An anti-idiotype vaccine against experimental schistosomiasis
An anti-idiotype vaccine against experimental schistosomiasis
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一种针对实验性血吸虫病的抗独特型疫苗
DOI：
10.1038/316074a0
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发表时间：
1985
期刊：
影响因子：
64.8
通讯作者：
André Capron
中科院分区：
文献类型：
--
作者：
J. Grzych;Monique Capron;P. Lambert;Colette Dissous;S. Torres;André Capron
血吸虫病是一种人类寄生虫感染疾病，在热带国家广泛传播，但迄今为止尚未得到控制。我们一直从免疫学的角度来解决这个问题。我们之前报道过 1 抗曼氏血吸虫的大鼠单克隆 IgG2a 抗体的生产，该抗体在嗜酸性粒细胞存在的情况下对血吸虫表现出显着的细胞毒性，并且通过在幼稚大鼠中被动转移而表现出高度的保护作用。这种抗体 IPLSm1 被证明可以特异性结合血吸虫膜靶抗原，该抗原被定义为相对分子质量为 38,000 (38K)2 的糖蛋白，该抗原在包括 man3 在内的各种动物物种的血吸虫感染中具有强免疫原性。尽管从理论上讲，38K 蛋白是抗血吸虫病潜在疫苗的绝佳候选者，但 IPLSm1 识别的表位的聚糖性质限制了其通过 DNA 重组技术的生产。此外，还表明，38K 分子与保护性抗体一起能够诱导产生阻断性 IgG2c 抗体，该抗体在体外和体内均抑制 IPLSml 的功能特性。因此，根据杰恩的网络理论5，我们考虑了另一种方法，即使用抗独特型抗体进行免疫的可能性。在本研究中，产生了针对 IPLSm1 (AB1) 的大鼠单克隆抗独特型抗体。根据抗独特型抗体 (AB2) 抑制放射性碘标记的 AB1 与其 38K 靶抗原结合的能力来选择。用纯化的 AB2 制剂免疫的幼稚 LOU 大鼠的血清含有特异性抗血吸虫抗体 (AB3)，该抗体与 38K 结合。在大鼠嗜酸性粒细胞存在的情况下，AB3 抗体对血吸虫具有强烈的细胞毒性，并通过被动转移提供高度显着的保护。最重要的是，用 AB2 免疫的大鼠表现出对攻击性感染的显着保护（50-80%）。
Schistosomiasis is a parasitic infection of man which is widespread in tropical countries, and which so far has resisted attempts at control. We have been approaching the problem from an immunological angle. We have previously reported1 the production of a rat monoclonal IgG2a antibody against Schistosoma mansoni which exhibits marked cytoxicity for schistosomula in the presence of eosinophils and a high degree of protection by passive transfer in naive rats. This antibody, IPLSm1, was shown to bind specifically to a schistosomulum membrane target antigen defined as a glycoprotein of relative molecular mass 38,000 (38K)2, which is strongly immunogenic in schistosome infection of various animal species including man3. Although theoretically the 38K protein represents an excellent candidate for a potential vaccine against schistosomiasis, the glycanic nature of the epitope recognized by IPLSm1 limits its production by DNA recombinant technology. It was, moreover, shown that, together with protective antibodies, the 38K molecule was able to induce the production of blocking IgG2c antibodies that inhibit the functional properties of IPLSml both in vitro and in vivo4. Therefore, following Jerne's network theory5, we considered an alternative approach, the possibility of immunization using anti-idiotype antibodies. In the present study, rat monoclonal anti-idiotype antibodies were produced against IPLSm1 (AB1). Anti-idiotype antibodies (AB2) were selected by their capacity to inhibit the binding of radioiodinated AB1, to its 38K target antigen. Sera from naive LOU rats immunized with a purified AB2 preparation contained specific anti-schistosome antibodies (AB3), which bound to 38K. AB3 antibodies were strongly cytotoxic for schistosomula in the presence of rat eosinophils and conferred highly significant protection by passive transfer. Most importantly, rats immunized with AB2 demonstrated marked protection (50–80%) to a challenge infection.