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通过抗独特型疫苗接种在体内预防蓖麻毒素中毒

Protection against ricin intoxication in vivo by anti-idiotype vaccination.

作者信息

Chanh T C, Hewetson J F

机构信息

Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, TX 78228, USA.

出版信息

Vaccine. 1995 Apr;13(5):479-85. doi: 10.1016/0264-410x(94)00020-n.

Abstract

A BALB/c murine anti-ricin monoclonal antibody (mAb BG11-G2, IgG1K), was recently isolated and shown to passively protect syngeneic mice against ricin intoxication in vivo. New Zealand White rabbit polyclonal anti-idiotype (anti-Id) antibodies were raised to BG11-G2 anti-ricin mAb, and rendered specific by repeated absorption over agarose normal mouse immunoglobulin (Ig). The absorbed rabbit anti-Id antibodies lost reactivity to normal mouse Ig and to a BALB/c anti-T-2 mycotoxin IgG1K mAb (HD11), but remained reactive with BG11-G2 anti-ricin mAb. The rabbit anti-Id inhibited the binding of BG11-G2 mAb to ricin-coated wells, and elicited a specific and protective anti-ricin antibody response in naive BALB/c mice. Whereas all mice vaccinated with a control rabbit anti-Id antibody preparation died from in vivo ricin challenges, mice immunized with the rabbit anti-Id specific for BG11-G2 mAb were protected to various degrees. All mice vaccinated with rabbit anti-Id to BG11-G2 and challenged with ricin doses of 35 and 50 micrograms kg-1 body weight died from the challenge; however, a delay in the elapsed time between ricin administration and death was observed in these mice as compared to that of the control anti-Id-immune mice. Five of seven mice vaccinated with the rabbit anti-Id to BG11-G2 and subsequently challenged in vivo with a ricin dose of 20 micrograms kg-1 body weight survived the lethal in vivo ricin challenge, whereas all the control mice died.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

最近分离出一种BALB/c小鼠抗蓖麻毒素单克隆抗体(单克隆抗体BG11-G2,IgG1K),并证明其能在体内被动保护同基因小鼠免受蓖麻毒素中毒。用BG11-G2抗蓖麻毒素单克隆抗体制备了新西兰白兔多克隆抗独特型(抗Id)抗体,并通过在琼脂糖正常小鼠免疫球蛋白(Ig)上反复吸附使其具有特异性。吸附后的兔抗Id抗体失去了与正常小鼠Ig和BALB/c抗T-2霉菌毒素IgG1K单克隆抗体(HD11)的反应性,但仍与BG11-G2抗蓖麻毒素单克隆抗体反应。兔抗Id抑制了BG11-G2单克隆抗体与包被蓖麻毒素的孔的结合,并在未免疫的BALB/c小鼠中引发了特异性的保护性抗蓖麻毒素抗体反应。所有接种对照兔抗Id抗体制备物的小鼠都死于体内蓖麻毒素攻击,而用针对BG11-G2单克隆抗体的兔抗Id免疫的小鼠则受到不同程度的保护。所有接种针对BG11-G2的兔抗Id并接受体重35和50微克/千克剂量蓖麻毒素攻击的小鼠都死于攻击;然而,与对照抗Id免疫小鼠相比,这些小鼠在蓖麻毒素给药和死亡之间的时间间隔有所延迟。七只接种针对BG11-G2的兔抗Id并随后接受体重20微克/千克剂量蓖麻毒素体内攻击的小鼠中有五只在致命的体内蓖麻毒素攻击中存活下来,而所有对照小鼠都死亡。(摘要截短至250字)

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