Intercell AG, Campus Vienna Biocenter 2, A-1030, Vienna, Austria.
Adv Exp Med Biol. 2009;655:90-117. doi: 10.1007/978-1-4419-1132-2_9.
New strategies are needed to master infectious diseases. The so-called "passive vaccination", i.e., prevention and treatment with specific antibodies, has a proven record and potential in the management of infections and entered the medical arena more than 100 years ago. Progress in the identification of specific antigens has become the hallmark in the development of novel subunit vaccines that often contain only a single immunogen, frequently proteins, derived from the microbe in order to induce protective immunity. On the other hand, the monoclonal antibody technology has enabled biotechnology to produce antibody species in unlimited quantities and at reasonable costs that are more or less identical to their human counterparts and bind with high affinity to only one specific site of a given antigen. Although, this technology has provided a robust platform for launching novel and successful treatments against a variety of devastating diseases, it is up till now only exceptionally employed in therapy of infectious diseases. Monoclonal antibodies engaged in the treatment of specific cancers seem to work by a dual mode; they mark the cancerous cells for decontamination by the immune system, but also block a function that intervenes with cell growth. The availability of the entire genome sequence of pathogens has strongly facilitated the identification of highly specific protein antigens that are suitable targets for neutralizing antibodies, but also often seem to play an important role in the microbe's life cycle. Thus, the growing repertoire of well-characterized protein antigens will open the perspective to develop monoclonal antibodies against bacterial infections, at least as last resort treatment, when vaccination and antibiotics are no options for prevention or therapy. In the following chapter we describe and compare various technologies regarding the identification of suitable target antigens and the foundation of cognate monoclonal antibodies and discuss their possible applications in the treatment of bacterial infections together with an overview of current efforts.
需要新策略来应对传染病。所谓的“被动免疫接种”，即使用特定抗体进行预防和治疗，在感染管理方面已有成效和潜力，这种方法 100 多年前就已进入医学领域。在鉴定特定抗原方面取得的进展已成为新型亚单位疫苗开发的标志，这些疫苗通常只含有一种免疫原，通常是来自微生物的蛋白质，以诱导保护性免疫。另一方面，单克隆抗体技术使生物技术能够以合理的成本无限量地生产出或多或少与其人类对应物相同的抗体种类，并且能够以高亲和力与给定抗原的仅一个特定位点结合。尽管这项技术为针对各种毁灭性疾病推出新型且成功的治疗方法提供了一个强大的平台，但到目前为止，它仅在传染病治疗中得到了特殊应用。用于治疗特定癌症的单克隆抗体似乎通过双重模式发挥作用；它们标记癌细胞，使其被免疫系统清除，但也阻止了一种干预细胞生长的功能。病原体全基因组序列的可用性极大地促进了高度特异性蛋白质抗原的鉴定，这些抗原适合作为中和抗体的靶标，而且通常在微生物的生命周期中也起着重要作用。因此，越来越多的特征明确的蛋白质抗原将为开发针对细菌感染的单克隆抗体开辟前景，至少作为最后的治疗手段，当疫苗和抗生素不能用于预防或治疗时。在下一章中，我们将描述和比较各种识别合适靶抗原和建立同源单克隆抗体的技术，并讨论它们在细菌感染治疗中的可能应用，同时概述当前的努力。
