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用表达曼氏血吸虫谷胱甘肽S-转移酶的重组卡介苗免疫小鼠后引发的中和抗体反应。

Neutralizing antibody responses elicited in mice immunized with recombinant bacillus Calmette-Guérin producing the Schistosoma mansoni glutathione S-transferase.

作者信息

Kremer L, Riveau G, Baulard A, Capron A, Locht C

机构信息

Laboratory of Host-Parasite Relations and Vaccination Strategies, INSERM Unit U167, Lille, France.

出版信息

J Immunol. 1996 Jun 1;156(11):4309-17.

PMID:8666802
Abstract

Schistosomiasis is a group of severe parasitic diseases, in humans and domestic animals, that are especially of importance in the developing world. No efficacious vaccine is currently available. However, Ab-mediated immune responses against the 28-kDa glutathione S-transferase of Schistosoma mansoni (Sm28GST) appear to be involved in protection. This Ag was produced in recombinant Mycobacterium bovis bacillus Calmette-Guérin (BCG). The recombinant protein bound glutathione and expressed enzymatic activity, indicating that the active site of Sm28GST was folded properly. Single i.v., i.p., s.c., or intranasal immunizations with rBCG in BALB/c mice resulted in significant anti-SM28GST Ab responses, which were enhanced by a booster dose. The Ab responses remained high for at least 1 yr after immunization. Analyses of the isotype profiles indicated that i.v. immunized mice produced high titers of anti-Sm28GST IgG2a, and less IgG2b and IgG1. Mice immunized by the s.c. route initially also produced high levels of IgG2a and low titers of IgG1 and IgG2b, but the titers of the latter two isotypes increased gradually thereafter, tending toward a mixed profile. Intraperitoneal immunization provided a mixed profile directly after the first administration. High titers of anti-Sm28GST Abs also corresponded to high levels of neutralization of the enzymatic activity. These results indicate that rBCG induces strong IgG1, IgG2a, and IgG2b, and neutralizing Ab responses against Sm28GST, which has been found to correlate with protection against S. mansoni in humans.

摘要

血吸虫病是一组严重的寄生虫病,可感染人类和家畜,在发展中世界尤为重要。目前尚无有效的疫苗。然而,针对曼氏血吸虫28 kDa谷胱甘肽S - 转移酶(Sm28GST)的抗体介导的免疫反应似乎与保护作用有关。这种抗原是在重组牛分枝杆菌卡介苗(BCG)中产生的。重组蛋白结合谷胱甘肽并表现出酶活性,表明Sm28GST的活性位点折叠正确。在BALB/c小鼠中,通过静脉内、腹腔内、皮下或鼻内单次接种rBCG可产生显著的抗SM28GST抗体反应,加强剂量可增强这种反应。免疫后抗体反应至少1年内保持高水平。对抗体亚型谱的分析表明,静脉内免疫的小鼠产生高滴度的抗Sm28GST IgG2a,而IgG2b和IgG1较少。皮下途径免疫的小鼠最初也产生高水平的IgG2a以及低滴度的IgG1和IgG2b,但后两种亚型的滴度随后逐渐增加,趋向于混合谱。腹腔内免疫在首次给药后直接产生混合谱。高滴度的抗Sm28GST抗体也对应高水平的酶活性中和。这些结果表明,rBCG诱导针对Sm28GST的强烈IgG1、IgG2a和IgG2b以及中和抗体反应,已发现这与人类对曼氏血吸虫的保护作用相关。

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