Passive immunization against murine malaria with an IgG3 monoclonal antibody.
Passive immunization against murine malaria with an IgG3 monoclonal antibody.
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DOI：
10.4049/jimmunol.132.6.3131
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发表时间：
1984-06
影响因子：
4.4
通讯作者：
W. Majarian;T. Daly;W. Weidanz;C. Long
中科院分区：
文献类型：
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作者：
W. Majarian;T. Daly;W. Weidanz;C. Long
将对约氏疟原虫17 X株免疫的BALB/c小鼠的脾细胞与P3 X63 Ag 8骨髓瘤细胞融合。在固相放射免疫分析中，1053个杂交细胞中的253个产生与破坏的17 X寄生虫反应的抗体。其中McAb 302与约氏疟原虫17 X（非致死）和17 XL（致死）变种的裂殖子反应。更重要的是，McAb 302对致死性变异体攻击感染的小鼠具有被动保护作用。在感染前用该抗体处理的小鼠在用约氏疟原虫17 XL攻击时发展出短期的低度寄生虫血症（小于0.3%）。相反，未经治疗或注射缺乏McAb 302的腹水的对照小鼠在用相同的寄生虫攻击时均死于暴发性疟疾。在其他实验中，单克隆抗体302被证明能够控制血液寄生虫水平时，给予约氏疟原虫17 XL感染的小鼠。尽管所有对照组小鼠均死亡，但单剂量McAb 302保护的小鼠最终清除了感染。无论如何进行被动免疫，给予McAb 302的小鼠对随后的约氏疟原虫17 XL攻击具有抗性，表明它们在最初的控制感染期间已经产生了显著的免疫力。McAb 302对网织红细胞寄生虫约氏疟原虫非致死性17 X株也表现出明显的被动保护活性。McAb 302的保护作用是特异性的，因为用该抗体被动免疫的小鼠在受到无关的P. vinckei攻击时死亡。McAb 302具有IgG 3同种型，并从代谢标记的约氏疟原虫两种变体的寄生虫抗原制备物中沉淀出230 kd蛋白和几个较小的多肽。它与其他鼠疟原虫种属的类似制剂不发生反应。
Spleen cells of BALB/c mice that were immune to the 17X strain of P. yoelii were fused with P3X63Ag8 myeloma cells. Two hundred fifty-three of 1053 hybrid cells produced antibodies reactive with disrupted 17X parasites in a solid phase radioimmunoassay. One of these antibodies, McAb 302, reacted with the merozoites of the 17X (nonlethal) and 17XL (lethal) variants of P. yoelii. Of greater significance, McAb 302 passively protected mice against challenge infection with the lethal variant. Mice treated with this antibody before infection developed low-grade parasitemia (less than 0.3%) of short duration when challenged with P. yoelii 17XL . In contrast, control mice that had been untreated or injected with ascites fluid lacking McAb 302 uniformly died with fulminating malaria upon challenge with the same parasite. In other experiments, McAb 302 was shown capable of controlling blood parasite levels when administered to mice with patent P. yoelii 17XL infections. Although all control mice died, mice protected with a single dose of McAb 302 ultimately cleared their infections. Regardless of how passive immunization was performed, mice given McAb 302 were resistant to subsequent challenge with P. yoelii 17XL , indicating they had developed significant immunity during their initial controlled infections. McAb 302 also showed pronounced passive protective activity against the nonlethal 17X strain of P. yoelii, which is a parasite of reticulocytes. The protection afforded by McAb 302 was specific, because mice passively immunized with this antibody died when challenged with the unrelated P. vinckei. McAb 302 was shown to possess the IgG3 isotype and precipitated a 230-kd protein plus several smaller polypeptides from metabolically labeled parasite antigen preparation derived from both variants of P. yoelii. It did not react with similar preparations of other murine plasmodial species.