranasal, 1 week apart, doses of 4x10(9) E. coli-UH302 transformed with plasmids pST13 or pST13-OVA(323-339), which bear the OmpC porin from Salmonella enterica serovar Typhi or the OmpC with the OVA allergenic 323-339 amino acid sequence inserted in the external loop 5. The allergic inflammatory reaction was evaluated on day 31, finding that mice treated with E. coli-UH302-pST13-OVA reduced four to seven times perivascular and peribronchial infiltrates, mucus production, goblet cell hyperplasia and eosinophils when compared with mice treated with E. coli-UH302-pST13 or saline solution. These results were consistent with a significant decrease of IL-5 mRNA and induction of IFN-gamma mRNA in cells from bronchio-alveolar lavages (BAL). Specific serum IgE anti-OVA was also reduced, although the decrease did not reach statistical significance. These results demonstrate that the bacterial live vector bearing an allergenic peptide successfully moderated two important components of allergy, pulmonary inflammation and mucus overproduction.
对一种在细菌表面表达卵清蛋白(OVA)323 - 329过敏肽的大肠杆菌菌株进行了评估,以确定其减轻对OVA过敏小鼠肺部炎症反应的能力。通过间隔5天腹腔注射两次悬浮于明矾中的OVA,1周后进行一次气管内加强注射,使BALB/c小鼠致敏。然后,小鼠每隔1周接受两次鼻内给药,剂量为4×10⁹用质粒pST13或pST13 - OVA(323 - 339)转化的大肠杆菌 - UH302,其中pST13携带来自伤寒沙门氏菌血清型Typhi的OmpC孔蛋白,pST13 - OVA(323 - 339)在外部环5中插入了OVA过敏的323 - 339氨基酸序列的OmpC。在第31天评估过敏炎症反应,发现与用大肠杆菌 - UH302 - pST13或生理盐水处理的小鼠相比,用大肠杆菌 - UH302 - pST13 - OVA处理的小鼠的血管周围和支气管周围浸润、黏液产生、杯状细胞增生和嗜酸性粒细胞减少了4至7倍。这些结果与支气管肺泡灌洗(BAL)细胞中IL - 5 mRNA的显著降低和IFN - γ mRNA的诱导一致。特异性血清抗OVA IgE也有所降低,尽管降低未达到统计学意义。这些结果表明,携带过敏肽的细菌活载体成功地减轻了过敏的两个重要组成部分,即肺部炎症和黏液过度产生。